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113 Great Research Paper Topics

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One of the hardest parts of writing a research paper can be just finding a good topic to write about. Fortunately we've done the hard work for you and have compiled a list of 113 interesting research paper topics. They've been organized into ten categories and cover a wide range of subjects so you can easily find the best topic for you.

In addition to the list of good research topics, we've included advice on what makes a good research paper topic and how you can use your topic to start writing a great paper.

What Makes a Good Research Paper Topic?

Not all research paper topics are created equal, and you want to make sure you choose a great topic before you start writing. Below are the three most important factors to consider to make sure you choose the best research paper topics.

#1: It's Something You're Interested In

A paper is always easier to write if you're interested in the topic, and you'll be more motivated to do in-depth research and write a paper that really covers the entire subject. Even if a certain research paper topic is getting a lot of buzz right now or other people seem interested in writing about it, don't feel tempted to make it your topic unless you genuinely have some sort of interest in it as well.

#2: There's Enough Information to Write a Paper

Even if you come up with the absolute best research paper topic and you're so excited to write about it, you won't be able to produce a good paper if there isn't enough research about the topic. This can happen for very specific or specialized topics, as well as topics that are too new to have enough research done on them at the moment. Easy research paper topics will always be topics with enough information to write a full-length paper.

Trying to write a research paper on a topic that doesn't have much research on it is incredibly hard, so before you decide on a topic, do a bit of preliminary searching and make sure you'll have all the information you need to write your paper.

#3: It Fits Your Teacher's Guidelines

Don't get so carried away looking at lists of research paper topics that you forget any requirements or restrictions your teacher may have put on research topic ideas. If you're writing a research paper on a health-related topic, deciding to write about the impact of rap on the music scene probably won't be allowed, but there may be some sort of leeway. For example, if you're really interested in current events but your teacher wants you to write a research paper on a history topic, you may be able to choose a topic that fits both categories, like exploring the relationship between the US and North Korea. No matter what, always get your research paper topic approved by your teacher first before you begin writing.

113 Good Research Paper Topics

Below are 113 good research topics to help you get you started on your paper. We've organized them into ten categories to make it easier to find the type of research paper topics you're looking for.

Arts/Culture

Discuss the main differences in art from the Italian Renaissance and the Northern Renaissance .
Analyze the impact a famous artist had on the world.
How is sexism portrayed in different types of media (music, film, video games, etc.)? Has the amount/type of sexism changed over the years?
How has the music of slaves brought over from Africa shaped modern American music?
How has rap music evolved in the past decade?
How has the portrayal of minorities in the media changed?

Current Events

What have been the impacts of China's one child policy?
How have the goals of feminists changed over the decades?
How has the Trump presidency changed international relations?
Analyze the history of the relationship between the United States and North Korea.
What factors contributed to the current decline in the rate of unemployment?
What have been the impacts of states which have increased their minimum wage?
How do US immigration laws compare to immigration laws of other countries?
How have the US's immigration laws changed in the past few years/decades?
How has the Black Lives Matter movement affected discussions and view about racism in the US?
What impact has the Affordable Care Act had on healthcare in the US?
What factors contributed to the UK deciding to leave the EU (Brexit)?
What factors contributed to China becoming an economic power?
Discuss the history of Bitcoin or other cryptocurrencies (some of which tokenize the S&P 500 Index on the blockchain) .
Do students in schools that eliminate grades do better in college and their careers?
Do students from wealthier backgrounds score higher on standardized tests?
Do students who receive free meals at school get higher grades compared to when they weren't receiving a free meal?
Do students who attend charter schools score higher on standardized tests than students in public schools?
Do students learn better in same-sex classrooms?
How does giving each student access to an iPad or laptop affect their studies?
What are the benefits and drawbacks of the Montessori Method ?
Do children who attend preschool do better in school later on?
What was the impact of the No Child Left Behind act?
How does the US education system compare to education systems in other countries?
What impact does mandatory physical education classes have on students' health?
Which methods are most effective at reducing bullying in schools?
Do homeschoolers who attend college do as well as students who attended traditional schools?
Does offering tenure increase or decrease quality of teaching?
How does college debt affect future life choices of students?
Should graduate students be able to form unions?

What are different ways to lower gun-related deaths in the US?
How and why have divorce rates changed over time?
Is affirmative action still necessary in education and/or the workplace?
Should physician-assisted suicide be legal?
How has stem cell research impacted the medical field?
How can human trafficking be reduced in the United States/world?
Should people be able to donate organs in exchange for money?
Which types of juvenile punishment have proven most effective at preventing future crimes?
Has the increase in US airport security made passengers safer?
Analyze the immigration policies of certain countries and how they are similar and different from one another.
Several states have legalized recreational marijuana. What positive and negative impacts have they experienced as a result?
Do tariffs increase the number of domestic jobs?
Which prison reforms have proven most effective?
Should governments be able to censor certain information on the internet?
Which methods/programs have been most effective at reducing teen pregnancy?
What are the benefits and drawbacks of the Keto diet?
How effective are different exercise regimes for losing weight and maintaining weight loss?
How do the healthcare plans of various countries differ from each other?
What are the most effective ways to treat depression ?
What are the pros and cons of genetically modified foods?
Which methods are most effective for improving memory?
What can be done to lower healthcare costs in the US?
What factors contributed to the current opioid crisis?
Analyze the history and impact of the HIV/AIDS epidemic .
Are low-carbohydrate or low-fat diets more effective for weight loss?
How much exercise should the average adult be getting each week?
Which methods are most effective to get parents to vaccinate their children?
What are the pros and cons of clean needle programs?
How does stress affect the body?
Discuss the history of the conflict between Israel and the Palestinians.
What were the causes and effects of the Salem Witch Trials?
Who was responsible for the Iran-Contra situation?
How has New Orleans and the government's response to natural disasters changed since Hurricane Katrina?
What events led to the fall of the Roman Empire?
What were the impacts of British rule in India ?
Was the atomic bombing of Hiroshima and Nagasaki necessary?
What were the successes and failures of the women's suffrage movement in the United States?
What were the causes of the Civil War?
How did Abraham Lincoln's assassination impact the country and reconstruction after the Civil War?
Which factors contributed to the colonies winning the American Revolution?
What caused Hitler's rise to power?
Discuss how a specific invention impacted history.
What led to Cleopatra's fall as ruler of Egypt?
How has Japan changed and evolved over the centuries?
What were the causes of the Rwandan genocide ?

Why did Martin Luther decide to split with the Catholic Church?
Analyze the history and impact of a well-known cult (Jonestown, Manson family, etc.)
How did the sexual abuse scandal impact how people view the Catholic Church?
How has the Catholic church's power changed over the past decades/centuries?
What are the causes behind the rise in atheism/ agnosticism in the United States?
What were the influences in Siddhartha's life resulted in him becoming the Buddha?
How has media portrayal of Islam/Muslims changed since September 11th?

Science/Environment

How has the earth's climate changed in the past few decades?
How has the use and elimination of DDT affected bird populations in the US?
Analyze how the number and severity of natural disasters have increased in the past few decades.
Analyze deforestation rates in a certain area or globally over a period of time.
How have past oil spills changed regulations and cleanup methods?
How has the Flint water crisis changed water regulation safety?
What are the pros and cons of fracking?
What impact has the Paris Climate Agreement had so far?
What have NASA's biggest successes and failures been?
How can we improve access to clean water around the world?
Does ecotourism actually have a positive impact on the environment?
Should the US rely on nuclear energy more?
What can be done to save amphibian species currently at risk of extinction?
What impact has climate change had on coral reefs?
How are black holes created?
Are teens who spend more time on social media more likely to suffer anxiety and/or depression?
How will the loss of net neutrality affect internet users?
Analyze the history and progress of self-driving vehicles.
How has the use of drones changed surveillance and warfare methods?
Has social media made people more or less connected?
What progress has currently been made with artificial intelligence ?
Do smartphones increase or decrease workplace productivity?
What are the most effective ways to use technology in the classroom?
How is Google search affecting our intelligence?
When is the best age for a child to begin owning a smartphone?
Has frequent texting reduced teen literacy rates?

How to Write a Great Research Paper

Even great research paper topics won't give you a great research paper if you don't hone your topic before and during the writing process. Follow these three tips to turn good research paper topics into great papers.

#1: Figure Out Your Thesis Early

Before you start writing a single word of your paper, you first need to know what your thesis will be. Your thesis is a statement that explains what you intend to prove/show in your paper. Every sentence in your research paper will relate back to your thesis, so you don't want to start writing without it!

As some examples, if you're writing a research paper on if students learn better in same-sex classrooms, your thesis might be "Research has shown that elementary-age students in same-sex classrooms score higher on standardized tests and report feeling more comfortable in the classroom."

If you're writing a paper on the causes of the Civil War, your thesis might be "While the dispute between the North and South over slavery is the most well-known cause of the Civil War, other key causes include differences in the economies of the North and South, states' rights, and territorial expansion."

#2: Back Every Statement Up With Research

Remember, this is a research paper you're writing, so you'll need to use lots of research to make your points. Every statement you give must be backed up with research, properly cited the way your teacher requested. You're allowed to include opinions of your own, but they must also be supported by the research you give.

#3: Do Your Research Before You Begin Writing

You don't want to start writing your research paper and then learn that there isn't enough research to back up the points you're making, or, even worse, that the research contradicts the points you're trying to make!

Get most of your research on your good research topics done before you begin writing. Then use the research you've collected to create a rough outline of what your paper will cover and the key points you're going to make. This will help keep your paper clear and organized, and it'll ensure you have enough research to produce a strong paper.

What's Next?

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These recommendations are based solely on our knowledge and experience. If you purchase an item through one of our links, PrepScholar may receive a commission.

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Christine graduated from Michigan State University with degrees in Environmental Biology and Geography and received her Master's from Duke University. In high school she scored in the 99th percentile on the SAT and was named a National Merit Finalist. She has taught English and biology in several countries.

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301+ Research Topic Examples For Students [Updated 2024]

Embarking on a research journey is a crucial aspect of academic growth for students. Selecting the right research topic is like choosing the key that unlocks the door to a world of academic exploration and discovery. In this blog, we will delve into the importance of choosing a relevant research topic for students, explore various considerations for topic selection, and provide research topic examples for students across different academic domains.

General Considerations for Selecting Research Topics

Table of Contents

Personal Interest

Identifying and pursuing personal interests is a fundamental aspect of selecting a research topic. When students choose a subject they are passionate about, the research process becomes an exciting journey rather than a mundane task. This can involve reflecting on hobbies, current events, or personal experiences that spark curiosity.

For example, a student interested in technology might explore the impact of artificial intelligence on society, delving into its implications for employment, ethics, and social dynamics.

Academic Relevance

Aligning the research topic with academic goals is essential for maximizing the learning experience. Students should consider how their chosen topic relates to their coursework and future career aspirations.

For instance, a psychology student might explore the effects of social media on mental health, connecting the research to their academic background and potential career path.

301+ Research Topic Examples for Students

Science and technology.

Quantum computing and its potential applications
Cybersecurity threats in the age of digital transformation
The role of nanotechnology in medicine
Impacts of 5G technology on communication networks
Sustainable practices in IT: Green computing
Robotics in healthcare: Current trends and future prospects
Ethical considerations in genetic engineering
Augmented reality and its applications in education
The future of space exploration: Mars colonization
Big data analytics for predicting disease outbreaks

Social Sciences

Impact of social media on political activism
Cultural appropriation in the fashion industry
Influence of family structure on child development
The psychology of decision-making in consumer behavior
Social implications of virtual reality experiences
Intersectionality and its role in social justice
Effects of climate change on migration patterns
Social perceptions of mental health disorders
Online communities and their impact on social isolation
Gender roles in contemporary society: Breaking stereotypes

Health and Medicine

The microbiome and its role in human health
Investigating alternative therapies for chronic pain management
Impact of sleep deprivation on cognitive function
Precision medicine: Tailoring treatments based on genetics
The role of gut health in immune system function
Telemedicine: Accessibility and effectiveness
Public health interventions for reducing obesity rates
Challenges in mental health care for marginalized communities
Exploring the link between diet and mental health
Vaccine hesitancy and its implications for public health
The effectiveness of project-based learning in STEM education
Assessing the impact of standardized testing on student stress
Inclusive education for children with learning disabilities
The role of teacher-student relationships in academic success
Gamification in education: Engaging students through games
Evaluating the effectiveness of online education platforms
School policies and their impact on LGBTQ+ students
Benefits and challenges of bilingual education
The role of arts education in fostering creativity
Technology integration in the classroom: Enhancing learning experiences

Business and Economics

The gig economy: Implications for workers and businesses
Corporate social responsibility and consumer behavior
Impact of e-commerce on traditional retail businesses
Cryptocurrency: Risks and opportunities in the financial market
Strategies for sustainable business practices
Workplace diversity and its impact on organizational performance
The role of emotional intelligence in leadership
Global economic disparities and their consequences
Challenges and opportunities for small businesses in a digital era
Consumer trust in online reviews and its influence on purchasing decisions

Environmental Science

The role of forests in carbon sequestration
Impact of plastic pollution on marine ecosystems
Sustainable agriculture practices for food security
Biodiversity conservation in urban environments
The effects of climate change on migratory patterns of animals
Renewable energy policies and their effectiveness
Pollution in urban areas: Assessing air and water quality
The role of wetlands in flood control and water purification
Conservation strategies for endangered species
Environmental education and its impact on eco-friendly behaviors

Political Science

The role of social media in shaping political opinions
Electoral systems and their impact on representation
International relations: Diplomacy and conflict resolution
Political polarization and its consequences for democracy
Human rights violations in conflict zones
The influence of lobbying on public policy decisions
Immigration policies and their societal implications
The role of women in politics: Breaking the glass ceiling
Cyber warfare and its impact on national security
Political ideologies and their evolution over time
The impact of childhood trauma on adult mental health
Cross-cultural differences in perception and cognition
Exploring the link between personality traits and career choices
Cognitive biases and decision-making errors
Psychosocial factors influencing addiction recovery
The role of positive psychology in promoting well-being
Effects of social media on body image and self-esteem
Sleep disorders and their impact on mental health
Stereotype threat in academic settings
The psychology of forgiveness and its therapeutic benefits
Social mobility and its relation to economic inequality
Social networks and their influence on career opportunities
The impact of incarceration on families and communities
Youth subcultures and their role in identity formation
The digital divide: Access to technology and social inequality
Social movements: Causes, dynamics, and outcomes
The role of religion in shaping social attitudes
Aging populations: Challenges and opportunities
Urbanization and its effects on community dynamics
Social stratification and its consequences for societal cohesion
Reevaluating historical events from multiple perspectives
The impact of colonialism on indigenous cultures
Women’s suffrage movements around the world
Historical analysis of economic recessions and recoveries
Revolutionary movements and their effects on society
The role of propaganda in shaping historical narratives
Cultural exchange and influence in ancient civilizations
Historical roots of current geopolitical conflicts
Technological advancements and their impact on historical eras
The legacy of historical figures in shaping modern ideologies

Literature and Language

The portrayal of gender roles in classic literature
The influence of folklore on contemporary literature
Linguistic diversity in multicultural societies
The evolution of language: Impact of technology and globalization
Analysis of dystopian literature and its reflection on society
Comparative study of literary movements across cultures
The role of literature in fostering empathy and understanding
The representation of mental health in literature
Translation challenges in preserving cultural nuances
Language acquisition in multilingual environments

Anthropology

Cultural practices surrounding death and mourning rituals
Studying indigenous communities and cultural preservation
Human adaptation to environmental changes throughout history
Impact of globalization on traditional cultural practices
Evolutionary perspectives on human behavior
Cultural relativism and its role in anthropological research
Ethnographic study of modern subcultures
Rituals and ceremonies in different world cultures
Social organization and kinship systems in tribal societies
Ethical considerations in anthropological fieldwork

Art and Design

The role of art therapy in mental health treatment
Influences of cultural movements on contemporary art
Exploring the intersection of technology and visual arts
Impact of public art installations on urban environments
Analysis of symbolism in Renaissance art
The evolution of graphic design in the digital age
Environmental art: Conveying messages about sustainability
Fashion trends and their cultural implications
The psychology of color in design and marketing
The relationship between art and political activism
Ethical implications of emerging technologies
Existentialist perspectives on human freedom and responsibility
Metaethics: Exploring the nature of ethical statements
Epistemological analysis of artificial intelligence
Philosophical perspectives on the concept of time
The relationship between mind and body: Dualism vs. monism
The philosophy of education: Examining different approaches
Environmental ethics and responsibilities
Political philosophy: The concept of justice
Comparative analysis of Eastern and Western philosophical traditions

Music and Performing Arts

Impact of technology on the music industry
Cultural influences on musical genres
The role of music in film: Emotional impact and storytelling
The evolution of dance as a cultural expression
Representation of social issues in theater productions
Music therapy for mental health and well-being
The intersection of music and activism
Cultural appropriation in the performing arts
Influences of globalization on traditional music styles
Experimental approaches in contemporary performing arts

Communications and Media Studies

The impact of fake news on public opinion
Representation of diversity in the media
Social media influencers and their influence on consumer behavior
The role of media in shaping political narratives
Online privacy concerns in the era of digital communication
The evolution of advertising in the age of streaming services
Investigating media bias in news reporting
Ethical considerations in photojournalism
Media literacy education: Promoting critical thinking skills
The future of journalism in the digital age

Criminal Justice and Law

The effectiveness of restorative justice programs
Police-community relations: Building trust and accountability
Cybercrime and the challenges of law enforcement
Juvenile justice reform: Balancing punishment and rehabilitation
Police Brutality and Accountability
Cybercrime and Digital Forensics
Bail Reform and Pretrial Detention
Human rights violations in prisons: Challenges and solutions
Legal implications of emerging surveillance technologies
The impact of criminalization on marginalized communities

Linguistics

The evolution of language: From ancient to modern times
Sociolinguistics: Language variation in different social contexts
Bilingualism and its cognitive effects on language processing
Analyzing language change through historical linguistics
Phonetics and phonology: Exploring sound patterns in languages
Syntax and sentence structure across diverse languages
The role of language in shaping cultural identities
Linguistic relativity: The influence of language on thought
Computational linguistics: Applications in natural language processing

Geography and Urban Studies

Urbanization and its impact on local ecosystems
Geopolitical implications of natural resource distribution
Sustainable urban planning for future cities
Environmental justice in urban areas
Exploring the dynamics of rural-urban migration
Geographic Information Systems (GIS) applications in urban studies
Impact of climate change on coastal communities
Urban transportation systems: Challenges and innovations
Cultural geography: Understanding the relationship between people and place
Historical analysis of urban development in different regions
The economic impact of global pandemics
Income inequality and its effects on economic growth
The role of central banks in monetary policy
Economic consequences of automation and artificial intelligence
Behavioral economics: Understanding decision-making processes
The economics of healthcare systems around the world
The gig economy and its implications for labor markets
Trade policies and their impact on international relations
Economic development in emerging markets
The role of entrepreneurship in economic growth
Impact of social media on political engagement
Effects of social isolation on mental health
Cultural influences on parenting styles
Social consequences of income inequality
Social dynamics in online communities
Gender roles in contemporary society
Impact of technology on interpersonal relationships
Immigration and its effects on social integration
Social movements: Causes and outcomes
The psychology of resilience in the face of adversity
Cross-cultural perspectives on emotional intelligence
The impact of childhood experiences on adult relationships
The impact of social media on political polarization
Electoral systems and their influence on representation
International relations: Power dynamics and conflict resolution
Global governance: Challenges and opportunities
The role of diplomacy in international relations
The portrayal of gender roles in contemporary literature
The influence of folklore on modern storytelling
The evolution of language in the digital age
Analysis of post-colonial literature and its impact
The role of literature in fostering empathy
The impact of art therapy on mental health
Cultural influences on contemporary art
Analysis of symbolism in contemporary art movements
Existentialist perspectives on human freedom
Metaethics: Examining the nature of ethical statements
The philosophy of education: Different approaches

Media Studies

Fake News and its Impact on Public Perception
The Evolution of Journalism in the Digital Age
Media Representation of Minorities: Challenges and Solutions
The Role of Satire in Political Commentary
Influencer Marketing: Consumer Trust and Ethical Considerations
Podcasting as a Medium for Alternative Narratives
Media Literacy Education: Navigating Information in the Digital Era
Virtual Reality and Immersive Storytelling in Media
The Relationship Between Media Consumption and Political Beliefs
Media Censorship: Balancing Freedom of Speech and Social Responsibility

Sociology of Religion

Interfaith Dialogue and Social Harmony
Religion and Environmental Stewardship
The Role of Religion in Shaping Gender Norms
Religious Pluralism in Diverse Societies
Faith-Based Initiatives in Social Welfare
Religious Fundamentalism and Its Impact on Society
Sacred Spaces: Architecture and Symbolism in Religious Buildings
Spirituality and Mental Health: Exploring Connections
The Influence of Religion on Political Movements
Secularism in Modern Societies: Trends and Debates

Computer Science

Explainable Artificial Intelligence: Bridging the Gap between Technology and Understanding
Quantum Computing Algorithms: Potential Applications and Limitations
Cybersecurity Threats in Internet of Things (IoT) Devices
Natural Language Processing for Multilingual Information Retrieval
Machine Learning for Predictive Maintenance in Manufacturing
Blockchain Technology in Supply Chain Management
Human-Computer Interaction: Enhancing User Experience
Edge Computing: Distributing Processing Power for Efficiency
Ethical Considerations in Autonomous Systems and Robotics
Augmented Reality Applications in Education and Training

Public Policy

Immigration Policies and Social Integration
Universal Basic Income: Economic and Social Implications
Public Health Policies for Disease Prevention
Education Policies: Assessing Impact on Student Outcomes
Climate Change Policy: International Cooperation and Challenges
Criminal Justice Reforms and Recidivism Rates
Social Welfare Programs: Effectiveness and Challenges
Affordable Housing Policies and Urban Development
The Role of Government in Addressing Income Inequality
Policy Responses to Global Health Crises

Tips for Narrowing Down Research Topics

Define Specific Research Questions

Once a general topic is identified, students should narrow down their focus by defining specific research questions. This helps clarify the scope of the research and ensures a more targeted and manageable investigation.

Consider Feasibility and Resources

Practical considerations, such as available resources and feasibility, play a crucial role in topic selection. Students should assess whether they have access to the necessary data, tools, and support to carry out their research effectively.

Evaluate Available Literature

Conducting a literature review is an essential step in refining research topics. By reviewing existing literature, students can identify gaps in knowledge, refine their research questions, and build on the work of previous scholars.

Seek Guidance from Mentors and Instructors

Engaging with mentors and instructors can provide valuable insights and guidance. They can offer feedback on proposed topics, suggest relevant literature, and provide support throughout the research process.

In conclusion, choosing a research topic (from research topic examples for students) is a pivotal step in a student’s academic journey. By considering personal interests, aligning with academic goals, and exploring examples across different domains, students can unlock the potential for meaningful and impactful research.

The outlined tips for narrowing down research topics serve as practical guidance, ensuring that students embark on a research journey that is both enriching and rewarding.

As students embrace the challenge of research, they contribute not only to their academic growth but also to the broader body of knowledge that shapes our understanding of the world. So, let the exploration begin!

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500 Good Research Paper Topics

Bonus Material: Essential essay checklist

Writing a research paper for a class and not sure how to start?

One of the most important steps to creating a great paper is finding a good topic!

Here’s a hand-drafted list from a Princeton grad who has helped professors at Harvard and Yale edit their papers for publication and taught college writing at the University of Notre Dame and .

What’s more, we give you some foolproof formulas for creating your own paper topic to fit the requirements of your class.

Using these simple formulas, we’ve helped hundreds of students turn a B- paper topic into an A+ paper topic.

Keep reading for our list of 500 vetted research paper topics and our magic formulas for creating your own topic!

Of course, if you want help learning to write research papers tailored to your individual needs, check out our one-on-one writing coaching or academic writing workshop . Set up a free consultation to see how we can help you learn to write A+ papers!

Jump to paper topics in:

European & Mediterranean History

African history, asian history, history of the pre-columbian americas.

Latin American History

History of Science

Politics & public policy, education & education policy, political theory, science policy.

Health Sciences & Psychology

What is a research paper?

In order to write a good research paper, it’s important to know what it is!

In general, we can divide academic writing into three broad categories:

Analytical: analyze the tools an author uses to make their point
Research: delve deeply into a research topic and share your findings
Persuasive : argue a specific and nuanced position backed by evidence

What’s the difference between an analytical paper and a research paper? For an analytical paper, it’s okay to just use one or two sources (a book, poem, work of art, piece of music, etc.) and examine them in detail. For a research paper, however, the expectation is that you do, well . . . research .

The depth of research that you’re expected to do will depend on your age and the type of class you’re taking.

In elementary or middle school, a “research paper” might mean finding information from a few general books or encyclopedias in your school library.

In high school, your teachers might expect you to start using information from academic articles and more specific books. You might use encyclopedias and general works as a starting point, but you’ll be expected to go beyond them and do more work to synthesize information from different perspectives or different types of sources. You may also be expected to do “primary research,” where you study the source material yourself, instead of synthesizing what other people have written about the source material.

In college, you’ll be required to use academic journals and scholarly books, and your professors will now expect that you be more critical of these secondary sources, noticing the methodology and perspectives of whatever articles and books you’re using.

In more advanced college courses, you’ll be expected to do more exhaustive surveys of the existing literature on a topic. You’ll need to conduct primary research that makes an original contribution to the field—the kind that could be published in a journal article itself.

For a walkthrough of the 12 essential steps to writing a good paper, check out our step-by-step guide .

Working on a research paper? Grab our free checklist to make sure your essay has everything it needs to earn an A grade.

Get the essential essay checklist

What makes a good research paper topic?

One of the most important features of a research paper topic is that it has a clear, narrow focus.

For example, your teacher may assign you to write a research paper related to the US Revolutionary War. Does that mean that your topic should be “the US Revolutionary War”?

Definitely not! There’s no way to craft a good paper with in-depth research with such a broad topic. (Unless you’re in elementary or middle school, in which case it’s okay to have a more general topic for your research paper.)

Instead, you need to find a more specific topic within this broader one. There are endless ways that you can make this narrower! Some ideas generated from this one broader topic might be:

Causes of the US Revolutionary War
Changes in military strategy during the Revolutionary War
The experiences of Loyalists to England who remained in the American colonies during the Revolutionary War
How the Revolutionary War was pivotal for the career of Alexander Hamilton
The role of alliances with France during the US Revolutionary War
The experiences of people of color during the Revolutionary War
How George Washington’s previous military career paved the way for his leadership in the Revolutionary War
The main types of weaponry during the Revolutionary War
Changes in clothing and fashion over the courses of the Revolutionary War
How Valley Forge was a key moment in the Revolutionary War
How women contributed to the Revolutionary War
What happened in Amherst, Massachusetts during the Revolutionary War
Field medicine during the Revolutionary War
How the Battle of Saratoga was a turning point in the Revolutionary War
How different opinions about the Revolutionary War were reflected in poetry written during that time
Debates over abolition during the Revolutionary War
The importance of supply chains during the Revolutionary War
Reactions to the US Revolutionary war in Europe
How the US Revolutionary war impacted political theory in England and France
Similarities and differences between the US Revolutionary War and the French Revolution
Famous paintings inspired by the US Revolutionary War
Different ways that the US Revolutionary War has been depicted in modern contemporary culture
The appropriation of the “Boston Tea Party” by US politicians in the 2010s

This list could go on forever!

good research paper topics about the US Revolution

In fact, any of these topics could become even more specific. For example, check out the evolution of this topic:

Economic causes of the Revolutionary war
The way that tax policies helped lead to the Revolutionary War
How tax laws enacted 1763–1775 helped lead to the Revolutionary War
How the tax-free status of the British East India Company helped lead to the Revolutionary War
How the 1773 tax-free status of the British East India Company helped lead to the Revolutionary War, as reflected in letters written 1767–1775
How the 1773 tax-free status of the British East India Company helped lead to the Revolutionary War, as reflected in letters written by members of the Sons of Liberty 1767–1775

As you advance in your educational career, you’ll need to make your topic more and more specific. Steps 1–3 of this topic might be okay in high school, but for a college research paper steps 4–7 would be more appropriate!

As you craft your research paper topic, you should also keep in mind the availability of research materials on your subject. There are millions of topics that would make interesting research papers, but for which you yourself might not be able to investigate with the primary and secondary sources to which you have access.

Access to research materials might look like:

To the best of our knowledge, the sources exist somewhere
The source isn’t behind a paywall (or you or your school can pay for it)
Your school or local library has a copy of the source
Your school or local library can order a copy of the source for you
The source is in a language that you speak
The source has been published already (there’s tons of amazing research that hasn’t been published yet, a frustrating problem!)
You can access the archive, museum, or database where the primary source is held—this might mean online access or travel! To access a source in an archive or museum you’ll often need permission, which often requires a letter of support from your school.

If you’re not sure about access to source materials, talk to a librarian! They’re professionals for this question.

Finally, pick a research topic that interests you! Given that there are unlimited research topics in the world and many ways to adapt a broad topic, there should absolutely be a way to modify a research topic to fit your interests.

Want help learning to write an amazing research paper? Work one-on-one with an experienced Ivy-League tutor to improve your writing skills or sign up for our bestselling academic writing workshop .

Insider tips to generate your own research paper topic

Use these formulas to generate your own research paper topics:

How did X change over a period of time (year, decade, century)?
What is the impact (or consequences) of X?
What led to X?
What is the role of X in Y?
How did X influence Y?
How did X become Y?
How was X different from Y?
How is X an example of Y?
How did X affect Y?
What were some reactions to X?
What are the most effective policies to produce X result?
What are some risks of X?
How is our current understanding of X incorrect? (advanced)
What happens if we look at X through the lens of Y theory or perspective? (advanced)

A good research paper topic often starts with the question words—why, how, what, who, and where. Remember to make it as specific as possible!

Good research paper topics

These research paper topics have been vetted by a Princeton grad and academic book editor!

How did European rivalries (British vs French) impact North American history?
What was the role of British and French alliances with indigneous tribes during the Seven Years’ War?
Reactions to the 1754 Albany Congress among North American intellectual figures
How the Albany Plan served as a model for future attempts at union among the North American colonies
How did different religious identities (Calvinist, Catholic, etc.) play a role in the aftermath of the Seven Years’ War?
What were the consequences of the 1763 Treaty of Paris?
How did the Seven Years’ War impact British debt and colonial economics?
What were some causes of the US Revolutionary War?
How did military strategy change during the Revolutionary War?
What were the experiences of Loyalists to England who remained in the American colonies during the Revolutionary War?
How was the Revolutionary War pivotal for the career of Alexander Hamilton?
What was the role of alliances with France during the US Revolutionary War?
What were the experiences of people of color during the Revolutionary War?
How did George Washington’s previous military career pave the way for his leadership in the Revolutionary War?
What were the main types of weaponry during the Revolutionary War? How did that affect the options for military strategies?
How did clothing and fashion change over the courses of the Revolutionary War?
How was Valley Forge a key moment in the Revolutionary War?
How did women contribute to the Revolutionary War?
What happened in Amherst, Massachusetts (or any other specific location) during the Revolutionary War?
What was field medicine like during the Revolutionary War?
How was the Battle of Saratoga a turning point in the Revolutionary War?
How were different opinions about the Revolutionary War reflected in poetry written during that time?
What were the debates over abolition during the Revolutionary War?
What was the role of supply chains during the Revolutionary War?
What were reactions to the US Revolutionary war like in Europe? What does that tell us about politics in England, France, the Netherlands, etc?
How did the US Revolutionary war impact political theory in England and France?
What are similarities and differences between the US Revolutionary War and the French Revolution?
What are some famous paintings inspired by the US Revolutionary War? What do differences between these paintings tell us about how the artists who created them saw the war?
What are some different ways that the US Revolutionary War has been depicted in modern contemporary culture? What does that tell us?
How was the story of the “Boston Tea Party” appropriated by US politicians in the 2010s, and why?
What was the difference between the Federalists and the Jeffersonians?
How did the 1797 XYZ Affair lead to the Quasi-War with France?
How were loans from European countries and companies (France, Spain, Dutch bankers) key to the early US?
What were reactions to the Constitutional Convention of 1787?
Why did the US remain neutral during the French Revolution?
How did the Alien and Sedition acts contribute to the election of Thomas Jefferson as president?
What was the US’s reaction to the Haitian revolution? Why did the US not recognize Haitian independence until 1862?
What were the reactions to John Jay’s Treaty of 1794?
How have the remarks made by George Washington in his Farewell Address inspired isolationist policies?
How did interpretations of the Monroe Doctrine change over the decades since its creation?
How did the Roosevelt Corollary and Lodge Corollary change and expand the Monroe Doctrine?
How did the presence of US companies like the United Fruit Company affect US military interventions in Latin America?
How was the Monroe Doctrine invoked in the Cuban Missile Crisis of 1962?
How was US culture shaped by the Cold War?
How did ecology play a role in the rise of Ancient Egypt?
How did water management technologies impact Ancient Egypt?
How did bureaucracies function in Ancient Egypt?
How did Egyptian art influence Ancient Greek art?
Who could be a citizen in Athens in the 5th century BCE? What does this tell us about classical Athenian society?
What was the impact of the Peloponnesian War?
What was the impact of Alexander the Great’s attempt to create an empire?
How does the way that Alexander the Great is represented in art demonstrate conceptions about the relationship between the human and the divine?
Was there a conception of race in the ancient world? How were these ideas different from our own modern conceptions of race?
What was the role of debt slavery in the Roman republic? How were these policies ended, and what is the significance of the end of debt slavery? What kinds of slavery remained?
To what degree does the movie Gladiator accurately the Roman Empire in 176–192 CE?
What was the role of slavery in managing the large latifundia ?
How and why did the emperor Constantine I adopt Christianity?
How did patterns of urbanism in the latter Roman empire change? What does this tell us about challenges being faced at that time?
What do reactions to the Byzantine empress Theodora tell us about ideas of gender in 6th-century Byzantium?
How did scientific advancements in Islamic Spain influence the rest of Europe?
What was the relationship between Muslim, Christian, and Jewish populations in Islamic Spain? How does this compare to the experience of Muslim and Jewish populations in Christian Spain?
How did medieval troubadour poetry represent a new idea of romantic relationships?
What are similarities and differences between medieval troubadour poetry and lyric poetry in Ancient Greece?
What do letters between women and popes tell us about gender, power, and religion in medieval Europe?
In what ways was Hildegard of Bingen groundbreaking for her time?
Who produced beer in medieval England, and what does this tell us about society?
How did the adoption of hops affect the production and distribution of beer?
How did beer production allow some women a way to be financially independent?
How was clothing used to mark religious and cultural identities in 15th- and 16th-century Spain?
How did print culture change relationships and courting in Georgian England?
How did churches function as social gathering spaces in Georgian England?
To what degree is Netflix’s Bridgerton series historically accurate?
How did ideas of love change in the 18th century? How did philosophy play a role in this?
When were Valentine cards first commercially available? What does that show us about cultural ideas of love and courtship?
What were the consequences of the desertification of the Sahara?
How did trade links on the Red Sea influence Nubian culture?
How did Carthage build power in Northern Africa around 600–500 BCE?
What was the impact of the Mercenary War (241–238 BCE) in Carthage?
How did the Roman province of Africa play a key role in financing the Roman Empire?
What were the consequences of the Donatist division in the 300s in Northern Africa?
What was the impact of the large-scale movement of Bedouins from the Arabian peninsula into the Maghreb?
How was Mande society organized in the Mali Empire?
What was the role of the book trade in Timbuktu? What does this tell us about culture and learning in the Mali Empire?
How did Aksum use trade to build wealth and power?
What do Nok terracotta sculptures tell us about Nok culture?
How did the Luba Empire create a centralized political system? How did the idea of spiritual kins ( balopwe ) play a role in this system?
How did tax collection work in the Lunda empire?
What does it mean to say that the Ajuran Empire was a hydraulic empire? How did control over water resources allow the Ajuran Empire to build and consolidate power?
What is the significance of diplomatic ties between the Somai Ajuran Empire and Ming dynasty China?
How did the tribute system in the Kingdom of Kongo help to stimulate interregional trade?
What was the impact of the introduction of maize and cassava to the Kingdom of Kongo?
How did women wield influence in the Kingdom of Benin?
How did the Industrial Revolution in Europe help lead to the Scramble for Africa 1878–1898?
What were the consequences of the Second Boer War?
What happened in the Year of Africa (1960)?
How did the Han dynasty consolidate power in frontier regions?
How and why did the Han dynasty nationalize the private salt and iron industries in 117 BCE?
What are the earliest records of papermaking, and what is the significance of this invention?
What was the role of Daoist religious societies in rebellions at the end of the Han dynasty (Yellow Turban Rebellion, Five Pecks of Rice Rebellion)?
What do tomb paintings tell us about ancient Chinese society?
What was the impact of the Sui dynasty’s standardization and re-unification of the coinage?
What was the role of standardized testing in Sui dynasty and Tang dynasty China?
Why is the Tang dynasty often regarded as a golden age of cosmopolitan culture in Chinese history?
What was the role of slavery in imperial China?
How did the rise of jiedushi (regional military governments) undermine the civil-service system? What were the consequences of this?
How did Tang dynasty China exert power over Japan and Korea?
What was the Three Departments and Six Ministries system in imperial China and how did it work?
What does the appearance of Inca, Maya, and Aztec goods in North America (Utah, Canada) and the appearance of goods from the Great Lakes region in Maya and Aztec ruins tell us about trade in the Pre-Columbian Americas?
How did celebration of maize play a central role in Mesoamerican cultures?
How did the Aztec empire use relationships with client city-states to establish power? How did the Aztec empire use taxation to exert power?
How did the luxury good trade impact Aztec political power?
How did the building of roads play a key role in the Aztec empire?
How and why has archaeology played a pivotal role in expanding our understanding of the pre-Columbian Americas?
What are some common misconceptions about the Americas in the year 1491? Why do these misconceptions exist?

Latin American History (post-1492)

How and why did the Spanish appropriate Aztec sites of significance (e.g. Mexico City at the site of Tenochtitlan)?
What were reactions among Latin American intellectuals (e.g. Luis María Drago, Alejandro Álvarez and Baltasar Brum) to the Monroe Doctrine?
How was the US’s involvement in the Venezuela Crisis of 1902–1903 a pivotal turning point in the relationship between the US and Latin American countries?
What were the effects of the US’s involvement in the Cuban War for Independence?
How did the Roosevelt Corollary of 1904 benefit the US?
How did Simon Bolivar’s time in Europe affect his ideas about Latin American independence?
How did 19th century academic societies play a role in the advancement of scientific discoveries? Who was excluded from these societies?
How was music connected to the sciences in medieval thinking?
When was the concept of zero first used, and how was it instrumental for advancements in math?
What role did Islamic Spain play in the spread of scientific advancements in medieval Europe?
What role has translation between languages played in the development of sciences?
Why were Galileo’s ideas about astronomy controversial at the time?
What was the connection between art and advancements in human anatomy?
Why were Darwin’s ideas about natural selection controversial at the time?
To what degree does the film Master and Commander accurately depict the voyages of Charles Darwin?
How did the discovery of quinine and other medical innovations help to facilitate the European colonization of Africa?
How and why was the internet invented?
Does Virgil’s Aeneid celebrate the new Roman Empire or subvert it?
Why was the poet Ovid exiled from Rome?
What are the pagan influences in Beowulf ? What are the Christian elements in Beowulf ? What does that tell us about late Anglo-Saxon England?
How does Chaucer’s Canterbury Tales reflect gender roles in late medieval England?
How does Dante’s Inferno draw on book IV of Virgil’s Aeneid ?
How are gender roles presented and subverted in Shakespeare’s plays?
To what degree did Henry David Thoreau live out the ideals he described in Walden in his own life?
How did the serialized publication of novels affect the way that they were written?
Does Dickens’ novel A Tale of Two Cities accurately portray the French Revolution?
How did 18th-century novels propagate the idea of marrying for love?
What did contemporary readers think about Jane Austen and her novels?
To what degree do Jane Austen’s novels reflect economic realities for women in Regency England? What do they leave out?
How did Lord Byron’s personal life affect his poetry?
What do we know about the romantic life of Emily Dickinson?
What were the religious movements that influenced the writer George Eliot, and how do those influences appear in her novels?
In what ways were Walt Whitman’s writings new or different?
How did British poets react to the horrors of Word War I?
What do Tolkien’s letters reveal about the ways in which the two world wars influenced his writings?
How did the friendship between CS Lewis and Tolkien affect their respective writings?
What are the arguments for and against Catalonian independence from Spain?
What are the arguments for and against Scottish independence from the United Kingdom?
What are some risks of contact sports, especially for children?
What are the most effective policies for combating childhood obesity?
What are the most effective policies for reducing gun violence?
Which countries have the longest life expectancy and why?
What are some differences between the healthcare system in the US and in European countries? Which country has the most similar system to the US?
What policies for parental leave exist in different countries? What are some effects of these policies?
Has the drinking age in the US always been 21? What have been some different policies, and what were some consequences of them?
What is the debate around museum artifacts like the Elgin Marbles in London or the Benin Bronzes in Berlin?
How have politicians attempted to control population growth in different countries, either directly or indirectly? What have been some effects of these policies?
Which countries have the most gender parity reflected in national governments? How have they accomplished this?
How has public funding of K-12 education changed since the 1930s in the US?
How has public funding of higher education changed in the US?
What is early childhood education like in different countries?
What are some effects of free or reduced-cost meals in schools?
How does access to menstrual products affect education outcomes for girls in different countries?
What was the impact of Rousseau’s writings on education?
How did Plato’s ideal forms of government reflect contemporary Athenian concerns about the unruly masses ( demos )?
How did Aristotle justify slavery?
How has wealth inequality increased in recent decades?
How is inflation calculated, and what are the implications of this methodology?
How have genetically-engineered crops changed the way that the planet feeds itself?
How has animal testing changed since 2000?
How is animal testing regulated differently in different countries?

Health Sciences and Psychology

How do different societies reflect the natural circadian rhythms of the human body?
How does secondhand smoke affect the human body?
How does lack of sleep affect the body?
How does stress affect the body?
What are some ways to reduce stress?
How have cancer treatments changed in the past 30 years?
Why is it hard to find a “cure” for cancer?
How has the Human Genome Project changed medical science?
How were the Covid vaccines developed so quickly? What is the difference between the various Covid vaccines that have been developed?

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Research Paper Topics

Choose your Topic Smart

What starts well, ends well, so you need to be really careful with research paper topics. The topic of a research paper defines the whole piece of writing. How often have you chosen the book by its title? First impression is often influential, so make sure your topic will attract the reader instantly. By choosing your topic smart, the half of your job is done. That is why we have singled out several secrets on how to pick the best topic for you. Also see the list of 1000 thesis topics .

Browse Research Paper Topics by Category:

Anthropology
Argumentative
Communication
Criminal Justice
Environmental
Political Science

What is the Key to a Perfect Topic for a Research Paper?

The key to a perfect topic includes three main secrets: interest, precision, and innovation.

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It is impossible to do something great if you have no interest in what you are doing. For this reason, make sure you choose the topic that drives you. If you are bored by what you investigate, do not expect that your paper will be exciting. Right now, spend some minutes or even hours thinking about what interests you. Jot down all your preferences in life, science, politics, social issues etc. It will help you get the idea what you can write about.

After realizing what drives you, narrow this general idea to a more specific one. A research paper is not about beating around the bush. You will need clear facts and data. You will have to provide evidence to your ideas. You will need to be precise, specific and convincing.

Finally, the idea of any research is that it should be surprising and distinctive. Think what makes your perspective and approach special. What is the novelty of your research?

Use Technology

If you are still stuck, use technology. Today we have an opportunity to make our lives easier with a bit of technology used. You can find paper topic generators online. This software will examine the category you want to investigate and the keywords from your research. Within several seconds, this program generates paper topics, so you can try it yourself. It can help you get started with your assignment.

100% Effective Advice

We will now give you advice that is 100% effective when picking the topic. Firstly, forget about what others may think about your topic. This is your topic and this is your perception of the world. Stay personal and let your personal style get you the top grades. Secondly, never decide on the topic before analyzing the background for your research. By this we mean, investigate the topic before you start the research proper. It happens quite often that students choose the topic and later they realize there is no data or information to use. That is why conduct some research beforehand. Thirdly, read other researchers’ papers on the topic you want to write about. It will help you get the idea of the investigation. Moreover, it will help you understand whether you truly want to write a paper on this topic. Finally, when you have picked the topic, started your research, make sure you dedicate your time and energy. If you want to get high results, you need to study every little details of your research.

Examine Different Ideas

People often come up with genius ideas after analyzing thousands of other people’s ideas. This is how our brain works. That is why you can analyze other people’s ideas for research paper topics and think up your own. If you have never written any paper of that kind, it will help you understand the gist of this assignment, the style and the requirements. By comparing different topics, you can motivate yourself and get inspired with these ideas. Luckily, you have come to the right place. Here is our list of top 100 research paper topics.

What Makes a Good Topic for a Research Paper?

A good research paper topic is the one that is successful and manageable in your particular case. A successful research paper poses an interesting question you can actually answer. Just as important, it poses a question you can answer within the time available. The question should be one that interests you and deserves exploration. It might be an empirical question or a theoretical puzzle. In some fields, it might be a practical problem or policy issue. Whatever the question is, you need to mark off its boundaries clearly and intelligently so you can complete the research paper and not get lost in the woods. That means your topic should be manageable as well as interesting and important.

A topic is manageable if you can:

Master the relevant literature
Collect and analyze the necessary data
Answer the key questions you have posed
Do it all within the time available, with the skills you have

A topic is important if it:

Touches directly on major theoretical issues and debates, or
Addresses substantive topics of great interest in your field

Ideally, your topic can do both, engaging theoretical and substantive issues. In elementary education, for example, parents, teachers, scholars, and public officials all debate the effectiveness of charter schools, the impact of vouchers, and the value of different reading programs. A research paper on any of these would resonate within the university and well beyond it. Still, as you approach such topics, you need to limit the scope of your investigation so you can finish your research and writing on time. After all, to be a good research paper, it first has to be a completed one. A successful research paper poses an interesting question you can actually answer within the time available for the project. Some problems are simply too grand, too sweeping to master within the time limits. Some are too minor to interest you or anybody else.

The solution, however, is not to find a lukewarm bowl of porridge, a bland compromise. Nor is it to abandon your interest in larger, more profound issues such as the relationship between school organization and educational achievement or between immigration and poverty. Rather, the solution is to select a well-defined topic that is closely linked to some larger issue and then explore that link. Your research paper will succeed if you nail a well-defined topic. It will rise to excellence if you probe that topic deeply and show how it illuminates wider issues.The best theses deal with important issues, framed in manageable ways. The goal is to select a well-defined topic that is closely linked to some larger issue and can illuminate it.

You can begin your project with either a large issue or a narrowly defined topic, depending on your interests and the ideas you have generated. Whichever way you start, the goals are the same: to connect the two in meaningful ways and to explore your specific topic in depth.

Of course, the choice of a particular research paper topic depends on the course you’re taking. Our site can offer you the following research paper topics and example research papers:

Moving from a Research Paper Idea to a Research Paper Topic

Let’s begin as most students actually do, by going from a “big issue” to a more manageable research paper topic. Suppose you start with a big question such as, “Why has the United States fought so many wars since 1945?” That’s certainly a big, important question. Unfortunately, it’s too complex and sprawling to cover well in a research paper. Working with your professor or instructor, you could zero in on a related but feasible research topic, such as “Why did the Johnson administration choose to escalate the U.S. war in Vietnam?” By choosing this topic, your research paper can focus on a specific war and, within that, on a few crucial years in the mid-1960s.

You can draw on major works covering all aspects of the Vietnam War and the Johnson administration’s decision making. You have access to policy memos that were once stamped top secret. These primary documents have now been declassified, published by the State Department, and made available to research libraries. Many are readily available on the Web. You can also take advantage of top-quality secondary sources (that is, books and articles based on primary documents, interviews, and other research data).

Drawing on these primary and secondary sources, you can uncover and critique the reasons behind U.S. military escalation. As you answer this well-defined question about Vietnam, you can (and you should) return to the larger themes that interest you, namely, “What does the escalation in Southeast Asia tell us about the global projection of U.S. military power since 1945?” As one of America’s largest military engagements since World War II, the war in Vietnam should tell us a great deal about the more general question.

The goal here is to pick a good case to study, one that is compelling in its own right and speaks to the larger issue. It need not be a typical example, but it does need to illuminate the larger question. Some cases are better than others precisely because they illuminate larger issues. That’s why choosing the best cases makes such a difference in your research paper.

Since you are interested in why the United States has fought so often since 1945, you probably shouldn’t focus on U.S. invasions of Grenada, Haiti, or Panama in the past two decades. Why? Because the United States has launched numerous military actions against small, weak states in the Caribbean for more than a century. That is important in its own right, but it doesn’t say much about what has changed so dramatically since 1945. The real change since 1945 is the projection of U.S. power far beyond the Western Hemisphere, to Europe and Asia. You cannot explain this change—or any change, for that matter—by looking at something that remains constant.

In this case, to analyze the larger pattern of U.S. war fighting and the shift it represents, you need to pick examples of distant conflicts, such as Korea, Vietnam, Kosovo, Afghanistan, or Iraq. That’s the noteworthy change since 1945: U.S. military intervention outside the Western Hemisphere. The United States has fought frequently in such areas since World War II but rarely before then. Alternatively, you could use statistics covering many cases of U.S. intervention around the world, perhaps supplemented with some telling cases studies.

Students in the humanities want to explore their own big ideas, and they, too, need to focus their research. In English literature, their big issue might be “masculinity” or, to narrow the range a bit, “masculinity in Jewish American literature.” Important as these issues are, they are too vast for anyone to read all the major novels plus all the relevant criticism and then frame a comprehensive research paper.

If you don’t narrow these sprawling topics and focus your work, you can only skim the surface. Skimming the surface is not what you want to do in a research paper. You want to understand your subject in depth and convey that understanding to your readers.

That does not mean you have to abandon your interest in major themes. It means you have to restrict their scope in sensible ways. To do that, you need to think about which aspects of masculinity really interest you and then find works that deal with them.

You may realize your central concern is how masculinity is defined in response to strong women. That focus would still leave you considerable flexibility, depending on your academic background and what you love to read. That might be anything from a reconsideration of Macbeth to an analysis of early twentieth-century American novels, where men must cope with women in assertive new roles. Perhaps you are interested in another aspect of masculinity: the different ways it is defined within the same culture at the same moment. That would lead you to novelists who explore these differences in their characters, perhaps contrasting men who come from different backgrounds, work in different jobs, or simply differ emotionally. Again, you would have considerable flexibility in choosing specific writers.

Connecting a Specific Research Paper Topic to a Bigger Idea

Not all students begin their research paper concerned with big issues such as masculinity or American wars over the past half century. Some start with very specific topics in mind. One example might be the decision to create NAFTA, the North American Free Trade Agreement encompassing Canada, the United States, and Mexico. Perhaps you are interested in NAFTA because you discussed it in a course, heard about it in a political campaign, or saw its effects firsthand on local workers, companies, and consumers. It intrigues you, and you would like to study it in a research paper. The challenge is to go from this clear-cut subject to a larger theme that will frame your paper.

Why do you even need to figure out a larger theme? Because NAFTA bears on several major topics, and you cannot explore all of them. Your challenge—and your opportunity—is to figure out which one captures your imagination.

One way to think about that is to finish this sentence: “For me, NAFTA is a case of ___________.” If you are mainly interested in negotiations between big and small countries, then your answer is, “For me, NAFTA is a case of a large country like the United States bargaining with a smaller neighbor.” Your answer would be different if you are mainly interested in decision making within the United States, Mexico, or Canada. In that case, you might say, “NAFTA seems to be a case where a strong U.S. president pushed a trade policy through Congress.” Perhaps you are more concerned with the role played by business lobbies. “For me, NAFTA is a case of undue corporate influence over foreign economic policy.” Or you could be interested in the role of trade unions, environmental groups, or public opinion.

The NAFTA decision is related to all these big issues and more. You cannot cover them all. There is not enough time, and even if there were, the resulting paper would be too diffuse, too scattershot. To make an impact, throw a rock, not a handful of pebbles.

Choosing one of these large issues will shape your research paper on NAFTA. If you are interested in U.S. decision making, for example, you might study the lobbying process or perhaps the differences between Democrats and Republicans. If you are interested in diplomacy, you would focus on negotiations between the United States, Canada, and Mexico. Either would make an interesting research paper, but they are different topics.

Although the subject matter and analysis are decidedly different in the humanities, many of the same considerations still apply to topic selection. In English or comparative literature, for example, you may be attracted to a very specific topic such as several poems by William Wordsworth. You are not trying, as a social scientist would, to test some generalizations that apply across time or space. Rather, you want to analyze these specific poems, uncover their multiple meanings, trace their allusions, and understand their form and beauty.

As part of the research paper, however, you may wish to say something bigger, something that goes beyond these particular poems. That might be about Wordsworth’s larger body of work. Are these poems representative or unusual? Do they break with his previous work or anticipate work yet to come? You may wish to comment on Wordsworth’s close ties to his fellow “Lake Poets,” Coleridge and Southey, underscoring some similarities in their work. Do they use language in shared ways? Do they use similar metaphors or explore similar themes? You may even wish to show how these particular poems are properly understood as part of the wider Romantic movement in literature and the arts. Any of these would connect the specific poems to larger themes.

How to Refine Your Research Paper Topic

One of your professor’s or instructor’s most valuable contributions to the success of your research paper is to help you refine your topic. She can help you select the best cases for detailed study or the best data and statistical techniques. S/he can help you find cases that shed light on larger questions, have good data available, and are discussed in a rich secondary literature. She may know valuable troves of documents to explore. That’s why it is so important to bring these issues up in early meetings. These discussions with your instructor are crucial in moving from a big but ill-defined idea to a smart, feasible topic.Some colleges supplement this advising process by offering special workshops and tutorial support for students. These are great resources, and you should take full advantage of them. They can improve your project in at least two ways.

First, tutors and workshop leaders are usually quite adept at helping you focus and shape your topic. That’s what they do best. Even if they are relatively new teachers, they have been writing research papers themselves for many years. They know how to do it well and how to avoid common mistakes. To craft their own papers, they have learned how to narrow their topics, gather data, interpret sources, and evaluate conjectures. They know how to use appropriate methods and how to mine the academic literature. In all these ways, they can assist you with their own hard-won experience. To avoid any confusion, just make sure your instructor knows what advice you are getting from workshop leaders and tutors. You want everyone to be pulling in the same direction.

Second, you will benefit enormously from batting around your research paper in workshops. The more you speak about your subject, the better you will understand it yourself. The better you understand it, the clearer your research and writing will be. You will learn about your project as you present your ideas; you will learn more as you listen to others discuss your work; and you will learn still more as you respond to their suggestions. Although you should do that in sessions with your instructor, you will also profit from doing it in workshops and tutorial sessions.

Secrets to Keep in Mind when Writing a Research Paper

As a bonus, we have prepared several secrets for you to make your paper perfect. Firstly, always write your paper from scratch. Do not copy the already existing materials, as it can lead to unsatisfactory mark or even expulsion. Secondly, start your research early; do not put off investigating the topic. The earlier you start, the easier it will be to meet the deadline. Thirdly, plan your work and create an outline for your task. A planned work will help you be systematic. Plus, it will help you avoid writer’s block, as you always have an outline to follow. Another secret is following all the requirements. A research paper is an academic assignment, so all these structural and formatting standards are important. Finally, make sure you proofread and edit your task. Check your paper for grammar and spelling mistakes, examine your choice of vocabulary. If it seems too much, you can always ask our professional editors and they will check the paper for you. A mistakes-free paper is essential to get high results.

Custom Research Paper Writing Service

If you still have concerns regarding your research paper, we are here to answer your questions. It is no secret that studying is becoming more and more difficult at college. Every week you have an overload of tasks and assignments. You work hard, sleep little. As a result, you can be at the edge of a nervous breakdown trying to finish all the tasks on time. That is why we are here helping thousands of students to study smart.

24/7 you can contact us and order your paper. We never miss the deadline and always provide our clients with a top-notch quality. When you feel that you cannot handle it on your own, a bit of assistance will do no harm. All our writers are experts with years of experience. They are aware of all the subtleties of academic writing and they know all the recent college requirements. You can turn to us for help any time and we will get down to work immediately. From choosing the topic to writing the whole paper – this is what we have to offer. Getting top grades is much easier when the real professionals help you.

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SCC Research Guides
Choosing a Research Topic
What Makes a Good Research Topic?

Before diving into how to choose a research topic, it is important to think about what are some elements of a good research topic. Of course, this will depend specifically on your research project, but a good research topic will always:

Relate to the assignment itself. Even when you have a choice for your research topic, you still want to make sure your chosen topic lines up with your class assignment sheet.
A topic that is too broad will give you too many sources, and it will be hard to focus your research.
A topic that is too narrow will not give you enough sources, if you can find any sources at all.
Is debatable. This is important if you are researching a topic that you will have to argue a position for. Good topics have more than one side to the issue and cannot be resolved with a simple yes or no.
Should be interesting to you! It's more fun to do research on a topic that you are interested in as opposed to one you are not interested in.

Remember, it is common and normal if your research topic changes as you start brainstorming and doing some background research on your topic.

Start with a General Idea

As an example, let's say you were writing a paper about issues relating to college students

<< Previous: Choosing a Research Topic
Next: 1. Concept Mapping >>
1. Concept Mapping
2. Background Research
3. Narrow Your Topic / Thesis Statements

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Last Updated: Jul 19, 2024 1:21 PM
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Boston University Libraries

Choosing a Research Topic

Starting Points

Where to Find Ideas

Persuasive paper assignments, dissertations and theses.

From Idea to Search
Make It Manageable

If you are starting a research project and would like some help choosing the best topic, this guide is for you. Start by asking yourself these questions:

What does your instructor require? What interests you? What information sources can support your research? What is doable in the time you have?

While keeping these questions in mind, find suggestions in this guide to select a topic, turn that topic into a database search, and make your research manageable. You will also find more information in our About the Research Process guide.

Whether your instructor has given a range of possible topics to you or you have to come up with a topic on your own, you could benefit from these activities:

Consult Course Materials If a reading, film, or other resource is selected by your instructor, the subject of it is important to the course. You can often find inspiration for a paper in these materials.

Is a broad topic presented? You can focus on a specific aspect of that topic. For example, if your class viewed a film on poverty in the United States, you could look at poverty in a specific city or explore how poverty affects Americans of a specific gender, ethnic group, or age range.
Are experts presented, quoted, or cited? Look up their work in BU Libraries Search or Google Scholar .

Use Background Sources If you've identified one or more topics you'd like to investigate further, look them up in an encyclopedia, handbook, or other background information source. Here are some good places to start.

Online version of Encyclopædia Britannica along Merriam-Webster’s Collegiate Dictionary and Thesaurus, magazines and periodicals and other reference sources.

Oxford Reference This link opens in a new window Published by Oxford University Press, it is a fully-indexed, cross-searchable database containing dictionaries, language reference and subject reference works.

Explore the Scholarly Literature Ask your instructor or a librarian to guide you to the top journals in the field you're studying. Scanning the tables of contents within these journals will provide some inspiration for your research project. As a bonus, each of the articles in these journals will have a bibliography that will lead you to related articles, books, and other materials.

Ask a Librarian We are here to help you! You can request a consultation or contact us by email or through our chat service . We can help you identify what interests you, where to find more about it, and how to narrow the topic to something manageable in the time you have.

If your assignment entails persuading a reader to adopt a position, you can conduct your research in the same way you would with any other research project. The biggest mistake you can make, however, is choosing a position before you start your research. Instead, the information you consult should inform your position. Researching before choosing a position is also much easier; you will be able to explore all sides of a topic rather than limiting yourself to one.

If you would like examples of debates on controversial topics, try these resources:

Covers the most current and controversial issues of the day with summaries, pros and cons, bibliographies and more. Provides reporting and analysis on issues in the news, including issues relating to health, social trends, criminal justice, international affairs, education, the environment, technology, and the economy.

New York Times: Room for Debate Selections from the New York Times' opinion pages.
ProCon.org Created by Britannica, this site exposes readers to two sides of timely arguments. Each article includes a bibliography of suggested resources.

If you are writing a dissertation or thesis, you will find more specialized information at our Guide for Writers of Theses and Dissertations .

If you would like to find published dissertations and theses, please use this database:

This database contains indexing and abstracts of American doctoral dissertations accepted at accredited institutions since 1861 and a selection from other countries. Masters level theses are included selectively.

Next: From Idea to Search >>
Last Updated: Aug 2, 2024 12:06 PM
URL: https://library.bu.edu/choosing-a-topic

Home » Research Topics – Ideas and Examples

Research Topics – Ideas and Examples

Table of Contents

Research Topic

Definition:

Research topic is a specific subject or area of interest that a researcher wants to investigate or explore in-depth through research. It is the overarching theme or question that guides a research project and helps to focus the research activities towards a clear objective.

How to Choose Research Topic

You can Choose a Research Topic by following the below guide:

Identify your Interests

One of the most important factors to consider when choosing a research topic is your personal interest. This is because you will be spending a considerable amount of time researching and writing about the topic, so it’s essential that you are genuinely interested and passionate about it. Start by brainstorming a list of potential research topics based on your interests, hobbies, or areas of expertise. You can also consider the courses that you’ve enjoyed the most or the topics that have stood out to you in your readings.

Review the Literature

Before deciding on a research topic, you need to understand what has already been written about it. Conducting a preliminary review of the existing literature in your field can help you identify gaps in knowledge, inconsistencies in findings, or unanswered questions that you can explore further. You can do this by reading academic articles, books, and other relevant sources in your field. Make notes of the themes or topics that emerge and use this information to guide your research question.

Consult with your Advisor

Your academic advisor or a mentor in your field can provide you with valuable insights and guidance on choosing a research topic. They can help you identify areas of interest, suggest potential research questions, and provide feedback on the feasibility of your research proposal. They can also direct you towards relevant literature and resources that can help you develop your research further.

Consider the Scope and Feasibility

The research topic you choose should be manageable within the time and resource constraints of your project. Be mindful of the scope of your research and ensure that you are not trying to tackle a topic that is too broad or too narrow. If your topic is too broad, you may find it challenging to conduct a comprehensive analysis, while if it’s too narrow, you may struggle to find enough material to support your research.

Brainstorm with Peers

Discussing potential research topics with your peers or colleagues can help you generate new ideas and perspectives. They may have insights or expertise that you haven’t considered, and their feedback can help you refine your research question. You can also join academic groups or attend conferences in your field to network with other researchers and get inspiration for your research.

Consider the Relevance

Choose a research topic that is relevant to your field of study and has the potential to contribute to the existing knowledge. You can consider the latest trends and emerging issues in your field to identify topics that are both relevant and interesting. Conducting research on a topic that is timely and relevant can also increase the likelihood of getting published or presenting your research at conferences.

Keep an Open Mind

While it’s essential to choose a research topic that aligns with your interests and expertise, you should also be open to exploring new ideas or topics that may be outside of your comfort zone. Consider researching a topic that challenges your assumptions or introduces new perspectives that you haven’t considered before. You may discover new insights or perspectives that can enrich your research and contribute to your growth as a researcher.

Components of Research Topic

A research topic typically consists of several components that help to define and clarify the subject matter of the research project. These components include:

Research problem or question: This is the central issue or inquiry that the research seeks to address. It should be well-defined and focused, with clear boundaries that limit the scope of the research.
Background and context: This component provides the necessary background information and context for the research topic. It explains why the research problem or question is important, relevant, and timely. It may also include a literature review that summarizes the existing research on the topic.
Objectives or goals : This component outlines the specific objectives or goals that the research seeks to achieve. It should be clear and concise, and should align with the research problem or question.
Methodology : This component describes the research methods and techniques that will be used to collect and analyze data. It should be detailed enough to provide a clear understanding of how the research will be conducted, including the sampling method, data collection tools, and statistical analyses.
Significance or contribution : This component explains the significance or contribution of the research topic. It should demonstrate how the research will add to the existing knowledge in the field, and how it will benefit practitioners, policymakers, or society at large.
Limitations: This component outlines the limitations of the research, including any potential biases, assumptions, or constraints. It should be transparent and honest about the potential shortcomings of the research, and how these limitations will be addressed.
Expected outcomes or findings : This component provides an overview of the expected outcomes or findings of the research project. It should be realistic and based on the research objectives and methodology.

Purpose of Research Topic

The purpose of a research topic is to identify a specific area of inquiry that the researcher wants to explore and investigate. A research topic is typically a broad area of interest that requires further exploration and refinement through the research process. It provides a clear focus and direction for the research project, and helps to define the research questions and objectives. A well-defined research topic also helps to ensure that the research is relevant and useful, and can contribute to the existing body of knowledge in the field. Ultimately, the purpose of a research topic is to generate new insights, knowledge, and understanding about a particular phenomenon, issue, or problem.

Characteristics of Research Topic

some common characteristics of a well-defined research topic include:

Relevance : A research topic should be relevant and significant to the field of study and address a current issue, problem, or gap in knowledge.
Specificity : A research topic should be specific enough to allow for a focused investigation and clear understanding of the research question.
Feasibility : A research topic should be feasible, meaning it should be possible to carry out the research within the given constraints of time, resources, and expertise.
Novelty : A research topic should add to the existing body of knowledge by introducing new ideas, concepts, or theories.
Clarity : A research topic should be clearly articulated and easy to understand, both for the researcher and for potential readers of the research.
Importance : A research topic should be important and have practical implications for the field or society as a whole.
Significance : A research topic should be significant and have the potential to generate new insights and understanding in the field.

Examples of Research Topics

Here are some examples of research topics that are currently relevant and in-demand in various fields:

The impact of social media on mental health: With the rise of social media use, this topic has gained significant attention in recent years. Researchers could investigate how social media affects self-esteem, body image, and other mental health concerns.
The use of artificial intelligence in healthcare: As healthcare becomes increasingly digitalized, researchers could explore the use of AI algorithms to predict and prevent disease, optimize treatment plans, and improve patient outcomes.
Renewable energy and sustainable development: As the world seeks to reduce its carbon footprint, researchers could investigate the potential of renewable energy sources such as wind and solar power, and how these technologies can be integrated into existing infrastructure.
The impact of workplace diversity and inclusion on employee productivity: With an increasing focus on diversity and inclusion in the workplace, researchers could investigate how these factors affect employee morale, productivity, and retention.
Cybersecurity and data privacy: As data breaches and cyber attacks become more common, researchers could explore new methods of protecting sensitive information and preventing malicious attacks.
T he impact of mindfulness and meditation on stress reduction: As stress-related health issues become more prevalent, researchers could investigate the effectiveness of mindfulness and meditation practices on reducing stress and improving overall well-being.

Research Topics Ideas

Here are some Research Topics Ideas from different fields:

The impact of social media on mental health and well-being.
The effectiveness of various teaching methods in improving academic performance in high schools.
The role of AI and machine learning in healthcare: current applications and future potentials.
The impact of climate change on wildlife habitats and conservation efforts.
The effects of video game violence on aggressive behavior in young adults.
The effectiveness of mindfulness-based stress reduction techniques in reducing anxiety and depression.
The impact of technology on human relationships and social interactions.
The role of exercise in promoting physical and mental health in older adults.
The causes and consequences of income inequality in developed and developing countries.
The effects of cultural diversity in the workplace on job satisfaction and productivity.
The impact of remote work on employee productivity and work-life balance.
The relationship between sleep patterns and cognitive functioning.
The effectiveness of online learning versus traditional classroom learning.
The role of government policies in promoting renewable energy adoption.
The effects of childhood trauma on mental health in adulthood.
The impact of social media on political participation and civic engagement.
The effectiveness of cognitive-behavioral therapy in treating anxiety disorders.
The relationship between nutrition and cognitive functioning.
The impact of gentrification on urban communities.
The effects of music on mood and emotional regulation.
The impact of microplastics on marine ecosystems and food webs.
The role of artificial intelligence in detecting and preventing cyberattacks.
The effectiveness of mindfulness-based interventions in managing chronic pain.
The relationship between personality traits and job satisfaction.
The effects of social isolation on mental and physical health in older adults.
The impact of cultural and linguistic diversity on healthcare access and outcomes.
The effectiveness of psychotherapy in treating depression and anxiety in adolescents.
The relationship between exercise and cognitive aging.
The effects of social media on body image and self-esteem.
The role of corporate social responsibility in promoting sustainable business practices.
The impact of mindfulness meditation on attention and focus in children.
The relationship between political polarization and media consumption habits.
The effects of urbanization on mental health and well-being.
The role of social support in managing chronic illness.
The impact of social media on romantic relationships and dating behaviors.
The effectiveness of behavioral interventions in promoting physical activity in sedentary adults.
The relationship between sleep quality and immune function.
The effects of workplace diversity and inclusion programs on employee retention.
The impact of climate change on global food security.
The role of music therapy in improving communication and social skills in individuals with autism spectrum disorder.
The impact of cultural values on the development of mental health stigma.
The effectiveness of mindfulness-based stress reduction techniques in reducing burnout in healthcare professionals.
The relationship between social media use and body dissatisfaction among adolescents.
The effects of nature exposure on cognitive functioning and well-being.
The role of peer mentoring in promoting academic success in underrepresented student populations.
The impact of neighborhood characteristics on physical activity and obesity.
The effectiveness of cognitive rehabilitation interventions in improving cognitive functioning in individuals with traumatic brain injury.
The relationship between organizational culture and employee job satisfaction.
The effects of cultural immersion experiences on intercultural competence development.
The role of assistive technology in promoting independence and quality of life for individuals with disabilities.
The impact of workplace design on employee productivity and well-being.
The impact of digital technologies on the music industry and artist revenues.
The effectiveness of cognitive behavioral therapy in treating insomnia.
The relationship between social media use and body weight perception among young adults.
The effects of green spaces on mental health and well-being in urban areas.
The role of mindfulness-based interventions in reducing substance use disorders.
The impact of workplace bullying on employee turnover and job satisfaction.
The effectiveness of animal-assisted therapy in treating mental health disorders.
The relationship between teacher-student relationships and academic achievement.
The effects of social support on resilience in individuals experiencing adversity.
The role of cognitive aging in driving safety and mobility.
The effectiveness of psychotherapy in treating post-traumatic stress disorder (PTSD).
The relationship between social media use and sleep quality.
The effects of cultural competency training on healthcare providers’ attitudes and behaviors towards diverse patient populations.
The role of exercise in preventing chronic diseases such as type 2 diabetes and cardiovascular disease.
The impact of the gig economy on job security and worker rights.
The effectiveness of art therapy in promoting emotional regulation and coping skills in children and adolescents.
The relationship between parenting styles and child academic achievement.
The effects of social comparison on well-being and self-esteem.
The role of nutrition in promoting healthy aging and longevity.
The impact of gender diversity in leadership on organizational performance.
The effectiveness of family-based interventions in treating eating disorders.
The relationship between social media use and perceived loneliness among older adults.
The effects of mindfulness-based interventions on pain management in chronic pain patients.
The role of physical activity in preventing and treating depression.
The impact of cultural differences on communication and conflict resolution in international business.
The effectiveness of eye movement desensitization and reprocessing (EMDR) in treating anxiety disorders.
The relationship between student engagement and academic success in higher education.
The effects of discrimination on mental health outcomes in minority populations.
The role of virtual reality in enhancing learning experiences.
The impact of social media influencers on consumer behavior and brand loyalty.
The effectiveness of acceptance and commitment therapy (ACT) in treating chronic pain.
The relationship between social media use and body image dissatisfaction among men.
The effects of exposure to nature on cognitive functioning and creativity.
The role of spirituality in coping with illness and disability.
The impact of automation on employment and job displacement.
The effectiveness of dialectical behavior therapy (DBT) in treating borderline personality disorder.
The relationship between teacher-student relationships and school attendance.
The effects of mindfulness-based interventions on workplace stress and burnout.
The role of exercise in promoting cognitive functioning and brain health in older adults.
The impact of diversity and inclusion initiatives on organizational innovation and creativity.
The effectiveness of cognitive remediation therapy in treating schizophrenia.
The relationship between social media use and body dissatisfaction among women.
The effects of exposure to natural light on mood and sleep quality.
The role of spirituality in enhancing well-being and resilience in military personnel.
The impact of artificial intelligence on job training and skill development.
The effectiveness of interpersonal therapy (IPT) in treating depression.
The relationship between parental involvement and academic achievement among low-income students.
The effects of mindfulness-based interventions on emotional regulation and coping skills in trauma survivors.
The role of nutrition in preventing and treating mental health disorders.

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How To Choose A Research Topic

Step-By-Step Tutorial With Examples + Free Topic Evaluator

By: Derek Jansen (MBA) | Expert Reviewer: Dr Eunice Rautenbach | April 2024

Choosing the right research topic is likely the most important decision you’ll make on your dissertation or thesis journey. To make the right choice, you need to take a systematic approach and evaluate each of your candidate ideas across a consistent set of criteria. In this tutorial, we’ll unpack five essential criteria that will help you evaluate your prospective research ideas and choose a winner.

Overview: The “Big 5” Key Criteria

Topic originality or novelty
Value and significance
Access to data and equipment
Time limitations and implications
Ethical requirements and constraints

Criterion #1: Originality & Novelty

As we’ve discussed extensively on this blog, originality in a research topic is essential. In other words, you need a clear research gap . The uniqueness of your topic determines its contribution to the field and its potential to stand out in the academic community. So, for each of your prospective topics, ask yourself the following questions:

What research gap and research problem am I filling?
Does my topic offer new insights?
Am I combining existing ideas in a unique way?
Am I taking a unique methodological approach?

To objectively evaluate the originality of each of your topic candidates, rate them on these aspects. This process will not only help in choosing a topic that stands out, but also one that can capture the interest of your audience and possibly contribute significantly to the field of study – which brings us to our next criterion.

Criterion #2: Value & Significance

Next, you’ll need to assess the value and significance of each prospective topic. To do this, you’ll need to ask some hard questions.

Why is it important to explore these research questions?
Who stands to benefit from this study?
How will they benefit, specifically?

By clearly understanding and outlining the significance of each potential topic, you’ll not only be justifying your final choice – you’ll essentially be laying the groundwork for a persuasive research proposal , which is equally important.

Criterion #3: Access to Data & Equipment

Naturally, access to relevant data and equipment is crucial for the success of your research project. So, for each of your prospective topic ideas, you’ll need to evaluate whether you have the necessary resources to collect data and conduct your study.

Here are some questions to ask for each potential topic:

Will I be able to access the sample of interest (e.g., people, animals, etc.)?
Do I have (or can I get) access to the required equipment, at the time that I need it?
Are there costs associated with any of this? If so, what are they?

Keep in mind that getting access to certain types of data may also require special permissions and legalities, especially if your topic involves vulnerable groups (patients, youths, etc.). You may also need to adhere to specific data protection laws, depending on the country. So, be sure to evaluate these aspects thoroughly for each topic. Overlooking any of these can lead to significant complications down the line.

Free Webinar: How To Find A Dissertation Research Topic

Criterion #4: Time Requirements & Implications

Naturally, having a realistic timeline for each potential research idea is crucial. So, consider the scope of each potential topic and estimate how long each phase of the research will take — from literature review to data collection and analysis, to writing and revisions. Underestimating the time needed for a research project is extremely common , so it’s important to include buffer time for unforeseen delays.

Remember, efficient time management is not just about the duration but also about the timing . For example, if your research involves fieldwork, there may specific times of the year when this is most doable (or not doable at all). So, be sure to consider both time and timing for each of your prospective topics.

Criterion #5: Ethical Compliance

Failing to adhere to your university’s research ethics policy is a surefire way to get your proposal rejected . So, you’ll need to evaluate each topic for potential ethical issues, especially if your research involves human subjects, sensitive data, or has any potential environmental impact.

Remember that ethical compliance is not just a formality – it’s a responsibility to ensure the integrity and social responsibility of your research. Topics that pose significant ethical challenges are typically the first to be rejected, so you need to take this seriously. It’s also useful to keep in mind that some topics are more “ethically sensitive” than others , which usually means that they’ll require multiple levels of approval. Ideally, you want to avoid this additional admin, so mark down any prospective topics that fall into an ethical “grey zone”.

If you’re unsure about the details of your university’s ethics policy, ask for a copy or speak directly to your course coordinator. Don’t make any assumptions when it comes to research ethics!

Key Takeaways

In this post, we’ve explored how to choose a research topic using a systematic approach. To recap, the “Big 5” assessment criteria include:

Topic originality and novelty
Time requirements
Ethical compliance

Be sure to grab a copy of our free research topic evaluator sheet here to fast-track your topic selection process. If you need hands-on help finding and refining a high-quality research topic for your dissertation or thesis, you can also check out our private coaching service .

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How to Select a Research Topic: A Step-by-Step Guide

by Antony W

June 6, 2024

Learning how to select a research topic can be the difference between failing your assignment and writing a comprehensive research paper. That’s why in this guide we’ll teach you how to select a research topic step-by-step.

You don’t need this guide if your professor has already given you a list of topics to consider for your assignment . You can skip to our guide on how to write a research paper .

If they have left it up to you to choose a topic to investigate, which they must approve before you start working on your research study, we suggest that you read the process shared in this post.

Choosing a topic after finding your research problem is important because:

The topic guides your research and gives you a mean to not only arrive at other interesting topics but also direct you to discover new knowledge
The topic you choose will govern what you say and ensures you keep a logical flow of information.

Picking a topic for a research paper can be challenging and sometimes intimidating, but it’s not impossible. In the following section, we show you how to choose the best research topic that your instructor can approve after the first review.

How to Select a Research Topic

Below are four steps to follow to find the most suitable topic for your research paper assignment:

Step 1: Consider a Topic that Interests You

If your professor has asked you to choose a topic for your research paper, it means you can choose just about any subject to focus on in your area of study. A significant first step to take is to consider topics that interest you.

An interesting topic should meet two very important conditions.

First, it should be concise. The topic you choose should not be too broad or two narrow. Rather, it should be something focused on a specific issue. Second, the topic should allow you to find enough sources to cite in the research stage of your assignment.

The best way to determine if the research topic is interesting is to do some free writing for about 10 minutes. As you free write, think about the number of questions that people ask about the topic and try to consider why they’re important. These questions are important because they will make the research stage easier for you.

You’ll probably have a long list of interesting topics to consider for your research assignment. That’s a good first step because it means your options aren’t limited. However, you need to narrow down to only one topic for the assignment, so it’s time to start brainstorming.

Step 2: Brainstorm Your Topics

You aren’t doing research at this stage yet. You are only trying to make considerations to determine which topic will suit your research assignment.

The brainstorming stage isn’t difficult at all. It should take only a couple of hours or a few days depending on how you approach.

We recommend talking to your professor, classmates, and friends about the topics that you’ve picked and ask for their opinion. Expect mixed opinions from this audience and then consider the topics that make the most sense. Note what topics picked their interest the most and put them on top of the list.

You’ll end up removing some topics from your initial list after brainstorming, and that’s completely fine. The goal here is to end up with a topic that interests you as well as your readers.

Step 3: Define Your Topics

Check once again to make sure that your topic is a subject that you can easily define. You want to make sure the topic isn’t too broad or too narrow.

Often, a broad topic presents overwhelming amount of information, which makes it difficult to write a comprehensive research paper. A narrow topic, on the other hand, means you’ll find very little information, and therefore it can be difficult to do your assignment.

The length of the research paper, as stated in the assignment brief, should guide your topic selection.

Narrow down your list to topics that are:

Broad enough to allows you to find enough scholarly articles and journals for reference
Narrow enough to fit within the expected word count and the scope of the research

Topics that meet these two conditions should be easy to work on as they easily fit within the constraints of the research assignment.

Step 4: Read Background Information of Selected Topics

You probably have two or three topics by the time you get to this step. Now it’s time to read the background information on the topics to decide which topic to work on.

This step is important because it gives you a clear overview of the topic, enabling you to see how it relates to broader, narrower, and related concepts. Preliminary research also helps you to find keywords commonly used to describe the topic, which may be useful in further research.

It’s important to note how easy or difficult it is to find information on the topic.

Look at different sources of information to be sure you can find enough references for the topic. Such periodic indexes scan journals, newspaper articles, and magazines to find the information you’re looking for. You can even use web search engines. Google and Bing are currently that best options to consider because they make it easy for searchers to find relevant information on scholarly topics.

If you’re having a hard time to find references for a topic that you’ve so far considered for your research paper, skip it and go to the next one. Doing so will go a long way to ensure you have the right topic to work on from start to finish.

Get Research Paper Writing Help

If you’ve found your research topic but you feel so stuck that you can’t proceed with the assignment without some assistance, we are here to help. With our research paper writing service , we can help you handle the assignment within the shortest time possible.

We will research your topic, develop a research question, outline the project, and help you with writing. We also get you involved in the process, allowing you to track the progress of your order until the delivery stage.

About the author

Antony W is a professional writer and coach at Help for Assessment. He spends countless hours every day researching and writing great content filled with expert advice on how to write engaging essays, research papers, and assignments.

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Inhaltsverzeichnis

1 Definition: Research Topics
3 Finding Research Topics
4 Defining Good Research Topics
5 Academic Writing Research Topics
6 Examples of Research Topics
7 In a Nutshell

Definition: Research Topics

A research topic is the subject or issue that forms the basis of a research paper. It is a well-defined subject the researcher is interested in. While it can be phrased as a question, you are not required to do so. The research then addresses the question. It can also be phrased both as a research question and a hypothesis.

The purpose of this article is to help you understand what research topics are and how they are used to conduct good research. It covers the characteristics of good research topics and provides information on and techniques for coming up with good research topics. The importance of research topics in academic writing is explained and some examples of research topics are listed.

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How do you come up with ideas for suitable research topics?

Rational thinking and creative techniques are two key methods you can use to generate research ideas. You can use either of the techniques, or you can try both techniques and then decide which one you find more useful for your research. Both concepts are further discussed later in this article.

Tip: Keep in mind that you’ll need to create research questions based on your topic later on. It’s ok to begin with vague ideas, but later on you need to focus on a specific area of a topic.

How do you refine your research topic ideas?

The Delphi technique is an approach that many students have found useful for refining their research ideas. Usually, a number of people who are interested in the research are assembled to help generate and select more refined research topics. The next step will be to refine your ideas into a research question . This will require you to conduct more research on topics or issues that you found interesting during the research topic deciding phase.

What are the main elements of a research proposal?

A research proposal consists of an appropriate title that mirrors the content of the proposal; a background to justify the need for the research; a statement on what the research is meant to achieve. A section should be dedicated to the methods that will be adopted in order to achieve the research objectives within the expected timeframe. A section on resource considerations will help convince the reader about the feasibility of the research. This should be followed by a list of references.

How do you propose research topics?

Writing helps organize our ideas into coherent statements. For inspiration, check out some research proposal examples . The draft proposal should be discussed with your thesis supervisor or teaching assistant, who can advise you on how the proposal might be amended if necessary, so that the research can be completed within the proposed timeframe. This is of particular importance if the proposal has to be presented for funding or to an academic research committee for approval.

What defines a good research topic?

You’re the one who has to write the research paper or thesis, so it’s vital that YOU are interested in the topic that you’re researching. Your research topic shouldn’t be too vague. But in saying that, you also need to ensure that you’re able to write about your topic within the time frame provided. You need to be able to formulate your topic into a research question and a thesis statement later on.

Finding Research Topics

If done using a systematic approach, finding research topics can be interesting. A range of techniques involving rational as well as creative thinking are used to find a research topic.

Brainstorming

This is a problem-solving technique which generates best results when carried out as a group, but it can also be done by an individual. Find a quiet place to work and write down a problem related to your lectures or curriculum that interests you and of which you have some prior knowledge.

If you are working in a group, members can make suggestions regarding the problem. Make a note of all the suggestions and include all contributions, however wild they may be. Review each of the suggestions with your group and select the ones that most appeal to you. You may arrange discussing these suggestions with your thesis supervisor or the teaching assistant in charge of your project if needed.

Inspiration from your teachers

Project leaders, teaching assistants, professional groups and practitioners in your field will often have project ideas they are happy to share. They might come up with good research topics; just be sure to document the ideas discussed so that you can remember to further explore them on your own.

Literature search

Articles, reports in academic journals and books are all useful sources of research topics. Review articles in particular often indicate areas in which more research may be required. Most recently published reports usually contain recommendations which can form the basis of further research, and books contain an overview of research already undertaken, in addition to suggesting new areas to explore for further research.

Relevance trees

This technique involves generating topics on the basis of a broad concept. Each of these topics constitutes an independent branch which can yield sub-branches. You can review these sub-branches and combine some of them to come up with new research topics. Your project supervisor or teaching assistant may be of help in selecting a final topic from the shortlisted ones if you cannot narrow your choice down to one topic.

Looking inwards

Another way of finding a research topic is to review the assignments you have already completed and select the ones you received good grades in. These are the ones in which you are already knowledgeable. They will provide you with possibilities for further research.

Defining Good Research Topics

A good research topic should have well defined objectives. Selecting a research topic which you will be interested in for the entire research duration is vital. If you have only a vague interest in the topic, it will be difficult to excel on such a topic. Therefore, you should have a genuine interest in the research topic you have chosen.

Make sure you possess the required skills and resources, or that you can develop the capability that is necessary to research the topic within the given timeframe. You should also be certain that you can access the data you will need to collect in the course of the research. Your research topic should be one you are familiar with and in which you have the capacity to produce a well-written final research report.

TIP: Always use transition words to properly connect the sentences and paragraphs in your thesis or essay.

Academic Writing Research Topics

Academic writing is a style of expression that defines the intellectual boundaries of a discipline. It focuses on a research problem and conveys an accepted interpretation of concepts or complex ideas. Research topics are germane to academic writing because they proffer rigorous arguments that can convince a reader to reconsider previously accepted position on a topic.

Examples of Research Topics

Previous research topics can serve as sources of inspiration for finding new research topics. Some examples of different research topics include: • Media and communications research paper topics • Environmental research paper topics • Business research paper topics

Depending on your field of study, looking at past projects can be very helpful in your search for new research topics.

In a Nutshell

A research topic is a well-defined subject the researcher is interested in.
Rational thinking and creative techniques are two methods you can use to generate research ideas.
Techniques to find good research topics include brainstorming, getting inspiration from your teachers, using relevance trees, doing a literature search or looking inwards.
You should have a genuine interest in the research topic you have chosen.

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Research Papers

How to Find a Topic for Your Research Paper

Last Updated: September 12, 2023 References

This article was co-authored by Matthew Snipp, PhD and by wikiHow staff writer, Jennifer Mueller, JD . C. Matthew Snipp is the Burnet C. and Mildred Finley Wohlford Professor of Humanities and Sciences in the Department of Sociology at Stanford University. He is also the Director for the Institute for Research in the Social Science’s Secure Data Center. He has been a Research Fellow at the U.S. Bureau of the Census and a Fellow at the Center for Advanced Study in the Behavioral Sciences. He has published 3 books and over 70 articles and book chapters on demography, economic development, poverty and unemployment. He is also currently serving on the National Institute of Child Health and Development’s Population Science Subcommittee. He holds a Ph.D. in Sociology from the University of Wisconsin—Madison. This article has been viewed 98,667 times.

Sometimes, finding a topic for a research paper can be the most challenging part of the whole process. When you're looking out at a field brimming with possibilities, it's easy to get overwhelmed. Lucky for you, we here at wikiHow have come up with a list of ways to pick that topic that will take you from the more vague brainstorming all the way to your specific, perfectly focused research question and thesis.

Review your course materials.

Your textbook, syllabus, and class notes can help you find a topic.

If your textbook has discussion questions at the end of each chapter, these can be great to comb through for potential research paper topic ideas.
Look at any recommended reading your instructor has suggested—you might find ideas there as well.

Search hot issues in your field of study.

Run an internet search or talk to your instructor.

Think about current events that touch on your field of study as well. For example, if you're writing a research paper for a sociology class, you might want to write something related to race in America or the Black Lives Matter movement.
Other instructors in the same department or field might also have ideas for you. Don't be afraid to stop in during their office hours and talk or send them an email, even if you've never had them for a class.

Go for a walk to get your brain going.

Being active can stimulate your mind to focus on topic ideas.

If you want to walk with a friend and discuss topic ideas as you walk, that can help too. Sometimes, you'll come up with new things when you can bounce your ideas off someone else.

Ask your family or friends for input.

Bounce ideas off of people you know to get their thoughts.

People who aren't really familiar with the general subject you're researching can be helpful too! Because they aren't making many assumptions, they might bring up something you'd overlooked or not thought about before.

Free-write on topic ideas to find your passion.

Set a timer for 5 or 10 minutes and write without stopping.

Having a personal interest in the topic will keep you from getting bored. You'll do better research—and write a better paper—if you're excited about the topic itself.

Read background information on your favorites.

Search online for background articles about topics you like.

Ideally, based on your background research, you'll be able to choose one of the topics that interests you the most. If you still can't narrow it down, keep reading!
Even though you wouldn't want to use them as sources for your actual paper, sources like Wikipedia can be excellent for getting background information about a topic.

Identify important words to use as keywords.

Jot down words related to your topic to search for sources.

For example, if you've chosen environmental regulations as a topic, you might also include keywords such as "conservation," "pollution," and "nature."

Do preliminary research using your keywords.

Search online or on library databases and review your results.

Your results might also suggest other keywords you can search to find more sources. Searching for specific terminology used in articles you find often leads to other articles.
Check the bibliography of any papers you find to pick up some other sources you might be able to use.

Limit a broad topic.

Narrow your topic to a specific time period, geographic area, or population.

For example, suppose you decided to look at race relations in the US during the Trump administration. If you got too many results, you might narrow your results to a single US city or state.
Keep in mind how long your research paper will ultimately be. For example, if there's an entire book written on a topic you want to write a 20-page research paper on, it's probably too broad.

Expand a topic that's too narrow.

Broaden your scope if you're not getting enough results from your keywords.

For example, suppose you wanted to research the impact of a particular environmental law on your hometown, but when you did a search, you didn't get any quality results. You might expand your search to encompass the entire state or region, rather than just your hometown.

Do more in-depth research to fine-tune your topic.

Run another search based on the information you've gained.

For example, you might do an initial search and get hundreds of results back and decide your topic is too broad. Then, when you limit it, you get next to nothing and figure out you've narrowed it too much, so you have to broaden it a little bit again.
Stay flexible and keep going until you've found that happy medium that you think will work for your paper.

Formulate the question you'll answer in your paper.

Use the 5 W's (who, what, when, where, and why) to write your question.

For example, your research question might be something like "How did environmental regulations affect the living conditions of people living near paper mills?" This question covers "who" (people living near paper mills), "what" (living conditions), "where" (near paper mills), and "why" (environmental regulations).

Build a list of potential sources.

Write down citation information as you work.

At this point, your list is still a "working" list. You won't necessarily use all the sources you find in your actual paper.
Building a working list of sources is also helpful if you want to use a source and can't immediately get access to it. If you have to get it through your professor or request it from another library, you have time to do so.

Develop your thesis.

Your thesis is the answer to your research question.

For example, suppose your research question is "How did environmental regulations affect the living conditions of people living near paper mills?" Your thesis might be something like: "Environmental regulations improved living conditions for people living around paper mills."
As another example, suppose your research question is "Why did hate crimes spike in the US from 2017 to 2020?" Your thesis might be: "A permissive attitude towards racial supremacy caused a spike in hate crimes in the US from 2017 to 2020."
Keep in mind, you don't have to prove that your thesis is correct. Proving that your thesis was wrong can make for an even more compelling research paper, especially if your thesis follows conventional wisdom.

Expert Q&A

If you've been given a list of topics but you come up with something different that you want to do, don't be afraid to talk to your instructor about it! The worst that will happen is that they'll make you choose something from the list instead. [11] X Trustworthy Source Purdue Online Writing Lab Trusted resource for writing and citation guidelines Go to source Thanks Helpful 0 Not Helpful 0

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My Speech Class

Public Speaking Tips & Speech Topics

717 Good Research Paper Topics

Jim Peterson has over 20 years experience on speech writing. He wrote over 300 free speech topic ideas and how-to guides for any kind of public speaking and speech writing assignments at My Speech Class.

good and interesting research paper topics

Some examples of common research paper styles include:

Argumentative Research Papers
Persuasive Research Papers
Education Research Papers
Analytical Research Papers
Informative Research Papers

Your research essay topic may also need to be related to the specific class you are taking. For example, an economics class may require a business research paper, while a class on human behavior may call for a psychology research paper.

The requirements for your paper will vary depending on whether you are in high school, college, or a postgraduate student. In high school, you may be able to choose an easy topic and cite five or six sources you found on Google or Yahoo!, but college term papers require more in-depth research from reliable sources, such as scholarly books and peer-reviewed journals.

Do you need some help with brainstorming for topics? Some common research paper topics include abortion, birth control, child abuse, gun control, history, climate change, social media, AI, global warming, health, science, and technology.

But we have many more!

On this page, we have hundreds of good research paper topics across a wide range of subject fields. Each of these topics could be used “as is” to write your paper, or as a starting point to develop your own topic ideas.

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How to Choose Your Research Paper Topic

The first step to developing an interesting research paper is choosing a good topic. Finding a topic can be difficult, especially if you don’t know where to start. Finding the Right Research Paper Topic

If you are in a class that allows you to choose your own term paper topic, there are some important areas to consider before you begin your project:

Your Level of Interest: Research papers are time-consuming; you will be spending countless hours researching the topic and related topics, developing several primary and secondary sources, and putting everything together into a paper that is coherent and accomplishes your objectives. If you do not choose a topic you are passionate about, the process will be far more tedious, and the finished product may suffer as a result.

Your Level of Experience: Being interested in a topic is great, but it is even more helpful if you already know something about it. If you can find a topic that you already have some personal and/or professional experience with, it will vastly reduce the amount of research needed and make the whole process much easier.

Available Information on the Topic: Be sure to choose a topic that is not only interesting but also one that has numerous sources available from which to compile your research. A researchable topic with several potential sources gives you access to the level of information you need to become an authority on the subject.

Your Audience: An interesting topic to you may not necessarily be interesting to your professor or whoever is grading your research paper. Before you begin, consider the level of interest of the person(s) who will be reading it. If you are writing a persuasive or argumentative essay, also consider their point of view on the subject matter.

As you begin researching your topic, you may want to revise your thesis statement based on new information you have learned. This is perfectly fine, just have fun and pursue the truth, wherever it leads. If you find that you are not having fun during the research phase, you may want to reconsider the topic you have chosen.

The process of writing the research paper is going to be very time consuming so it’s important to select a topic that is going to sustain your interest for the duration of the project. It is good to select a topic that is relevant to your life since you are going to spend a long time researching and writing about it. Perhaps you are considering starting your own business or pursuing a career in politics. Look through the suggested research paper topics and find one in a category that you can relate to easily. Finding a topic that you have some personal interest in will help make the arduous task a lot easier, and the project will have better results because of your vested interest.

Our List of Research Topics and Issues

Affirmative action, health, pharmacy, medical treatments, interpersonal communication, marketing and advertising, barack obama, discrimination, bill clinton, hilary clinton, computer crimes and security, cosmetic surgery, controversial, criminal justice, donald trump, easy/simple, environment, family violence, foreign policy, gambling and lotteries, the lgbtq community, generational conflict, gun control, hate crimes, immigration, middle east, maternity/paternity leave, natural disasters, police work, population explosion, pornography, prisons and prisoners, prostitution, ronald reagan, student loan debt, teen issues, women, mothers, what, why, and how, relationships.

We compiled an exhaustive list of topics that would make excellent research papers. The topics are specifically organized to help you find one that will work for your project. Broad topics are headed, and then below them are narrowed topics, all to help you find an area to focus on. The way we have organized the topics for research papers can save you lots of time getting prepared to write your research paper.

We have topics that fit into categories that cover such areas as education, environmental sciences, communication and languages, current events, politics, business, criminal justice, art, psychology, economics to name just a few. Simply get started by choosing the category that interests you and peruse through the topics listed in that category and you’ll be well on your way to constructing an excellent research paper.

Be sure to check other topics ideas: persuasive speech topics , argumentative speech topics , policy speech topics . We also have some sample outlines and essay templates .

What limits are responsible?
What limits are realistic?
How to protect abortion doctors, pregnant women, and the protection of abortion clinics vs. the right to protest
Partial birth abortion
Scientific evidence vs. definition of viability
Stem cell research
Unborn victims of violence
Relative equality has been achieved vs. serious inequities continue
Can racial balance in business, education, and the military be achieved without policies that promote Affirmative Action
Reverse discrimination
NOW, National Organization for Women
No government support vs. fairness to parents who pay twice for education
Separation of church and state vs. religion’s contribution to the public good
Placement by age vs. placement by academic ability
Mainstreaming students with disabilities vs. special classrooms for their special needs
Required standardized tests for advancement vs. course requirements only
National standardized tests vs. local control of education
Discrimination in education
Multicultural/bilingual education vs. traditional basics
Teacher competency tests vs. degree requirements only
Teacher’s needs/demands vs. teaching as a service profession
Policing schools
School’s responsibility vs. parental responsibility for school violence
Drug and alcohol abuse, pregnancy, suicide
Zero tolerance toward violence vs. toughness with flexibility
Permit corporal punishment
Exams often do little more than measure a person’s ability to take exams. Should exams be outlawed in favor of another form of assessment?
Should teens in the U.S. adopt the British custom of taking a “gap year” between high school and college?
In some European schools, fewer than 10% of students get “As”. Is there grade inflation in the U.S.? Why so many “As” for Americans?
Education and funding
Grade inflation
No Child Left Behind Act: Is it working?
Home schooling
Standardized tests
Are children smarter (or more socialized) because of the Internet?
Should the federal government be allowed to regulate information on the internet?
How has the music industry been affected by the internet and digital downloading?
How does a search engine work?
What are the effects of prolonged steroid use on the human body?
What are the benefits and hazards of medical marijuana?
How does tobacco use affect the human body?
Do the benefits of vaccination outweigh the risks?
What are some common sleep disorders and how are they treated?
What are the risks of artificial tanning or prolonged exposure to the sun?
Should thin people have to pay Medicare and other health costs for the health problems of obese people? Should obese people have higher premiums?
Low carbohydrate vs. low fat diets
Benefits of weight training vs. aerobics
How much weekly exercise is needed to achieve lasting health benefits
Health websites give too much information
Psychological disorders, such as cutting and self-harm, eating disorders, Autism, Tourette Syndrome, ADHD, ADD, Asperger Syndrome
Are we taking it too far by blaming fast food restaurants for obesity? When is it individual responsibility and when is it appropriate to place blame?
Should companies allow employees to exercise on work time?
Steroids, Antibiotics, Sprays; Are food manufacturers killing us?
Alternative medicine
Alzheimer’s disease
Causes of eating disorders, society’s portrayal of women
Eating disorders statistics
Down’s syndrome
Birth control
Dietary supplements
Exercise and fitness
Heart disease
In vitro fertilization
Attention deficit disorder
Investigate the history and authenticity of ADHD and ADD.
Organic foods
Prescription drugs
Vegetarianism
Learning disabilities
Schizophrenia
Coma recovery: techniques, successes, new strategies.
What are the primary types of cancer, and in what ways are they related?
Investigate the success ratio of holistic and non-medical cancer treatments.
Is Alzheimer’s inevitable? Examine theories regarding its prevention.
What forms of physical degeneracy are seen as linked to aging?
Investigate the connections between emotional stability and physical well-being, and provide evidence as to how the two may be related.
Investigate differences in rates of injury recovery and overcoming illness based on cultural parameters.
Examine the modern history of viral epidemics, researching what is known about the emergence of deadly viruses.
Examine how congenital heart disease may be treated, and how it differs from other forms of heart disease.
Is occasional depression a natural state to an extent, and is society too eager to treat this as a disorder?
Investigate Sociopathy, determine biological and psychological roots, typical patterns, and potentials of treatment.
How are compulsive behaviors determined as such? Explore examples of anal retention and expulsion, OCD, etc., as offering accepted criteria.
Research and analyze the nature of codependency as both a normal state of relations and as an unhealthy extreme.
Investigate the history and practice of electroshock, analyzing how and why this extreme treatment came to be widely used.
Hoarding: symptoms and treatments, causes, types of hoarding
Limits on extraordinary, costly treatments vs. doing everything possible
Nutritional/alternative therapy vs. mainstream medical treatment insurance coverage for alternative treatment?
Government grants for alternative treatment research?
Health superiority of alternative treatments?
Assisted suicide vs. preservation of life
Governmental insurance requirements
Should there be a national database to track controlled substances (i.e., OXYCODONE) or should it be a state issue?
Should parents avoid vaccinating their children?
Decline of communication due to technology
Online social networks and their influence
Impact of texting and cell phones
How do men and women communicate differently using body language, and why does it matter (in dating, the workplace, and social circles)?
Limitations of the media
Marketing to children
Sexual innuendos in marketing
Global marketing trends
Should certain kinds of ads be banned in the interest of health/morality/annoyance – alcohol, cigarettes, prescription meds, etc…?
Children’s programming and advertising
Most controversial political ads
Media response and public outcry to political ads
Campaign funds and their relation to political advertising
Domestic policy
Separation of church and state
Judge nominations and make up of supreme court
Congressional opposition to presidential nominees/filibusters
Affirmative action
Erosion of civil liberties vs. protection against terrorism
Patriot Act One and Two
Most developed nations have universal health coverage. Why doesn’t the U.S., the wealthiest nation, have it?
Tax cut as economic stimulation
Needs of the states vs. needs of the individuals
Budget deficits and deficit spending
Rich vs. poor
Protection of victims vs. freedom of speech/rights of the accused
How to improve race relations
Women still earn only 75 cents for every $1 a man earns. Explain why.
Discrimination in the workplace: analyzing issues for today’s corporations.
Gender discrimination
Interracial marriage
Should government impose restrictions on what kinds of foods can be served in school cafeterias?
Pros and cons of school uniforms.
Do children learn better in boys-only and girls-only schools?
Charter schools
Prayer in schools
Rights of the individual vs. community safety (or campus safety)
Funding for research
U.S. obligation to third world countries
Manufacturing of generic drugs vs. U.S. pharmaceutical companies
How contagious diseases “jump” from animal hosts to human
What treatments are available to people infected with HIV and are they effective?
Right to privacy of a child with AIDS vs. safety of other children
Limits for campus safety vs. personal freedom
Implications on violence and crime
Issues with binge drinking
Should the U.S. lower the drinking age to 18?
Leniency because of condition vs. community safety
Revoking drivers license vs. being able to attend classes and work
Age discrimination of violators
Animal rights vs. medical research
Should it be illegal to use animals for sports and entertainment?
Humane treatment of animals vs. factory farms
Animal welfare in slaughter houses
Animal protection vs. business, employment interests
School prestige vs. academic standards
Should shoe companies be able to give away free shoes and equipment to high school athletes?
Should college athletes be paid?
Doping in sports
What are the effects on children whose parents push them in sports?
Steroids: Should they be legalized?
Title IX: Has it helped women’s sports? Has it harmed men’s sports?
Social effects of team sports
Needed in public school library/curriculum?
Needed in entertainment industry?
Needed on the Internet?
Should parents censor textbooks and other literature for children in schools?
Parental filters on the Internet. Does censorship actually increase curiosity and use of pornography?
How is internet censorship used in China and around the world?
How has United States censorship changed over the decades?
Democratic kingmaker, influence on political succession
Impact of global initiative
Influence on fundraising
Influence as Secretary of State
Foreign policies
Influence on women
ACT or SAT score requirements
Promotional techniques, such as 1st time scholarships
4 year vs. 2 year colleges
College admission policies
College tuition planning
Distance education
Diploma mills
Online porn vs. freedom of speech
Stalking, invasion of privacy vs. reasonable access
Hacking crimes–workable solutions?
What are the latest ways to steal identity and money?
From where does spam email come and can we stop it?
How do computer viruses spread and in what ways do they affect computers?
Cyber security
Securing Internet commerce: is it possible in today’s arms’ race of hackers and evolving technology?
Is downloading of media (music, videos, software) infringing on the rights of media producers and causing economic hardships on media creators?
Should media producers prosecute students and individuals that they suspect of downloading copyrighted materials?
Programs such as SPOTIFY and PANDORA
Copyright Law
Age limitations on surgery
Addiction to surgery
Demand for beauty by society
The dangers of breast implants for teenagers
The cost of cosmetic surgery
Plastic surgery
Weight loss surgery
Are surgeons “scissor happy,” and are surgeries widely unnecessarily
Negative texting, instant messaging, email
Is cyber-bullying as bad as face-to-face?
Kinds of punishment for cyber-bullying
Media response
Should the state or federal government put laws into place to prevent bullying?
Is homosexuality a choice, or are people born gay?
Evolution vs. Creationism.
Should “under God” remain in the Pledge of Allegiance?
Is healthcare a right or a privilege?
Fossil fuels vs. alternative energy.
Transgender bathroom policies.
Capitalism vs. socialism.
Should parents be allowed to spank their children?
Should sanctuary cities lose their federal funding?
The pros and cons of gun control.
Should the U.S. continue drone strikes in foreign countries?
Was the U.S. justified in going to war with Iraq?
How to solve the Israeli-Palestinian conflict.
The pros and cons of animal testing.
Do pro athletes have the right to sit during the national anthem?
Incarceration rates in the U.S.
Technology and the criminal justice system.
Police brutality and minorities.
Should the police wear body cameras?
In what circumstances should the death penalty be allowed?
Should we have stiffer penalties for drunk driving?
Should those who text while driving be put in jail?
White-collar crime and punishment.
Criminalizing protests and activism.
The rise of wrongful convictions.
Mutual consent vs. exploitation
Campuses with “no touch” policy
Drugs associated to Date Rape
Violence and Rape
Government support vs. parental financing
Benefits vs. harmful effects
Trump’s unconventional presidential campaign.
The psychology of Donald Trump.
Who is behind Trump’s political rise?
Donald Trump and evangelical voters.
Donald Trump the businessman.
Trump’s war on the press (aka “fake news”).
The Trump Organization and conflicts of interest.
The border wall and illegal immigration policy.
Global warming and climate change policy.
Trump-Russia collusion.
The rapid rise of “The Resistance.”
Trump’s legislative agenda; e.g., health care, tax policy, deregulation, etc.
Trump’s “America First” trade and foreign policy.
The case for (or against) the Trump presidency.
Punishment vs. treatment
Family reactions
Social acceptance
Community safety vs. legalization
United States military involvement in Colombian drug trade?
Drug legalization
Abstinence Program: Do they work?
Should the federal government legalize the use of marijuana?
What is the true key to happiness?
What is the cause of America’s obesity crisis?
Why sleep is necessary.
Are plastic bottles really bad for you?
How to encourage people to recycle more.
How 3D printers benefit everyone.
How do GPS systems on smartphones work?
How have oil spills impacted the environment?
Verbal vs. nonverbal communication.
The accuracy of lie detector tests.
How Bill Gates and Steve Jobs changed the world.
The pros and cons of hitchhiking.
The PC vs. the Mac.
What causes tornadoes?
Pollution, air, and water
Endangered species
What are the risks of climate change and global warming?
Rain forests
Alternative energy
Alternative fuel/hybrid vehicles
Conservation
Deforestation
Greenhouse effect
Marine pollution
How have oil spills affected the planet and what steps are being taken to prevent them?
Sustainability of buildings
Recycling programs
Cost of “green” programs
Wind turbines
Landfill issues
Renewable fuels
Radioactive waste disposal
Soil pollution
Wildlife conservation: what efforts are being taken to protect endangered wildlife?
Excessive burden on industries?
Drilling for oil in Alaska’s ANWR (Arctic National Wildlife Refuge)
Gasoline consumption vs. SUV’s popularity
Wildlife protection vs. rights of developers
Clean air and water standards–weakened vs. strengthened
What are the dangers of scuba diving and underwater exploration?
Should the use of coal be subjected to stricter environmental regulations than other fuels?
Is global warming a hoax? Is it being exaggerated?
How much is too much noise? What, if anything, should we do to curb it?
Protecting victims vs. rights of the accused
Women who kill abusive husbands vs. punishment for murder
Marital rape?
How to protect children vs. respect for parental rights
Children who kill abusive parents
Child abuse–workable solutions?
Child abuse
Domestic abuse
Organic farming vs. mainline use of chemical sprays
How to best protect the environment; conservation
Family vs. corporate farms
Food production costs
Interventionism?
Third world debt and World Bank/International Monetary Fund
Military support vs. economic development of third world countries
Human rights violations
European Union in competition with the U.S.
Unilateralism
Relevance of the United Nations
Neocon role in foreign policy
Christian right influence on foreign policy
Pentagon vs. State Department
Nation building as a policy
Arms control
Obama’s National Strategy for Counterterrorism
Control of al Qaeda
Drawdown of U.S. Armed Forces in the Middle East
Cats vs. dogs: which makes the better pet?
My pet can live forever: why I love animal clones.
According to my social media profile, my life is perfect.
Football vs. baseball: which sport is America’s favorite pastime?
Starbucks vs. Caribou: whose coffee is better?
What does your dog really think of you?
Why millennials deserve lower pay.
What makes people end up with so many mismatched socks?
How to become a research paper master.
How reading Tuesdays with Morrie can make you wiser.
Easy way to earn revenues vs. social damage
Individual freedom vs. social damage
Do lotteries actually benefit education or is it a scam?
Can gamblers ever acquire a statistical advantage over the house in casino games?
Should there be a constitutional amendment that allows gays and lesbians to legally marry?
Adoption rights?
Need special rights for protection?
College campus response
Gay, lesbian, bisexual, or transgender
Gay parenting
Elderly to share in the tax burden vs. government support of elderly
Future of social security
Job discrimination
Child rearing
Employment issues
Generational differences
Community and police safety vs. unrestricted right to bear arms
NRA (National Rifle Association)
2nd Amendment
Do states that allow citizens to carry guns have higher or lower crime rates?
Community safety vs. freedom of Speech
Punishment inequities
Persecution of alternative lifestyles
Church Arson: Hate crime?
Prevention of hazing
Greek organizations and rituals of hazing
Statistics of death or injury due to Hazing
High Schools and Hazing
What happened during the Salem witch trials?
How did trains and railroads change life in America?
What may have occurred during the Roswell UFO incident of 1947?
What Olympic events were practiced in ancient Greece?
How did Cleopatra come to power in Egypt? What did she accomplish during her reign?
What are the origins of the conflict in Darfur?
What was the women’s suffrage movement and how did it change America?
How was the assassination of Abraham Lincoln plotted and executed?
How did Cold War tension affect the US and the world?
What happened to the lost settlers at Roanoke?
How did Julius Caesar affect Rome?
How did the Freedom Riders change society?
What was the code of the Bushido and how did it affect samurai warriors?
How did Joan of Arc change history?
What dangers and hardships did Lewis and Clark face when exploring the Midwest?
How are the Great Depression and the Great Recession similar and different?
What was the Manhattan Project and what impact did it have on the world?
Why did Marin Luther protest against the Catholic Church?
How did the Roman Empire fall?
How did the black plague affect Europe?
How did Genghis Khan conquer Persia?
How did journalists influence US war efforts in Vietnam?
Who is Vlad the Impaler and what is his connection to Count Dracula?
Who was a greater inventor, Leonardo di Vinci or Thomas Edison?
What was the role of African Americans during the Revolutionary War?
What was Britain’s view of India during British rule?
What were the factors in the China-Tibet conflict?
Research and analyze the emergence of the Catholic Church as a political force following the collapse of the Roman Empire.
Investigate Dr. Eileen Powers’ claim that the Roman Empire was lost primarily due to an inability to perceive itself as subject to the change inevitable to all governments, or her “force of nature” theory.
Explore and discuss the actual cooperation occurring through the centuries of Barbarian conquest of Rome.
Examine the differences and similarities between Western and Eastern concepts and practices of kingship.
Investigate and explain the trajectory of ALEXANDER THE GREAT’s empire, with minimal emphasis on personal leadership.
To what extent did commerce first link Eastern and Western cultures, and how did this influence early international relations?
Research and analyze how Japan moved from a feudalistic to a modern state, and how geographic isolation played a role in the process.
Analyze the process and effects of Romanization on the Celtic people of ancient England: benefits, conflicts, influences.
Overview of British dominance of Ireland, Wales, and Scotland! How was this justified in each case, and what motivated the attempts over centuries of rebellion and failure?
Investigate the known consequences of Guttenberg’s printing press within the first 30 years of its invention, and only in regard to the interaction between European nations.
Identify and analyze the point at which the Reformation became fused with European politics and nationalist agendas.
To what extent did Henry VIII promote the Reformation, despite his vigorous persecution of heretics in England?
Trace and discuss the uses of papal power as a military and political device in the 14th and 15th centuries.
Research the city/state of Florence from the 13th to the 16th centuries, discussing how and why it evolved as so fiercely republican.
Compare and contrast the Russian Czarism of Peter, Elizabeth, and Catherine with the monarchies of England and France in the 18th and 19th centuries.
Investigate the enormous significance of Catholic Orthodoxy as the dominant faith in Russia, and its meaning and influence in an empire populated by a minimal aristocracy and predominant serfdom.
To what extent did Philip II’s religious convictions shape European policy and conflict in the 16th century?
Trace the path leading to the convocation of the Estates in France in the late 18th century, leading to the Revolution. Assess political and social errors responsible.
What eventually ended serfdom in Russia, and why were numerous attempts to end it by the Czars in power consistently unsuccessful?
Research and report on how England was transformed in the 19th century by the industrial revolution and the advent of the railroad.
Compare and contrast the consequences of the industrial revolutions in England and America in terms of urbanization.
What were the circumstances leading to World War I, and how might the war have been averted?
Assess the Cold War of the 20th century in an historical context: can any parallels be made between this conflict and other ongoing tensions between major powers in earlier centuries?
Analyze Roosevelt’s decisions in implementing the New Deal, beginning with the closing of the banks. Suggest alternative strategies, or reinforce the rationale of the actions.
What architectural marvels were found in Tenochtitlan, capital of the Aztec Empire?
What was the cultural significance of the first moon landing?
Food programs
Welfare reform
Governmental supplementation
Homeless: urban restrictions vs. needs of the destitute
Workable solutions?
Realistic limits vs. openness toward people in need
English as official language vs. respect for diversity
Should illegal immigrants be made legal citizens?
Access to public school and public programs for Illegal Aliens
Policing borders–workable solutions?
Employment and/or taxation for Illegal Aliens
International trade
Democratization
“Shock and awe”
U.S. occupation vs. liberation
Iraqi run vs. U.S. puppet state
Oil and Gas prices-Control of resources
Effective self-government
War on Terrorism
Is America winning or losing the War? What is the measurement of success? Have the benefits outweighed the costs?
Parental leave for both parents
FMLA (Family Medical Leave Act)
Bonding time
Preemptive strike policy
Precision weapons
Intelligence reliability
Afghanistan – a success or stalemate
Should the U.S. have mandatory military conscriptions? For whom?
Governmental support
Preparedness
School emergency plans
Community warning systems
Damage costs
U.S. presidential elections should be decided by the popular vote, rather than the Electoral College.
The minimum wage should be increased to provide a “livable” wage for working families.
There should be stiffer penalties for those who commit animal cruelty.
School vouchers increase competition and create better quality schools.
The corporate tax rate should be lowered to create more jobs.
Social Security should be privatized.
Human torture should be banned in all circumstances.
Affirmative action is still needed to ensure racial and gender equality.
The U.S. dollar should go back on the gold standard.
Euthanasia and assisted suicide should be outlawed.
Police brutality vs. dangers that police face
Racially motivated brutality?
Politician’s right to privacy vs. the public’s right to know
Amount of money going into presidential campaigns
Views on abortion, gay marriage, and other controversial topics
Political debates throughout history
Third-party candidates at presidential debates
Rights of religious citizens vs. freedom from imposition (e.g. prayer in schools)
Religious motivation for political involvement vs. cultural pluralism
Christian Right’s influence on foreign policy
How serious? Causes? Workable solutions?
Funding abortion as a form of birth control in third world countries?
What would happen globally if the demand for natural resources is greater than the supply?
Limitation of social deterioration vs. freedom of speech
Definition of Pornography
Child Pornography
Building prisons vs. alternative sentencing
Adjusted sentencing for lesser crimes
Community service
Diversion Programs for inmates
How does the prison population in America compare to other nations?
Prostitution laws in the US and abroad
Benefits and drawbacks to legalizing prostitution
Psychological effect on prostitutes and former prostitutes
Sex slavery, buying and selling
Should the government be allowed to wire tap without permission?
What limitations, if any, should be applied to the paparazzi?
What medical information should be confidential? Who, if anybody, should have access to medical records?
Does the public have a right to know about a public figure’s private life?
Privacy rights
Do harsher punishments mean fewer convictions?
Date rape: consent vs. exploitation
Drugs-Rohypnol, GHB, KETAMINE
Legalization of Date Rape Drugs
Recently, a 17-year-old boy was sentenced to 10 years in prison for having consensual oral sex with a 15-year-old girl. Are statutory rape laws patronizing to girls and discriminatory to boys?
Acquaintance rape
Is there one true religion?
Freedom of religion
Offer distinct reasons why the Bible should be studied as literature, removed from religious significance.
From Hollywood to the White House: the political rise of Ronald Reagan.
The Great Communicator: how Reagan captured the hearts of Americans.
1981 assassination attempt: bullet wound leaves Reagan inches away from death.
Reagan appoints the first female Supreme Court justice.
The PATCO breakup and decline of the labor unions.
Tax cuts and “Reaganomics.”
The “Iran-Contra” scandal.
Reagan, Gorbachev, and the end of the Cold War.
The final act: Reagan’s Alzheimer’s disease diagnosis and long goodbye.
How has airport security intensified since September 11th, 2001?
Identity theft
Homeland Security: Are we safer since the creation of this department?
Should the government use invasive pat-downs and body scans to ensure passenger safety or are there better methods?
Is arming Pilots a good idea?
What responsibilities do secret service agents have?
Student loan scams
How to avoid student loan debt
Managing student loan debt
Driverless cars and the future of transportation.
Breaking the glass ceiling: the impact of the women’s rights movement.
How seniors contribute to societal well-being.
How disabled individuals are viewed by society.
The modern-day civil rights movement.
Has technology made us more detached from society?
The role of religion in society.
In today’s society, are we better off or worse off than previous generations?
Popular music and its impact on the culture.
Class and geographical segregation.
The differences between life in the city, suburbs, and/or rural areas.
Should parents be able to create designer babies?
Should microchips be implanted inside humans for better tracking and security?
Will smart watches eventually replace cell phones?
The pros and cons of being a global citizen.
Progressive vs. flat tax
Excessive taxes vs. worthwhile programs
Is text messaging contributing to teen illiteracy?
How eating disorders impact teens.
Tablets vs. textbooks.
Do standardized tests improve teen education?
Are violent video games contributing to juvenile delinquency?
Is English literature relevant for today’s teens?
Should the HPV vaccine be required for teen girls?
Do teachers inflate grades so students can pass?
Should advertisers be allowed to target teens?
How to encourage teens to stop smoking.
The causes and effects of teen alcohol and drug abuse.
How to prevent teen pregnancy.
Osama Bin Laden
World Trade Center and Pentagon bombings
September 11, 2001
War on terrorism
Afghanistan
Bioterrorism
Al Qaida: Has U.S. policy actually spread terrorism rather than contained it? Will it get better or worse? Why and how?
Can terrorism ever be justified?
What kind of person becomes a suicide bomber?
What were the circumstances surrounding the death of Osama Bin Laden?
Has the Patriot Act prevented or stopped terrorist acts in America?
How is text messaging affecting teen literacy?
Cell Phones: How have they changed us socially?
Does the Information Age mean we are losing important historical information?
Where did hip-hop music originate?
A day in the life of a Buddhist monk.
How does the brain store and retrieve memories?
What life is like inside an ant colony.
The case for and against the existence of UFOs.
Can virtual reality adequately substitute for actual reality?
Are dreams hidden messages or just hot air?
Why do people collect the most ridiculous things?
When is it time to get out of an abusive relationship?
The art of pretending to care.
Public attitudes toward veterans
Health issues caused by service time
Organizations for veterans
Governmental support for veterans
What programs are available to help war veterans get back into society?
Iraq War Vets: Are they being cheated on medical benefits?
Is there a glass ceiling?
Obstacles to women running for political office?
Should women be priests, pastors, ministers, and rabbis?
What differences, if any, are there in children who are raised by stay-at-home moms and working moms? Does society today still discriminate against working mothers who wish to have flexible work schedules?
Should stay-at-home moms get a salary from the government?
Why do we sleep?
How do GPS systems work?
Who was the first person to reach the North Pole?
Did anybody ever escape Alcatraz?
What was life like for a gladiator?
Are there any effective means of repelling insects?
How is bulletproof clothing made?
How was the skateboard invented and how has it changed over the years?
What is life like inside of a beehive?
Where did hip hop originate and who were its founders?
What makes the platypus a unique and interesting mammal?
What is daily life like for a Buddhist monk?
How did gunpowder change warfare?
How were cats and dogs domesticated and for what purposes?
What do historians know about ninjas?
Are humans still evolving?
What is the curse of the pharaohs?
Why was Socrates executed?
How did ancient sailors navigate the globe?
How are black holes formed?
How do submarines work?
Do lie detector tests accurately determine truthful statements?
How does a hybrid car save energy?
What ingredients can be found in a hotdog?
How does a shark hunt?
How does the human brain store and retrieve memories?
How does stealth technology shield aircraft from radar?
What causes tornados?
How does night vision work?
What causes desert mirages, and how do they affect wanderers?
What are sinkholes, and how are they formed?
What are the major theories explaining the disappearance of the dinosaurs?
Should we reform laws to make it harder to get a divorce?
Divorce rates
Family relationships
Family values
Race relations
Marriage and Divorce
A view of home life and its effect on child development
How 4 generations in the workplace can work together.
Building positive employee relationships
Modern work environments
Business leadership
Workforce regulations
Small business and taxation
Corporate law
Issues in modern Human Resources: Are today’s corporations patronizing employees or being more responsible for them?
Cultural conflict in globalization: Strategies for successfully establishing a presence in a foreign culture
Corporate abuse: How can executives so successfully manipulate corporations criminally?
Identifying stakeholders in non-public companies: is the corporate responsibility the same as for public offerings?
Devise a new model of leadership for business today, incorporating elements of existing leadership models and theories.
Examine the actual impact of social media as a business promotion instrument.
Devise a scenario in which traditionally unethical business practices may be justified.
Should newspaper reporters be required to reveal their sources?
Do the media (both print and broadcast) report fairly? Do they ever cross the line between reporting the news and creating the news?
Does news coverage favor whites?
What steps are involved in creating a movie or television show?
How have the film and music industries dealt with piracy?
Media conglomerates/ownership
Minorities in mass media
Portrayal of women
Reality television
Television violence
Media portrayals
Sensationalized media
Examine the issues of responsibility in pharmaceutical companies’ promotion of drugs in the media.
Forensic science technology
What are the current capabilities and future goals of genetic engineers?
What obstacles faced scientists in breaking the sound barrier?
What is alchemy and how has it been attempted?
What technologies are available to home owners to help them conserve energy?
Nuclear energy
Clean energy resources
Wind energy: Is wind energy really that inexpensive? Is it effective? Is it practical?
What are the dangers and hazards of using nuclear power?
Investigate Freud’s contributions to psychology as they exist today: what value remains?
Are there gender foundations to psychology and behavior that are removed from cultural considerations? To what extent does gender actually dictate thought process?
To what extent is sexual orientation dictated by culture, and is there an orientation not subject to social and cultural influences?
Investigate the psychological process in group dynamics with regard to the emergence of leaders and the compliance of others.
Compare and contrast Jung, Freud, and Adler: explore distinctions and commonalities.
What is “normal,” and to what extent is psychology reliant on culture to define this?
Research and assess the effectiveness of radical psychotherapies and unconventional treatments.
Research the concept of human will as both a component of individual psychology and a process or element removed from it.
To what extent is self-image influenced by culture in regard to eating disorders? Are external factors entirely to blame?
How do centuries-old beliefs of madness and dementia relate to modern conceptions of mental illness?
Is psychology itself inevitably a non-science in that virtually any theory may be substantiated, or is there a foundation of science to the subject to which all theorists must conform?
Examine Euripides and gender psychology: what do the Trojan Women and Medea reveal?
Using three characters, explore Chaucer’s insight into human behavior in The Canterbury Tales.
Identify the true relationship between Dante and Virgil in The Divine Comedy, emphasizing Dante’s reliance on the poet.
Research and discuss the English fascination for euphemism and ornate narratives in the 16th century, beginning with John Lyly.
Examine any existing controversies regarding Shakespearean authorship, citing arguments on both sides.
Analyze similarities and differences between Marlowe and Shakespeare in regard to Tamburlaine and Titus Andronicus.
Defend or support Bloom’s assertion of Shakespeare as the “inventor of the human being.”
To what degree are Shakespeare’s plays influenced by, or reflective, of the Elizabethan era? Identify specific cultural and national events linked to at least 3 plays.
Analyze the unusual construction of A Winter’s Tale in regard to transition from comedy to drama. Is this valid? Does the transition benefit or harm the play?
Support the belief that Shakespeare is representing himself as Prospero through evidence, or similarly refute the belief.
Why was extreme violence so popular in English Reformation drama? Cite Marlowe, Kyd, Webster, and Shakespeare.
Analyze the metaphysical in Donne’s poetry: is it spiritual, existential, or both?
What is Shelley seeking to say in Frankenstein? Support your answer with passages from the novel.
Compare and contrast Tolstoy’s Anna Karenina with Flaubert’s Madame Bovary, noting the characters of the heroines.
It is argued that Dickens failed when he turned to serious, romantic narrative in his novels. Using Copperfield, Great Expectations, and Dombey and Son, defend or refute this claim.
Assess Dickens’ stance as a moralist in Bleak House and Hard Times: to what extent does he seek reform, and to what does he comment on the human condition?
Was the Harry Potter phenomenon warranted by quality of storytelling or more a matter of public receptivity at the time combined with media exposure?

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20 thoughts on “717 Good Research Paper Topics”

How has music evolved? How has music effected history? Music of the past vs music of the present. How has the music industry effected the music’s quality?

Do you think abortion is legal? Why they do abortion?

Why are people instinctively afraid of animals that are not mammals?

Should abortion be legalized? Should domestic abuse and child abuse victims be granted clemency for killing their abuser?

Jewish holocaust and its contribution to European History, specifically Germany

What is the most popular college in the United States?

The Black Knight: Space Waste or Alien Satellite? The Moon Landing: Real or Hollywood Hoax? Have We Become Too Politically Correct? Paranormal Research: Real? Fake? Should it be offered in college? Who really was Jack the Ripper? Can a zombie apocalypse truly occur? Who is the best or worst president of the USA? The Men in Black: real or hoax?

Why Marching Band is a sport.

Marching band is not a sport

how did aids start?

Topic : Alternative medicine Research question : Does the alternative medicine is safe and standardized Hypothesis : analyse the quality controle of alternative medicine formulations

Does our nostalgic music/childhood songs affect our present lifestyle, and in what ways?

reverse discriminations is still discrimination so there’s no such thing as that. like reverse racism isn’t a thing because that is still racism

Men on birth control and not women.

You forget the topic Islamophobia 😉

You should add a music section. Is Muzio Clementi overshadowed by Mozart? The Toccata and Fugue in D- really wasn’t written by Bach The use of the “Dies Irae” in cinema Why is modern music so repetitive and simple compared to classical music?

I want to do a research project on Education

I want to research but not get a perfect topic help me give me a best topic about current affairs

Topic: History. Are the Crusades oversimplified? where they justified? If so, how? Topic: Current affairs. Is the term “conspiracy theory” used to discredit any non-mainstream, controversial opinions. Topic: Gun control. Does limiting magazine capacity for firearms have any effect on gun crime? Are high-capacity magazines ever necessary for self-defense? Topic: Economics. Are minimum wage laws necessary to guarantee “decent”, or do the laws of supply and demand automatically ensure that?

Are women funny?

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Research Paper Topics for 2024: Explore Ideas Across Various Fields

When you start writing a research paper, it’s like diving into a big pool of exploration and analysis. A good research paper goes beyond just gathering facts. It’s more about exploring a topic, asking the right questions, and coming up with thoughtful answers. Whether you're looking at historical events, scientific discoveries, or cultural trends, the trick is to find interesting research topics that catch your interest and keep you motivated throughout the process.

This article is here to help with that sometimes tricky job of picking a topic. We’ll cover a variety of interesting research topics from different areas, making it easier for you to find one that not only fits your assignment but also grabs your attention.

But let’s be honest, picking the right topic isn’t always easy. If you’re still unsure after reading this article, EssayService is a great place to turn for help, whether you need assistance choosing a topic or writing the entire paper.

How to Pick a Topic for a Research Paper

Choosing the right topic can make or break your research paper. Here's how to make it easier:

Start with your interests: Pick a few areas or subjects that genuinely interest you. Narrow it down to the one that excites you the most. If you’re interested, it’ll show in your writing.
Check for resources: Before committing, do a quick search to ensure there are enough references available. You’ll want a topic that’s well-discussed so you have plenty of material to work with.
Stick to guidelines: Make sure your topic fits within any guidelines your teacher has set. Whether it's avoiding certain subjects or meeting specific requirements, this step is crucial for getting your paper off to a good start.

If you’re looking for easy research paper topics, keep these tips in mind to ensure you choose one that’s both manageable and engaging.

What Are Good Research Topics?

Choosing a successful research topic isn’t just about what sounds interesting — it’s about finding a topic that will help you produce a strong, insightful paper. Good research topic ideas should tick a few key boxes to ensure they’re both impactful and manageable.

Feature	Description
🔍 Specific and Focused	Narrow down broad areas like “climate change” to something more specific, like “the impact of urban development on local microclimates.” This gives your research a clear direction.
✨ Unique Angle	Instead of rehashing well-covered topics like “social media and mental health,” explore a niche, such as “the effects of social media detox on productivity in college students.”
🌍 Significant Impact	Choose topics that matter, like “renewable energy adoption in developing countries,” which could contribute to important discussions in your field or society.
📚 Accessible Sources	Make sure there’s enough material available by checking databases for studies on topics like “the history of vaccine development” to ensure you have the resources you need.
🔥 Current and Relevant	Focus on emerging issues, such as “the role of AI in cybersecurity,” which are timely and likely to interest both readers and reviewers.

Best Research Paper Topics for 2024

In 2024, new challenges and innovations are shaping the world around us, making it an exciting time to dive into research. Here are 15 detailed and highly relevant topics that will keep your paper ahead of the curve:

The impact of remote work on urban development in major U.S. cities.
Ethical implications of AI-driven decision-making in healthcare.
The role of social media algorithms in shaping public opinion during elections.
Effects of climate change on global food security and crop yields.
The influence of blockchain technology on supply chain transparency.
Mental health outcomes related to long-term social media use among teenagers.
Renewable energy adoption in emerging economies and its impact on local communities.
The rise of electric vehicles and its effect on traditional automotive industries.
Privacy concerns surrounding the use of biometric data in consumer devices.
The evolution of cybersecurity threats in the age of quantum computing.
Gender disparities in STEM education and their long-term effects on the workforce.
The economic impact of climate migration on coastal regions.
Implications of CRISPR technology in human genetic modification.
The effectiveness of universal basic income trials in reducing poverty.
The role of telemedicine in improving access to healthcare in rural areas.

College Research Paper Topics

These topics explore some of the most relevant and intriguing issues facing college students today, offering plenty of angles to explore in your research:

How student loan debt shapes career paths and financial stability after graduation.
Comparing online learning to traditional classrooms: What works best for today’s college students?
Social media’s influence on mental health and academic success among college students.
Diversity and inclusion: How initiatives are changing campus life and student experiences.
University sustainability efforts: How climate change is driving new campus policies.
The rise of esports: Transforming college athletics and student engagement.
Campus housing: How living arrangements affect academic success and student retention.
Balancing part-time jobs with academics: The impact on college students’ grades and well-being.
Navigating controversial topics: The importance of academic freedom in college debates.
Digital vs. traditional libraries: How technology is reshaping student research habits.
Study abroad programs: Enhancing global awareness and boosting future career opportunities.
Evaluating campus mental health services: Are they meeting students’ needs?
Fraternities and sororities: Examining their influence on college culture and student life.
Free college tuition: Exploring the economic and social outcomes in different countries.
Standardized testing: How it’s affecting college admissions and the diversity of student bodies.

Research Paper Topics By Subject

Choosing a good research topic that aligns with your academic focus can make your work more relevant and engaging. Below, you’ll find topics organized by subject to help you get started.

Research Paper Topics on Health

Health is a dynamic field with ongoing developments and challenges, making it a rich area for research. These topics cover a range of health-related issues, from public health policies to advancements in medical technology:

How COVID-19 has changed the approach to mental health care.
Adoption rates of telemedicine among different age groups.
Antibiotic-resistant bacteria: Exploring new treatment options.
Barriers to healthcare access in low-income neighborhoods.
Ethical dilemmas in using genetic testing for personalized treatments.
Success rates of mental health programs in high schools.
Comparing dietary patterns in managing type 2 diabetes across cultures.
Teen vaping trends and their connection to lung health issues.
Strategies for supporting healthcare needs in rapidly aging populations.
Tracking climate-related health issues in coastal communities.
Innovations in vaccine development for emerging diseases.
Social isolation during pandemics and its link to anxiety disorders.
Recent changes in U.S. healthcare laws and their influence on patient choices.
Exploring how traditional beliefs shape approaches to medical treatment.
Evaluating progress in global vaccination campaigns against childhood diseases.

Research Paper Topics on Medicine

Medicine is a vast field with plenty of areas to explore. Here are some specific topics that focus on medical advancements, practices, and challenges:

New techniques in minimally invasive surgery for heart conditions.
Developments in gene therapy for treating inherited diseases.
Challenges in diagnosing and treating rare diseases.
The role of AI in improving diagnostic accuracy in radiology.
Progress in personalized cancer treatments based on genetic profiling.
The rise of antibiotic alternatives in treating infections.
Stem cell research advancements for spinal cord injuries.
Managing chronic pain: Exploring non-opioid treatment options.
Trends in telemedicine for rural healthcare delivery.
Breakthroughs in vaccine technology for emerging viruses.
Long-term outcomes of organ transplants in pediatric patients.
Advances in robotic surgery and their impact on patient recovery.
New approaches to treating drug-resistant tuberculosis.
Innovations in prenatal care and fetal surgery techniques.
The future of regenerative medicine and tissue engineering.

Research Paper Topics on Media

Explore the ever-changing world of media with these fresh and relevant topics. Each one dives into the trends and challenges shaping how we consume and create content today.

Analyze the impact of TikTok on modern marketing strategies.
Investigate the role of influencers in shaping public opinion during elections.
Explore the effects of streaming services on traditional cable TV viewership.
Examine how social media platforms handle misinformation and its consequences.
Study the rise of podcasts and their influence on news consumption.
Compare the portrayal of mental health in TV shows across different cultures.
Track the evolution of digital journalism and its impact on print media.
Look into the ethics of deepfake technology in video production.
Research the effects of binge-watching on viewer behavior and mental health.
Explore the relationship between video game streaming and the gaming industry.
Analyze the shift from traditional news outlets to social media for breaking news.
Investigate how algorithms curate personalized content and influence user behavior.
Study the changing landscape of advertising in the age of ad-blockers.
Examine the role of memes in political discourse and cultural commentary.
Explore the use of virtual reality in media and entertainment.

Research Paper Topics on Politics

Politics is a field that’s constantly evolving, with new issues and debates emerging all the time. Whether you're interested in global dynamics, domestic policies, or the role of technology in politics, there’s no shortage of interesting topics to explore:

How social media is influencing voter behavior in recent elections.
The rise and impact of grassroots movements on political change.
Fake news and its role in shaping public perception of political events.
The effects of immigration policies on relationships between countries.
Populism’s growth in global politics and what it means for the future.
How economic inequality contributes to political instability.
The power of political lobbying in creating and shaping laws.
Challenges faced by democracies under authoritarian regimes.
Youth activism and its growing influence in modern politics.
How climate change policies are impacting national security.
The role of technology in improving election security and voter turnout.
Government approval ratings and their connection to pandemic responses.
Influence of international organizations on a country’s domestic policies.
Shifts in global trade agreements and their effects on international relations.
The impact of gerrymandering on election results and fairness.

Research Paper Ideas on Technology

Technology is rapidly transforming our world, offering endless opportunities for research. Here are some intriguing ideas to explore:

The ethics of artificial intelligence in decision-making processes.
How blockchain technology is revolutionizing financial transactions.
The role of 5G networks in shaping the future of communication.
Cybersecurity challenges in the era of smart homes and IoT devices.
The environmental impact of cryptocurrency mining.
Virtual reality’s influence on education and training programs.
How autonomous vehicles are changing urban planning and infrastructure.
The potential of quantum computing in solving complex global problems.
Social media algorithms and their impact on public discourse.
The digital divide: Access to technology in rural versus urban areas.
How wearable tech is transforming personal health management.
The implications of deepfake technology in media and politics.
The future of remote work and its long-term effects on productivity.
Advancements in drone technology for disaster management and rescue operations.
The role of big data in personalizing online shopping experiences.

Research Topic Ideas on Culture

Whether you’re interested in examining specific cultural practices or looking at how modern trends reshape traditional customs, these research topics will provide you with a focused and detailed starting point:

Adoption of traditional Japanese tea ceremonies in contemporary urban settings.
Practices of food preservation among Inuit communities in the Arctic.
The revival of Celtic languages in Wales and Ireland through education programs.
Depiction of queer relationships in Netflix original series from 2015 to 2024.
Evolution of traditional African hairstyles in Black communities across the U.S.
Transformation of street art in Berlin post-German reunification.
Cultural significance of Día de los Muertos celebrations in Mexican-American neighborhoods.
Popularity of Korean skincare routines among Western beauty bloggers.
Modern interpretations of Norse mythology in Scandinavian literature.
Changes in wedding rituals among Indian diaspora in the UK.
Resurgence of indigenous Australian painting techniques in contemporary art.
Representation of disability in children’s books published in the last decade.
Use of traditional Māori patterns in New Zealand’s fashion industry.
Changes in burial customs in urbanized areas of Southeast Asia.
Incorporation of First Nations symbols in Canadian public architecture.

Research Paper Topics on Math

If you're looking to explore the depth and applications of math, these research topics are both specific and engaging:

Applications of fractal geometry in modeling natural phenomena.
Mathematical approaches to solving complex optimization problems in logistics.
Development of new algorithms for large-scale data encryption.
Mathematical modeling of population dynamics in ecology.
The use of game theory in economic decision-making processes.
Exploring the mathematics behind machine learning algorithms.
Advancements in numerical methods for solving partial differential equations.
Topological data analysis and its applications in computational biology.
Mathematical analysis of voting systems and fairness.
The role of number theory in modern cryptography.
Predictive models for financial markets using stochastic calculus.
Mathematical foundations of quantum computing and quantum algorithms.
Applications of chaos theory in weather prediction.
Geometry of space-time in the context of general relativity.
Mathematical techniques for analyzing big data in social networks.

Research Paper Topics on Art

Art is full of fascinating details and stories waiting to be explored. If you’re into art research, here are some research topics that might catch your interest:

How Caravaggio used light and shadow in his religious paintings.
The way Cubism shaped Picasso’s "Les Demoiselles d’Avignon."
Gustav Klimt’s "The Kiss" and its ties to Viennese culture.
Hokusai’s woodblock techniques in "The Great Wave off Kanagawa."
Bauhaus principles that still influence graphic design today.
Emotions and color in Mark Rothko’s abstract paintings.
Leonora Carrington’s role in the Surrealist movement.
Gaudí’s architectural genius in designing La Sagrada Familia.
Industrial scenes captured in Charles Sheeler’s Precisionist art.
Jean-Michel Basquiat’s take on graffiti and cultural identity.
Frida Kahlo’s evolving self-portraits through her life.
Claude Monet’s unique use of light in his Impressionist works.
Diego Rivera’s murals as powerful political statements.
The simplicity and impact of Donald Judd’s minimalist sculptures.
How African art influenced Henri Matisse during his Fauvist period.

Research Topics on Sports

Sports offer a wide range of topics that are both intriguing and highly relevant. Here are some specific research ideas to consider if you're looking to explore the world of sports:

The biomechanics behind sprinting techniques in elite athletes.
The psychological effects of team sports on adolescent development.
Injury prevention strategies in professional football (soccer).
The impact of altitude training on endurance performance in marathon runners.
Gender equity in sports: The evolution of women’s participation in the Olympics.
The role of nutrition in recovery and performance for endurance athletes.
How advanced analytics are changing strategies in basketball.
The effects of early specialization in youth sports on long-term athletic development.
The influence of sports media coverage on public perceptions of athletes.
Technology in sports: The use of wearable devices to monitor athlete performance.
Doping scandals and their long-term impact on athletes' careers.
Mental health challenges faced by retired professional athletes.
The economics of hosting major sporting events like the World Cup or Olympics.
How climate change is affecting outdoor sports events and training schedules.
The evolution of sports science in enhancing athlete training programs.

In 2024, some of the most popular research topics include the impact of technology on sports, the psychological aspects of team dynamics, and the evolution of gender equity in athletics.

If you’re still unsure about which topic to choose or need help with your essay, EssayService is a great option. Our research paper writing service can assist with everything from selecting the perfect topic to crafting a well-written paper, making the whole process a lot easier.

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Starting the research process

How to Choose a Dissertation Topic | 8 Steps to Follow

Published on November 11, 2022 by Shona McCombes and Tegan George. Revised on November 20, 2023.

Choosing your dissertation topic is the first step in making sure your research goes as smoothly as possible. When choosing a topic, it’s important to consider:

Your institution and department’s requirements
Your areas of knowledge and interest
The scientific, social, or practical relevance
The availability of data and resources
The timeframe of your dissertation
The relevance of your topic

You can follow these steps to begin narrowing down your ideas.

Step 1: check the requirements, step 2: choose a broad field of research, step 3: look for books and articles, step 4: find a niche, step 5: consider the type of research, step 6: determine the relevance, step 7: make sure it’s plausible, step 8: get your topic approved, other interesting articles, frequently asked questions about dissertation topics.

The very first step is to check your program’s requirements. This determines the scope of what it is possible for you to research.

Is there a minimum and maximum word count?
When is the deadline?
Should the research have an academic or a professional orientation?
Are there any methodological conditions? Do you have to conduct fieldwork, or use specific types of sources?

Some programs have stricter requirements than others. You might be given nothing more than a word count and a deadline, or you might have a restricted list of topics and approaches to choose from. If in doubt about what is expected of you, always ask your supervisor or department coordinator.

Start by thinking about your areas of interest within the subject you’re studying. Examples of broad ideas include:

Twentieth-century literature
Economic history
Health policy

To get a more specific sense of the current state of research on your potential topic, skim through a few recent issues of the top journals in your field. Be sure to check out their most-cited articles in particular. For inspiration, you can also search Google Scholar , subject-specific databases , and your university library’s resources.

As you read, note down any specific ideas that interest you and make a shortlist of possible topics. If you’ve written other papers, such as a 3rd-year paper or a conference paper, consider how those topics can be broadened into a dissertation.

After doing some initial reading, it’s time to start narrowing down options for your potential topic. This can be a gradual process, and should get more and more specific as you go. For example, from the ideas above, you might narrow it down like this:

Twentieth-century literature Twentieth-century Irish literature Post-war Irish poetry
Economic history European economic history German labor union history
Health policy Reproductive health policy Reproductive rights in South America

All of these topics are still broad enough that you’ll find a huge amount of books and articles about them. Try to find a specific niche where you can make your mark, such as: something not many people have researched yet, a question that’s still being debated, or a very current practical issue.

At this stage, make sure you have a few backup ideas — there’s still time to change your focus. If your topic doesn’t make it through the next few steps, you can try a different one. Later, you will narrow your focus down even more in your problem statement and research questions .

There are many different types of research , so at this stage, it’s a good idea to start thinking about what kind of approach you’ll take to your topic. Will you mainly focus on:

Collecting original data (e.g., experimental or field research)?
Analyzing existing data (e.g., national statistics, public records, or archives)?
Interpreting cultural objects (e.g., novels, films, or paintings)?
Comparing scholarly approaches (e.g., theories, methods, or interpretations)?

Many dissertations will combine more than one of these. Sometimes the type of research is obvious: if your topic is post-war Irish poetry, you will probably mainly be interpreting poems. But in other cases, there are several possible approaches. If your topic is reproductive rights in South America, you could analyze public policy documents and media coverage, or you could gather original data through interviews and surveys .

You don’t have to finalize your research design and methods yet, but the type of research will influence which aspects of the topic it’s possible to address, so it’s wise to consider this as you narrow down your ideas.

It’s important that your topic is interesting to you, but you’ll also have to make sure it’s academically, socially or practically relevant to your field.

Academic relevance means that the research can fill a gap in knowledge or contribute to a scholarly debate in your field.
Social relevance means that the research can advance our understanding of society and inform social change.
Practical relevance means that the research can be applied to solve concrete problems or improve real-life processes.

The easiest way to make sure your research is relevant is to choose a topic that is clearly connected to current issues or debates, either in society at large or in your academic discipline. The relevance must be clearly stated when you define your research problem .

Before you make a final decision on your topic, consider again the length of your dissertation, the timeframe in which you have to complete it, and the practicalities of conducting the research.

Will you have enough time to read all the most important academic literature on this topic? If there’s too much information to tackle, consider narrowing your focus even more.

Will you be able to find enough sources or gather enough data to fulfil the requirements of the dissertation? If you think you might struggle to find information, consider broadening or shifting your focus.

Do you have to go to a specific location to gather data on the topic? Make sure that you have enough funding and practical access.

Last but not least, will the topic hold your interest for the length of the research process? To stay motivated, it’s important to choose something you’re enthusiastic about!

Most programmes will require you to submit a brief description of your topic, called a research prospectus or proposal .

Remember, if you discover that your topic is not as strong as you thought it was, it’s usually acceptable to change your mind and switch focus early in the dissertation process. Just make sure you have enough time to start on a new topic, and always check with your supervisor or department.

If you want to know more about the research process , methodology , research bias , or statistics , make sure to check out some of our other articles with explanations and examples.

Methodology

Sampling methods
Simple random sampling
Stratified sampling
Cluster sampling
Likert scales
Reproducibility

Statistics

Null hypothesis
Statistical power
Probability distribution
Effect size
Poisson distribution

Research bias

Optimism bias
Cognitive bias
Implicit bias
Hawthorne effect
Anchoring bias
Explicit bias

Formulating a main research question can be a difficult task. Overall, your question should contribute to solving the problem that you have defined in your problem statement .

However, it should also fulfill criteria in three main areas:

Researchability
Feasibility and specificity
Relevance and originality

All research questions should be:

Focused on a single problem or issue
Researchable using primary and/or secondary sources
Feasible to answer within the timeframe and practical constraints
Specific enough to answer thoroughly
Complex enough to develop the answer over the space of a paper or thesis
Relevant to your field of study and/or society more broadly

You can assess information and arguments critically by asking certain questions about the source. You can use the CRAAP test , focusing on the currency , relevance , authority , accuracy , and purpose of a source of information.

Ask questions such as:

Who is the author? Are they an expert?
Why did the author publish it? What is their motivation?
How do they make their argument? Is it backed up by evidence?

A dissertation prospectus or proposal describes what or who you plan to research for your dissertation. It delves into why, when, where, and how you will do your research, as well as helps you choose a type of research to pursue. You should also determine whether you plan to pursue qualitative or quantitative methods and what your research design will look like.

It should outline all of the decisions you have taken about your project, from your dissertation topic to your hypotheses and research objectives , ready to be approved by your supervisor or committee.

Note that some departments require a defense component, where you present your prospectus to your committee orally.

The best way to remember the difference between a research plan and a research proposal is that they have fundamentally different audiences. A research plan helps you, the researcher, organize your thoughts. On the other hand, a dissertation proposal or research proposal aims to convince others (e.g., a supervisor, a funding body, or a dissertation committee) that your research topic is relevant and worthy of being conducted.

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McCombes, S. & George, T. (2023, November 20). How to Choose a Dissertation Topic | 8 Steps to Follow. Scribbr. Retrieved August 29, 2024, from https://www.scribbr.com/research-process/dissertation-topic/

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61 intriguing psychology research topics to explore

Last updated

11 January 2024

Reviewed by

Brittany Ferri, PhD, OTR/L

Short on time? Get an AI generated summary of this article instead

Psychology is an incredibly diverse, critical, and ever-changing area of study in the medical and health industries. Because of this, it’s a common area of study for students and healthcare professionals.

We’re walking you through picking the perfect topic for your upcoming paper or study. Keep reading for plenty of example topics to pique your interest and curiosity.

How to choose a psychology research topic

Exploring a psychology-based topic for your research project? You need to pick a specific area of interest to collect compelling data.

Use these tips to help you narrow down which psychology topics to research:

Focus on a particular area of psychology

The most effective psychological research focuses on a smaller, niche concept or disorder within the scope of a study.

Psychology is a broad and fascinating area of science, including everything from diagnosed mental health disorders to sports performance mindset assessments.

This gives you plenty of different avenues to explore. Having a hard time choosing? Check out our list of 61 ideas further down in this article to get started.

Read the latest clinical studies

Once you’ve picked a more niche topic to explore, you need to do your due diligence and explore other research projects on the same topic.

This practice will help you learn more about your chosen topic, ask more specific questions, and avoid covering existing projects.

For the best results, we recommend creating a research folder of associated published papers to reference throughout your project. This makes it much easier to cite direct references and find inspiration down the line.

Find a topic you enjoy and ask questions

Once you’ve spent time researching and collecting references for your study, you finally get to explore.

Whether this research project is for work, school, or just for fun, having a passion for your research will make the project much more enjoyable. (Trust us, there will be times when that is the only thing that keeps you going.)

Now you’ve decided on the topic, ask more nuanced questions you might want to explore.

If you can, pick the direction that interests you the most to make the research process much more enjoyable.

61 psychology topics to research in 2024

Need some extra help starting your psychology research project on the right foot? Explore our list of 61 cutting-edge, in-demand psychology research topics to use as a starting point for your research journey.

Psychology research topics for university students

As a university student, it can be hard to pick a research topic that fits the scope of your classes and is still compelling and unique.

Here are a few exciting topics we recommend exploring for your next assigned research project:

Mental health in post-secondary students

Seeking post-secondary education is a stressful and overwhelming experience for most students, making this topic a great choice to explore for your in-class research paper.

Examples of post-secondary mental health research topics include:

Student mental health status during exam season

Mental health disorder prevalence based on study major

The impact of chronic school stress on overall quality of life

The impacts of cyberbullying

Cyberbullying can occur at all ages, starting as early as elementary school and carrying through into professional workplaces.

Examples of cyberbullying-based research topics you can study include:

The impact of cyberbullying on self-esteem

Common reasons people engage in cyberbullying

Cyberbullying themes and commonly used terms

Cyberbullying habits in children vs. adults

The long-term effects of cyberbullying

Clinical psychology research topics

If you’re looking to take a more clinical approach to your next project, here are a few topics that involve direct patient assessment for you to consider:

Chronic pain and mental health

Living with chronic pain dramatically impacts every aspect of a person’s life, including their mental and emotional health.

Here are a few examples of in-demand pain-related psychology research topics:

The connection between diabetic neuropathy and depression

Neurological pain and its connection to mental health disorders

Efficacy of meditation and mindfulness for pain management

The long-term effects of insomnia

Insomnia is where you have difficulty falling or staying asleep. It’s a common health concern that impacts millions of people worldwide.

This is an excellent topic because insomnia can have a variety of causes, offering many research possibilities.

Here are a few compelling psychology research topics about insomnia you could investigate:

The prevalence of insomnia based on age, gender, and ethnicity

Insomnia and its impact on workplace productivity

The connection between insomnia and mental health disorders

Efficacy and use of melatonin supplements for insomnia

The risks and benefits of prescription insomnia medications

Lifestyle options for managing insomnia symptoms

The efficacy of mental health treatment options

Management and treatment of mental health conditions is an ever-changing area of study. If you can witness or participate in mental health therapies, this can make a great research project.

Examples of mental health treatment-related psychology research topics include:

The efficacy of cognitive behavioral therapy (CBT) for patients with severe anxiety

The benefits and drawbacks of group vs. individual therapy sessions

Music therapy for mental health disorders

Electroconvulsive therapy (ECT) for patients with depression

Controversial psychology research paper topics

If you are looking to explore a more cutting-edge or modern psychology topic, you can delve into a variety of controversial and topical options:

The impact of social media and digital platforms

Ever since access to internet forums and video games became more commonplace, there’s been growing concern about the impact these digital platforms have on mental health.

Examples of social media and video game-related psychology research topics include:

The effect of edited images on self-confidence

How social media platforms impact social behavior

Video games and their impact on teenage anger and violence

Digital communication and the rapid spread of misinformation

The development of digital friendships

Psychotropic medications for mental health

In recent years, the interest in using psychoactive medications to treat and manage health conditions has increased despite their inherently controversial nature.

Examples of psychotropic medication-related research topics include:

The risks and benefits of using psilocybin mushrooms for managing anxiety

The impact of marijuana on early-onset psychosis

Childhood marijuana use and related prevalence of mental health conditions

Ketamine and its use for complex PTSD (C-PTSD) symptom management

The effect of long-term psychedelic use and mental health conditions

Mental health disorder research topics

As one of the most popular subsections of psychology, studying mental health disorders and how they impact quality of life is an essential and impactful area of research.

While studies in these areas are common, there’s always room for additional exploration, including the following hot-button topics:

Anxiety and depression disorders

Anxiety and depression are well-known and heavily researched mental health disorders.

Despite this, we still don’t know many things about these conditions, making them great candidates for psychology research projects:

Social anxiety and its connection to chronic loneliness

C-PTSD symptoms and causes

The development of phobias

Obsessive-compulsive disorder (OCD) behaviors and symptoms

Depression triggers and causes

Self-care tools and resources for depression

The prevalence of anxiety and depression in particular age groups or geographic areas

Bipolar disorder

Bipolar disorder is a complex and multi-faceted area of psychology research.

Use your research skills to learn more about this condition and its impact by choosing any of the following topics:

Early signs of bipolar disorder

The incidence of bipolar disorder in young adults

The efficacy of existing bipolar treatment options

Bipolar medication side effects

Cognitive behavioral therapy for people with bipolar

Schizoaffective disorder

Schizoaffective disorder is often stigmatized, and less common mental health disorders are a hotbed for new and exciting research.

Here are a few examples of interesting research topics related to this mental health disorder:

The prevalence of schizoaffective disorder by certain age groups or geographic locations

Risk factors for developing schizoaffective disorder

The prevalence and content of auditory and visual hallucinations

Alternative therapies for schizoaffective disorder

Societal and systematic psychology research topics

Modern society’s impact is deeply enmeshed in our mental and emotional health on a personal and community level.

Here are a few examples of societal and systemic psychology research topics to explore in more detail:

Access to mental health services

While mental health awareness has risen over the past few decades, access to quality mental health treatment and resources is still not equitable.

This can significantly impact the severity of a person’s mental health symptoms, which can result in worse health outcomes if left untreated.

Explore this crucial issue and provide information about the need for improved mental health resource access by studying any of the following topics:

Rural vs. urban access to mental health resources

Access to crisis lines by location

Wait times for emergency mental health services

Inequities in mental health access based on income and location

Insurance coverage for mental health services

Systemic racism and mental health

Societal systems and the prevalence of systemic racism heavily impact every aspect of a person’s overall health.

Researching these topics draws attention to existing problems and contributes valuable insights into ways to improve access to care moving forward.

Examples of systemic racism-related psychology research topics include:

Access to mental health resources based on race

The prevalence of BIPOC mental health therapists in a chosen area

The impact of systemic racism on mental health and self-worth

Racism training for mental health workers

The prevalence of mental health disorders in discriminated groups

LGBTQIA+ mental health concerns

Research about LGBTQIA+ people and their mental health needs is a unique area of study to explore for your next research project. It’s a commonly overlooked and underserved community.

Examples of LGBTQIA+ psychology research topics to consider include:

Mental health supports for queer teens and children

The impact of queer safe spaces on mental health

The prevalence of mental health disorders in the LGBTQIA+ community

The benefits of queer mentorship and found family

Substance misuse in LQBTQIA+ youth and adults

Collect data and identify trends with Dovetail

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Take the headache out of analyzing your data and instantly access the insights you need to complete your next psychology research project by teaming up with Dovetail today.

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Robert W. Woodruff Library

Q. How can I choose a good topic for my research paper?

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Answered By: Woodruff Library Reference Last Updated: Mar 12, 2024 Views: 603508

How do you decide what to write about when confronted with a research paper? You want a focused topic!

Here are some things to consider:

Make sure your topic meets the assignment requirements. Ask your professor for feedback if you are unsure.
Choose a topic that is interesting to you. It may seem obvious, but this will make the research process more fun and engaging for you.
Consider the scope of your topic. If your topic is too broad it may be hard to find information that is focused and relevant; if your topic is too narrow it may be hard to find any information at all.

Here's one strategy for developing a research topic once you have a broad topic in mind:

Background research will help you develop your topic and hone or change it in more appropriate ways. Knowing more about your topic's background can only help you develop a more effective topic, and therefore, research paper.
Brainstorm concepts. Once you think of a broad topic that interests you, try to brainstorm all of the words or concepts you can that might be related to that topic (and write them down!). For example, if your topic is "polar bears," you might think of the following words and topics in association: ice, cubs, pollution, hunting, diet, climate change, and environmental icon.
Develop a research question . Once you have come up with a broad topic and done some background research, you may want to develop a research question, or a question you're going to answer in your paper by doing more, in-depth research.
What's your general approach to the topic? Think about some general approaches that may help you further develop your topic: use a historical angle by focusing on a particular time period; a geographical angle, focusing on a particular part of the world; or a sociological angle, focusing on a particular group of people.
Start doing some exploratory, in-depth research. As you do more in-depth research, like looking for scholarly articles, books, and other sources to include in your paper, you can and probably will modify or refine your topic based on what you find.
Research is a dynamic process. Don't be afraid to discover new things and modify or refine your topic.

The topic development process will help you to develop your thesis , which is essentially your proposed answer to your research question. You will then be ready to use the sources you've found, and find more sources in order to support that thesis, or to answer your research question.

Here's an example of how the topic development process above can lead you to a thesis:

Resources that can help you develop your topic:

Your instructor, course readings, class notes, Wikipedia, and Google can all be helpful in terms of getting ideas for broad topics.
A Research Guide for a particular subject created by a subject librarian is great for helping you choose where to begin your research. These online guides will identify encyclopedias, books, databases, and other materials to help you get started with research. You can also ask a librarian at the Library Service Desk.
Library resources like Credo Reference Unlimited , Gale Virtual Reference Library , CQ Researcher and subject-specific encyclopedias can help you come up with topic ideas because they provide great overviews and introductions to topics. You can find links to these kinds of resources in the Research Guides mentioned above. These will probably not be scholarly sources you can use in your paper, but they may lead you to more in-depth, scholarly resources that you will want to use in your paper.

Check out this video from NCSU Libraries:

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Speaker 1: One of the most frequently asked questions that I am asked all the time across my social media platforms, across my YouTube, across my comments, is about the research process. So how do you start? Where do you even begin? You need to submit a dissertation, you need to submit a research proposal, you need to think of a hypothesis, you need to think of a problem statement, you need to find a gap in literature where do you even begin with the whole research process now it isn't as hard as it seems it's just one of those things that you're never told or you're never taught how to do it's one of those things that you just kind of figure out so hopefully in today's video i will be talking to you about the overview and kind of a quick beginner's guide to the research process, giving you the steps of how you get from zero to having something, having a question, having a hypothesis, having somewhere to start. I'm going to be making this into a bit of a series so in today's video I'm going to be giving you an overview as to the different chapters, the different sections of the process, how you get from nothing to something and then in the following videos I will be going through each of those sections in a bit more detail and hopefully if you are someone who is within one of those kind of parts you can just jump to that video and have a have a quick quick watch if you are someone who is just starting off then this is the best place for you to begin have a little think about how you're going to navigate your research process and how you're going to get from the start to the end it is not difficult but it does require a few steps, a few technicalities, which I'll talk you through today. I'll leave the timestamps down below so you feel free to go and jump to the different sections that you are interested in watching. And if you do enjoy this kind of video and you want to see the rest of the videos from me, then don't forget to subscribe to see more on my channel. So step number one is to choose a topic. Now this is the beginning of something beautiful. This is where you choose what you're actually going to be studying and when you're actually going to be reading about now it's really important that you have chosen a topic that you are interested in that there is an interest in within the research space that has something missing so you don't want to choose a topic that we know everything about you want to choose a topic that we don't know everything about and there are things that we want to try to find more about you want to choose a topic that is within your university guidelines so as much as i would love to do a research on the solar system about space well if my course is to do with cell biology well then i can't so you have to think about your limits think about what you are allowed to do within your university guidelines as well but you do need to think about taking that broad topic and making it into something a bit more narrow so it's not good enough to just say i want to do research on alzheimer's okay alzheimer's fine you've got a topic, but you now need to narrow it down. So what about it are you looking at? Are you looking at the risk factors? Are you looking at what happens once you have Alzheimer's? Are you looking at a specific group of people? Are you looking at a specific cell type? What is it that you are looking at? You need to narrow that down. In order to narrow it down, you need to do a bit of a literature search. So whilst choosing a topic, whilst in this first stage, you need to look at literature. So to find literature you want to go to different websites where you have literature and this could be for example Google Scholar is a good place to start, PubMed is a good place to start. These are places where you can find literature about that topic and kind of read around the subject and identify whether firstly is it something that you are actually interested in and secondly is there enough information for you to gather to be able to write your literature review in the future so that first step your first step of your research process is thinking about the topic because without a topic you there's nothing you can't do anything else so the first step has to always be to find a topic and think about it now once you've thought about a topic and you've narrowed it down to the thing that you're interested in at this stage you will then go to your supervisor to your lecturer to your professor to your mentor to your tutor and you will ask them do you think this is a good topic and that is where you will get some feedback and most likely you'll have to go back have another think or try to refine a bit more or try to think about it in a different way but that is always the first step. In the video that I make about finding a good topic we'll talk about it in a lot more depth but to start off with to introduce this is always the first step. So the second step is to identify a problem and this is what we like to call in as you know in research the gap in literature. So a problem slash gap in literature is the part of research that we that is missing. So when you do research in fact in order to graduate from a PhD you have to and this is one of the criteria you have to produce research it has to be in a thesis or in a in a published paper it has to be research it has to be a finding that is new something that we do not know before we did not know before your research right and that is the number one criteria for for actually getting a phd it is the fact that it has to be something new has to be something novel that you have discovered okay so you need to think about the gap in literature where is there a missing piece i understand this i understand that we know this we know that but what is there that we don't quite know and that is the bit that you are then going to try to identify during your research process right chosen a topic now we need to find the problem where is the missing information now in order to do this you need to have read a lot of papers around your topic. So that's why I said initially, you need to have had approval from your committee, from your tutor, your supervisor to say, right, that's okay. It's good for me to go there. Now you've got that topic that you're looking at. You then want to try to find the gap. Where are you going to slot in? What is it that you are going to provide in terms of knowledge? Now, the identifying a problem is actually quite an important and quite critical part of the research process it's almost impossible you to continue on with your research without having identified the problem because if you don't have a problem you don't know what it is you're looking at you don't know what methods you're using you don't know what your research question is going to be or your hypothesis so at this stage you have to have a very well-defined research problem and your question in order to continue on to the next steps so when i say research problem and we'll talk about this more in in the following video that i'm going to produce about it but when i talk about research problem it could be a number of different things so it could be that we understand or we have the knowledge of a certain situation but now you're comparing it to a different situation so it could be more theoretical where you're comparing two things to each other that haven't been compared before so that would be fine as long as what you have is something original or you may be trying to explore a specific relationship let's say for example in my case with my PhD I was looking at two different proteins and the relationship between them so that is one type of research that you can do as well and so just think about your topic and think about where the gap is in the literature you have to read a lot to be able to find this and a question I get a lot emailed to me and directed to me is about this problem so how do I find a problem like how do i find a gap in literature and it's almost impossible for me to to give you any answers because i have to have read all the papers within your topic in order to answer that question which is almost impossible so it's something that you have to do independently and you can always discuss with me you can discuss kind of trying to refine that question but for the most part you need to read around your subject yourself to get that question then step number three is to actually write down your research question now this is usually in the form maybe of a hypothesis or maybe it could be just a you know a standalone question so this is just you saying this is what i'm looking at so i'm looking at whether actin and myosin bind together to have an impact on the motility of the cortex like that is my question and then i'll have a hypothesis saying actin and myosin bind together and they do this so this is just my question and you're just following on from your problem so you've identified your topic you found the problem the gap in literature and then you write down what your question is so what it is exactly that you are looking for and this will be like your guiding star this will be the thing the question the statement that you have at the top you know at the top of your mind whenever you are looking at literature whenever you're writing a literature review whenever you speak to someone you have that question in mind and so that needs to be something that's really well defined it should also be really specific so it can't just be saying is obesity caused by i don't know fatty food i'm just giving a random example that is too vague is obesity in children in male in female different ages what fatty foods what like you need to be very very specific so specific that someone else should be able to pick up your research question and know what it is you're looking at they need to be able to know sort of what methods you're using is it qualitative or is it quantitative what type of research are you actually doing that should really be in the research question so a good research question is one where that is really well defined then step number four is to write a research design so this is where you're kind of creating a bit of a method a bit of a process within a process so you are now writing down and you're now thinking about how you're going to conduct this research so to follow this will be the research proposal but at this stage here you're just thinking about your research design so how are you going to get this research done what are the factors that you need to think about who are the people the participants that you may need are you doing a lab-based thing do you need cells are you you know what do you need humans do you need animals is it just a review paper so do you just need to think about researchers out there what kind of study are you going to conduct in order to find out the results and the answer to your question essentially the research design is a practical framework so it's giving laying out that frame for you in order to answer your research question. And here, it's more of a thinking process. It's more of a discussion. You might want to ask your supervisor, you might want to ask your tutor to talk about it. How are we going to get the answer to this question? And then to finish off the research process, you now want to write a research proposal. And I have a really good video about this, and I'll leave the link for it down below, where you are detailing all the steps for your research so you're detailing your the background of your research the literature review and you're justifying that there is a need for this research you then want to detail your methods your materials the aim your you know your timeline how long it's going to take you to do these things and then that document is what you take with you to your supervisor and say look this is my research proposal you might take it to a potential phd supervisor and say look this is what i've found and this is what i'm really interested in and here is the proposal and you have it all outlined there for you or it's a document that you're able to use in order to build upon your dissertation and so if you're writing an essay dissertation you are able to use that as well so with your research proposal you are detailing the context you are detailing the purpose the plan and your aims the whole process going from finding a topic finding a problem finding the research question defining the actual research and then now you're compiling all of that and you're putting it into a document called the research proposal and all of this information is in there someone should be able to pick that up see what you found find the review of the literature and say right this is a good study this is a good bit of research we are going to approve this and then you can go on and plan the rest of your research so i hope this video helped you summarizing the steps of the research process to begin with and as i mentioned i'm going to be doing each of these five steps as single videos so i can expand on them and i'll make it into a playlist so you're able to sort of follow up and click on the next couple videos but for now i hope this did help with thinking about the research process and thinking about maybe what stage you are at if you are at any of them if you do want further support you can contact me on thepagedoctor.com where i give support and we have a team of consultants top consultants and top editors that can support you through the process of writing your research proposal or even through the post process of thinking about how you're going to find a gap in literature how you're going to find you know your hypothesis and define that for you so don't forget to leave me a comment and let me know if this was helpful and don't forget to leave me a thumbs up and subscribe to see more from me and I'll see you in my next one. Bye.

Economics JIW - Tips for Choosing a Topic: Home

Choosing a topic.

Choosing a topic that can answer an economic research question is challenging. Some tips:

Ripped from the headlines rarely makes a good economic paper. You will be using data to determine causation or correlation. Sometimes a similar event can be used. Topics such as artificial intelligence may make a good policy paper but not a good economic one due to lack of data.
Literature Review: Your JIW should use primarily scholarly sources. Start with Econlit (the database of the American Economic Association). Econlit indexes major journals, working papers, conference proceedings, dissertations, and chapters in critical books. It takes a long time for scholarly literature to appear. Preprints are called working papers in economics and major ones are indexed in Econlit. Y ou are your own research team and have limited time. Many articles are written over a couple of years and involve many people gathering and cleaning the data. Some starting places: see https://libguides.princeton.edu/econliterature/gettingstarted
Outside of finance and some macroeconomic data, most data will not have many points in time. Data determines the methods used . While a linear regression can be great for time series data, it is likely not what you will use for survey data.
Longitudinal or panel study : same group of individuals is interviewed at intervals over a period of time. This can be very useful to observe changes over time. Keep in mind when using a long running longitudinal dataset that the panel generally is not adding new participants so may not reflect today’s demographics.
Cross-sectional study : data from particular subjects are obtained only once. While you are studying different individuals each time, you are looking at individuals with similar demographic characteristics. Demography is typically rebalanced to reflect the population.
Summary statistics : aggregated counts of survey or administrative data.
Typically around a 2 year time lag from the time the survey data is collected to the time of release. The Economic Census and Census of Agriculture take about 4 years for all data to be released. Many surveys never release the microdata.
Very little subnational data is available and is often restricted when available. State level macro data for the United States is more prevalent. City level data is often a case study or only available for very large cities.
Many micro-level datasets are restricted. It is not uncommon to wait a year before getting permission or denial to use the data. Each organization has its own rules.
Historical data in electronic format prior to 1950 is rare. Most governmental links provide current data only.
What is measured changes over time . Do not assume modern concepts were tracked in the past. Definitions of indicators often change over time.
Data cannot be made more frequent. Many items are collected annually or even once a decade. Major macroeconomic indicators such as GDP tend to be quarterly but some countries may only estimate annually.
What exists for one country may not exist for another country. Data is generally inconsistent across borders .
Documentation is typically in the native language .
Always look at the methodology. The methodology section is one of the most important parts of the paper. Someone should be able to replicate your work. Describe the dataset and its population. Describe how the data was subset, any filters used, and any adjustment methods. While you are likely not trying to publish in American Economic Review or Journal of Finance , these are the gold standards. See how they layout the articles and in particular the methodology and data sections.
The basic question to ask when looking for economic data is " who cares about what i am studying ?" Unfortunately, the answer may be no one. Ideally, look for an organization that is concerned with your research as part of its mission. Examples include the International Labor Organization or the Bureau of Labor Statistics focusing on labor research; the International Monetary Fund or the Board of Governors of the Federal Reserve System focusing on monetary and fiscal concerns; the World Bank focusing on development; and the World Health Organization focusing on health. This does not mean these organizations collect data on all topics related to that field.
Find a topic for which there is literature and data but allows room to add a contribution. Topics such as sports and music are popular due to personal interests but may not make good research topics due to lack of data and overuse.

More tips:

Data is typically not adjusted for inflation. It is usually presented in current (nominal) currency. This means the numbers as they originally appeared. When data has been adjusted for inflation (constant or real), a base year such as 2020 or 1990 will be shown. If a base year is not provided, then data is current and therefore not adjusted for inflation. If given a choice, choose current dollars. Data is often derived from different datasets and many will use different base years. Adjust everything at the end. It is easier than doing reverse math!
While most datasets are consistent within the dataset for currency used such as all in US Dollars or Euro or Japanese Yen or each item in local currency, some will mix and match. LCU is a common abbreviation meaning local currency units. Consider looking at percent changes rather than actual values. If adjusting use the exchange rate for each period of time, not the latest one.
Economic indicators may be either seasonally adjusted or not seasonally adjusted. This is very common for employment and retail sales. Unless something says it is seasonally adjusted, it is not. Be consistent and note in methodology.

Librarians are here to help! Librarians can help to devise a feasible topic, assist with the literature search, and choose appropriate data. Your data may fall into multiple categories. Think of the primary aspect of your topic in terms of first contact. Do not email librarians individually. If unsure who to contact either put all that apply on same email or email just one. If that person is not the best, they will refer you.

Bobray Bordelon Economics, Finance, & Data Librarian [email protected]

Charissa Jefferson

Labor Librarian [email protected]

Mary Carter Finance and Operations Research Librarian [email protected]

Data workshops

Environmental and energy data (Bordelon), 9/23/2024 - 7:30-8:50 pm
Health, Crime and other Socioeconomic Data (Bordelon), 9/23/2024 and 10/02/2024 - 3-4:20 pm
Macroeconomics and trade data (Bordelon), 9/25/2024 and 9/30/2024 - 3-4:20 pm
Finance data (Carter), 9/23/2024 and 9/25/2024 - 3-4:20 pm
Labor and education data (Jefferson), 9/23/2024 and 9/25/2024 - 3-4:20 pm

Workshops listed twice have the same content and are done as an opportunity to fit your schedule. While you must attend at least one data workshop, it is wise to attend more than one. If in a certificate program, with the exception of political economy which has to be incorporated into your JIW, other programs have different requirements which are typically for your senior year. As an example, if in finance, if you choose not to explore a finance topic this year you will still need to incorporate in your senior theses so try and attend a finance workshop in addition to your topical workshop for your JIW since these are intended to help you for your time at Princeton and both the JIW but also the senior thesis.

Last Updated: Aug 28, 2024 9:32 AM
URL: https://libguides.princeton.edu/ECOJIWTopics

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Study reveals the benefits and downside of fasting

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Low-calorie diets and intermittent fasting have been shown to have numerous health benefits: They can delay the onset of some age-related diseases and lengthen lifespan, not only in humans but many other organisms.

Many complex mechanisms underlie this phenomenon. Previous work from MIT has shown that one way fasting exerts its beneficial effects is by boosting the regenerative abilities of intestinal stem cells, which helps the intestine recover from injuries or inflammation.

In a study of mice, MIT researchers have now identified the pathway that enables this enhanced regeneration, which is activated once the mice begin “refeeding” after the fast. They also found a downside to this regeneration: When cancerous mutations occurred during the regenerative period, the mice were more likely to develop early-stage intestinal tumors.

“Having more stem cell activity is good for regeneration, but too much of a good thing over time can have less favorable consequences,” says Omer Yilmaz, an MIT associate professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and the senior author of the new study.

Yilmaz adds that further studies are needed before forming any conclusion as to whether fasting has a similar effect in humans.

“We still have a lot to learn, but it is interesting that being in either the state of fasting or refeeding when exposure to mutagen occurs can have a profound impact on the likelihood of developing a cancer in these well-defined mouse models,” he says.

MIT postdocs Shinya Imada and Saleh Khawaled are the lead authors of the paper, which appears today in Nature .

Driving regeneration

For several years, Yilmaz’s lab has been investigating how fasting and low-calorie diets affect intestinal health. In a 2018 study , his team reported that during a fast, intestinal stem cells begin to use lipids as an energy source, instead of carbohydrates. They also showed that fasting led to a significant boost in stem cells’ regenerative ability.

However, unanswered questions remained: How does fasting trigger this boost in regenerative ability, and when does the regeneration begin?

“Since that paper, we’ve really been focused on understanding what is it about fasting that drives regeneration,” Yilmaz says. “Is it fasting itself that’s driving regeneration, or eating after the fast?”

In their new study, the researchers found that stem cell regeneration is suppressed during fasting but then surges during the refeeding period. The researchers followed three groups of mice — one that fasted for 24 hours, another one that fasted for 24 hours and then was allowed to eat whatever they wanted during a 24-hour refeeding period, and a control group that ate whatever they wanted throughout the experiment.

The researchers analyzed intestinal stem cells’ ability to proliferate at different time points and found that the stem cells showed the highest levels of proliferation at the end of the 24-hour refeeding period. These cells were also more proliferative than intestinal stem cells from mice that had not fasted at all.

“We think that fasting and refeeding represent two distinct states,” Imada says. “In the fasted state, the ability of cells to use lipids and fatty acids as an energy source enables them to survive when nutrients are low. And then it’s the postfast refeeding state that really drives the regeneration. When nutrients become available, these stem cells and progenitor cells activate programs that enable them to build cellular mass and repopulate the intestinal lining.”

Further studies revealed that these cells activate a cellular signaling pathway known as mTOR, which is involved in cell growth and metabolism. One of mTOR’s roles is to regulate the translation of messenger RNA into protein, so when it’s activated, cells produce more protein. This protein synthesis is essential for stem cells to proliferate.

The researchers showed that mTOR activation in these stem cells also led to production of large quantities of polyamines — small molecules that help cells to grow and divide.

“In the refed state, you’ve got more proliferation, and you need to build cellular mass. That requires more protein, to build new cells, and those stem cells go on to build more differentiated cells or specialized intestinal cell types that line the intestine,” Khawaled says.

Too much of a good thing

The researchers also found that when stem cells are in this highly regenerative state, they are more prone to become cancerous. Intestinal stem cells are among the most actively dividing cells in the body, as they help the lining of the intestine completely turn over every five to 10 days. Because they divide so frequently, these stem cells are the most common source of precancerous cells in the intestine.

In this study, the researchers discovered that if they turned on a cancer-causing gene in the mice during the refeeding stage, they were much more likely to develop precancerous polyps than if the gene was turned on during the fasting state. Cancer-linked mutations that occurred during the refeeding state were also much more likely to produce polyps than mutations that occurred in mice that did not undergo the cycle of fasting and refeeding.

“I want to emphasize that this was all done in mice, using very well-defined cancer mutations. In humans it’s going to be a much more complex state,” Yilmaz says. “But it does lead us to the following notion: Fasting is very healthy, but if you’re unlucky and you’re refeeding after a fasting, and you get exposed to a mutagen, like a charred steak or something, you might actually be increasing your chances of developing a lesion that can go on to give rise to cancer.”

Yilmaz also noted that the regenerative benefits of fasting could be significant for people who undergo radiation treatment, which can damage the intestinal lining, or other types of intestinal injury. His lab is now studying whether polyamine supplements could help to stimulate this kind of regeneration, without the need to fast.

“This fascinating study provides insights into the complex interplay between food consumption, stem cell biology, and cancer risk,” says Ophir Klein, a professor of medicine at the University of California at San Francisco and Cedars-Sinai Medical Center, who was not involved in the study. “Their work lays a foundation for testing polyamines as compounds that may augment intestinal repair after injuries, and it suggests that careful consideration is needed when planning diet-based strategies for regeneration to avoid increasing cancer risk.”

The research was funded, in part, by Pew-Stewart Scholars Program for Cancer Research award, the MIT Stem Cell Initiative, the Koch Institute Frontier Research Program via the Kathy and Curt Marble Cancer Research Fund, and the Bridge Project, a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center.

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A new study led by researchers at MIT suggests that fasting and then refeeding stimulates cell regeneration in the intestines, reports Katharine Lang for Medical News Today . However, notes Lang, researchers also found that fasting “carries the risk of stimulating the formation of intestinal tumors.”

Prof. Ömer Yilmaz and his colleagues have discovered the potential health benefits and consequences of fasting, reports Max Kozlov for Nature . “There is so much emphasis on fasting and how long to be fasting that we’ve kind of overlooked this whole other side of the equation: what is going on in the refed state,” says Yilmaz.

MIT researchers have discovered how fasting impacts the regenerative abilities of intestinal stem cells, reports Ed Cara for Gizmodo . “The major finding of our current study is that refeeding after fasting is a distinct state from fasting itself,” explain Prof. Ömer Yilmaz and postdocs Shinya Imada and Saleh Khawaled. “Post-fasting refeeding augments the ability of intestinal stem cells to, for example, repair the intestine after injury.”

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How early-stage cancer cells hide from the immune system

MIT biologists found that intestinal stem cells express high levels of a ketogenic enzyme called HMGCS2, shown in brown.

Study links certain metabolites to stem cell function in the intestine

Intestinal stem cells from mice that fasted for 24 hours, at right, produced much more substantial intestinal organoids than stem cells from mice that did not fast, at left.

Fasting boosts stem cells’ regenerative capacity

“Not only does the high-fat diet change the biology of stem cells, it also changes the biology of non-stem-cell populations, which collectively leads to an increase in tumor formation,” Omer Yilmaz says.

How diet influences colon cancer

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Today, the U.S. Food and Drug Administration approved and granted emergency use authorization (EUA) for updated mRNA COVID-19 vaccines (2024-2025 formula) to include a monovalent (single) component that corresponds to the Omicron variant KP.2 strain of SARS-CoV-2. The mRNA COVID-19 vaccines have been updated with this formula to more closely target currently circulating variants and provide better protection against serious consequences of COVID-19, including hospitalization and death. Today’s actions relate to updated mRNA COVID-19 vaccines manufactured by ModernaTX Inc. and Pfizer Inc.

In early June, the FDA advised manufacturers of licensed and authorized COVID-19 vaccines that the COVID-19 vaccines (2024-2025 formula) should be monovalent JN.1 vaccines. Based on the further evolution of SARS-CoV-2 and a rise in cases of COVID-19, the agency subsequently determined and advised manufacturers that the preferred JN.1-lineage for the COVID-19 vaccines (2024-2025 formula) is the KP.2 strain, if feasible.

“Vaccination continues to be the cornerstone of COVID-19 prevention,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “These updated vaccines meet the agency’s rigorous, scientific standards for safety, effectiveness, and manufacturing quality. Given waning immunity of the population from previous exposure to the virus and from prior vaccination, we strongly encourage those who are eligible to consider receiving an updated COVID-19 vaccine to provide better protection against currently circulating variants.”

The updated mRNA COVID-19 vaccines include Comirnaty and Spikevax, both of which are approved for individuals 12 years of age and older, and the Moderna COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine, both of which are authorized for emergency use for individuals 6 months through 11 years of age.

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Unvaccinated individuals 6 months through 4 years of age are eligible to receive three doses of the updated, authorized Pfizer-BioNTech COVID-19 Vaccine or two doses of the updated, authorized Moderna COVID-19 Vaccine.
Individuals 6 months through 4 years of age who have previously been vaccinated against COVID-19 are eligible to receive one or two doses of the updated, authorized Moderna or Pfizer-BioNTech COVID-19 vaccines (timing and number of doses to administer depends on the previous COVID-19 vaccine received).
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Individuals who receive an updated mRNA COVID-19 vaccine may experience similar side effects as those reported by individuals who previously received mRNA COVID-19 vaccines and as described in the respective prescribing information or fact sheets. The updated vaccines are expected to provide protection against COVID-19 caused by the currently circulating variants. Barring the emergence of a markedly more infectious variant of SARS-CoV-2, the FDA anticipates that the composition of COVID-19 vaccines will need to be assessed annually, as occurs for seasonal influenza vaccines.

For today’s approvals and authorizations of the mRNA COVID-19 vaccines, the FDA assessed manufacturing and nonclinical data to support the change to include the 2024-2025 formula in the mRNA COVID-19 vaccines. The updated mRNA vaccines are manufactured using a similar process as previous formulas of these vaccines. The mRNA COVID-19 vaccines have been administered to hundreds of millions of people in the U.S., and the benefits of these vaccines continue to outweigh their risks.

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The approval of Comirnaty (COVID-19 Vaccine, mRNA) (2024-2025 Formula) was granted to BioNTech Manufacturing GmbH. The EUA amendment for the Pfizer-BioNTech COVID-19 Vaccine (2024-2025 Formula) was issued to Pfizer Inc.

The approval of Spikevax (COVID-19 Vaccine, mRNA) (2024-2025 Formula) was granted to ModernaTX Inc. and the EUA amendment for the Moderna COVID-19 Vaccine (2024-2025 Formula) was issued to ModernaTX Inc.

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Day One: Placebo Workshop: Translational Research Domains and Key Questions

July 11, 2024

Welcome Remarks

ERIN KING: All right. We'll go ahead and get started. On behalf of the co-chairs and the NIMH planning committee, I'd like to welcome you to the NIMH Placebo Workshop: Translational Research Domains and Key Questions.

Before we begin, I'm going to quickly go through a few housekeeping items. All attendees have been entered into the workshop in listen-only mode with cameras disabled. You can submit your questions via the Q&A box at any time during the presentation. And be sure to address your question to the speaker that you'd like to respond. For more information on today's speakers, their biographies can be found on the event registration website.

If you have technical difficulties hearing or viewing the workshop, please note these in the Q&A box and our technicians will work to fix the problem. You can also send an email to [email protected]. And we'll put that email address in the chat box. This workshop will be recorded and posted to the NIMH event website for later viewing.

Now I'd like to turn it over to the acting NIMH Director, Dr. Shelli Avenevoli for opening remarks.

I think the audio is still out. If we can restart the video with the audio turned up.

TOR WAGER: That was some placebo audio. I think I might be able to share my screen and get the audio to come up on the video. So maybe I can try that. Hopefully you can see this okay. Let's see if it comes through.

SHELLI AVENEVOLI: Good morning. I'm excited to be here today to kick off the NIMH Placebo Workshop. I am currently the Acting Director of NIMH, and I look forward to serving in this role while NIMH conducts a national search for the next NIMH Director.

Today we are bringing together experts in neurobiology, clinical trials and regulatory science to examine placebo effects in drug devices and psychosocial interventions. NIMH has long understood that the placebo phenomenon is highly active in studies of mental illness. Understanding how to design and interpret clinical trial results as well as placebo neurobiological mechanisms have been important research questions that still have significant gaps. Subsequently, I'm eager to learn what you believe are the most important questions of placebo research and how they might be answered. This is no small charge, I understand. But our organizers have designed a carefully thought out agenda to help facilitate our success.

The workshop is organized into domains that aim to identify those important questions. I'm looking forward to hearing a historical review of the successes and failures around mitigating the placebo response in both academic and industry research. This includes historical perspectives in drug and device trials, understanding psychosocial aspects of the placebo response and measuring and mitigating the placebo effect.

Clearly, several perspectives will be discussed during these presentations. It will be exciting to hear your individual views as well as the panel discussions. I'd like to thank Doctors Tor Wager and Cristina Cusin, the co-chairs of the workshop, as well as the rest of the planning committee for their work in organizing this excellent agenda.

I will now turn it over to Dr. Tor Wager. Thank you.

Introduction and Workshop Overview

TOR WAGER: Okay. Hi, everybody. Sorry the audio didn't turn out as well as we had hoped, but I hope you could still hear it to some degree. And I just want to say I'm really delighted to have you all here. And I'm really delighted that NIMH has decided to organize this workshop and has worked so hard in planning it.

I'd like to thank my co-chair Cristina and also the NIHM co-leads Erin King and Doug Meinecke as well as the rest of the team that's been working really hard on preparing this meeting, including Meg Grabb and Laura Rowland and Alex Talkovsky, Mi Hillefors and Arina Knowlton.

My job for the next few minutes is just to give you a brief overview of the -- some of the main concepts in the placebo field altogether. And I'm going to start really at the very, very beginning.

The workshop goals are really to understand how placebo and nocebo effects impact clinical trial design and outcomes; to understand some of the psychological, neurobiological, and social mechanisms that underlie placebo effects.

And we'd like to think together to use this understanding to help to identify and maximize therapeutic effects of drugs and devices. And that means better clinical trial designs, better identification of outcomes, and also to harness placebo mechanisms in clinical care alongside active treatments so that we don't think of only specific treatments, we think of treatments as having psychological and psychosocial components as well as active drug or device components.

And to go back to the very, very beginning, my colleague Ted Kaptchuk once wrote that the history of medicine is the history of the placebo effect. So this is the Ebers Papyrus circa 1500BCE and it documents hundreds of ancient medications that are now thought to be little better than or no better than placebo effects. Some of them we recognize today like, for example, opium, the ingredient of opiates; and wormwood, the ingredient of absinthe for headache.

If you were poisoned, you might be treated with crushed up emerald or Bezoar stone which is undigested material from the intestines of animals. You might be treated with human sweat and tapeworms and feces, moths scraped from the skull of a hung criminal, or powdered Egyptian mummy, among many other treatments. And what all of these have in common is that none of them or very few of them have active ingredients in terms of specific effects, but they all act on the mind and brain of the perceiver. And so there is something about the beliefs and the imagination of the person that has made these treatments persist for many, many centuries.

And this provides both a challenge and an opportunity. I'm going to introduce the challenge with this clinical trial which is a gene therapy for Parkinson's disease AZ neurokinin which was an industry funded trial. And they went out two years. And this is a genetic manipulation intervention for Parkinson's disease. And what you see here is an improvement in motor scores in PDRS3 on Parkinson's. And if you see, people getting the active treatment, they got substantially better within the first six months and they stayed better for two years.

And this seems great. But the problem is that this trial failed. And the failure resulted in the drug company being sold off and this treatment may never see the light of day. And that's because people in the placebo group also got better and stayed better for two years. And there was no drug placebo difference.

And this is really shocking to me because Parkinson's is a neurodegenerative disorder. And so it's very surprising to see changes of this magnitude last this long. So the opportunity is in harnessing these psychosocial processes and the active ingredients that go into the placebo index like this, or placebo responses like this I should say. And the challenge, of course, is that placebo responses can mask effects of treatment in the way that we've seen here.

And this is not a unique occurrence. In many cases, there are treatments that are widely used that are Medicare reimbursed that turn out after they are tested later to not be better than placebo in clinical trials, randomized trials. And this includes arthroscopic knee surgery for arthritis, vertebroplasty, epidural steroid injections which are still practiced widely every day. Some other interesting ones like stents for angina, which is chest pain. And also some recent high profile failures to beat placebo after very initially promising results in emerging treatments like gene therapy for Parkinson's disease that I mentioned before and deep brain stimulation for depression.

A recent interesting case is the reversal of FDA approval for phenylephrine which is a very common nasal decongestant. It's the most widely used decongestant on the market. Almost $2 billion in sales. So it turns out, it may not be better than the placebo. One of the problems is that in some areas like, for example, in chronic pain, placebo effects are growing across time but drug effects are not. And so the drug placebo gap is shrinking and fewer and fewer treatments are then getting to market and getting through clinical trials.

And that's particularly true in this study by Alex Tavalo in the United States. So as an example, surgery has been widely practiced first in an open label way where people know what they are getting. And it was only much later that people started to go back and do trials where they would get a sham surgery that was blinded or just a superficial incision then. So the person doesn't know that they are not getting the real surgery. And those sham surgeries in many cases have effects that are substantial and in some cases as large or nearly as large as the active placebo -- as the active drug effects.

So this is what we call placebo response which is overall improvement on placebo. It doesn't mean that the sham surgery or other placebo treatment caused them to get better.

And so if we think about what the placebo response is, it's a mixture of interesting and uninteresting effects including regression to the mean, people fluctuate in their symptoms over time. And they tend to enroll sometimes when the symptoms are high. And there is sampling bias and selective attrition. There is natural history effects. And then there is the placebo effect which we'll define as a causal effect of the placebo context.

And the simplest way to identify a placebo effect is to compare placebo treatment with a natural history or no treatment group in a randomized trial. So here in this three-arm trial, a parallel groups trial, what you see is the typical way of identifying the effect is the active drug effect comparing active treatment to placebo. And you need to compare placebo to the natural history group to identify the placebo effect here.

And if we look at those studies that do such comparisons, we can see that there are many effects across different areas. And those effects are active brain body responses or mental responses to the treatment in context. And so there are many ingredients. It's not the placebo drug or stimulation or device itself, of course, that has the effect. It's the suggestions and the context surrounding that.

And there are many types of cues. There are verbal suggestions, information, there are place cues, there are social cues including body language and touch. There are specific treatment cues that are associated with the drugs. And there is a rich internal context. Expectations about treatment outcomes, interpretations of the meaning of what symptoms mean and the meaning of the therapeutic context and the care context. As well as engagement of emotions and memories. And what I'm calling here precognitive associations that are learned or conditioned responses in the brain and the body. So there is a large family of placebo effects; not one, but many placebo effects. They operate both via conscious and unconscious means. They are embedded in the nervous system through learning processes. And an idea here is that meaning of the response to the treatment to the person and the symptom is really the key. What are the implications of the cues and the symptoms and the whole context for future well being? o if we look at studies that have isolated placebo effects compared to no treatment, we see that there are many studies and many systematic reviews and meta analysis including many types of clinical pain in depression, in Parkinson's disease, in motor symptoms as well as other symptoms. In anxiety including social anxiety in particular and general anxiety. Substance misuse and perceived drug effects. Some effects in schizophrenia. Potentially some effects in asthma. And that is a sort of a tricky thing with the conflicting results that we could talk about. And effects on sleep and cognitive function and more. So these effects are really widespread.

There have been some attempts to decompose these into, you know, how large are the effects of placebo versus the effects of active drugs. And so if you look at pharmacotherapy for depression, at least in one analysis here by Irving Kirsch, half of the overall benefit, the placebo response -- or the active treatment response, I should say, is placebo. A very small proportion is specific drug effects. And about a quarter of it is people who would have gotten better anyway, they recover spontaneously from depression. That's natural history.

So the placebo effect is a large part of the overall therapy response. And this mirrors what's called common factors in psychotherapy. And common -- and this is for mood and anxiety disorders, substance use disorders and more. And common factors are those therapeutic elements that are shared across many treatments. And really in particular to -- they include drug and therapy, providing listening and social support, positive engagement and positive expectations. And in this analysis here the common factors also were responsible for a lion's share of the therapeutic effects of psychotherapy.

So in one sense you can say that placebo effects are really powerful, they can affect many kinds of outcomes. But there is continuing controversy, I would say. Even though these competing "New York Times" headlines are somewhat old now. And this latter headline came out after a landmark meta analysis in Froberg, Jenning, Kaptchuk in 2001 which they've updated several times since then.

And what they found is consistent with what I said. There are significant placebo effects in the domains that they were powered to detect. But they discounted those. They said it's probably due to reporting bias and other kinds of biases. So this is a key question is which outcomes count as important?

So here is an example from a fairly recent study of expectancy effects in anxiety. They compare it, people getting an SSRI in a typical open label way which is in the blue line with people who got a hidden SSRI, they didn't know that they were getting the SSRI. And that difference is a placebo-like effect or an expectancy effect.

There was a substantial drop in anxiety that was caused by getting the knowledge that you -- that people were being treated. So the question is does that actually count as a meaningful effect? And, you know, I think there's -- it's right to debate and discuss this. It relates to this idea of what I'll call heuristically depth. That this effect might simply be people telling us what we want to hear. That's a communication bias or a so-called demand characteristic that's been studied since the '50s.

It could be an effect on how people feel and their decision making about how they report feelings. It could be an effect on the construction and anxiety in the brain. It could be an effect on -- a deeper effect in potentially on some kind of lower level pathophysiology, some kind of effect on the organic causes of anxiety.

So the gold standard has been to look for these organic causes. And it gets very tricky when you define outcomes in terms of symptoms. Like is true with pain, with depression-related symptoms, anxiety-related symptoms and more in mental health. In pain, what the field has been trying to do is to look at pathways that are involved in early perceptual effects of nociception and on those central circuits that are involved in constructing the pain experience to ask if those are affected. And what we've seen, this is sort of the most developed area I think in human neuroscience of placebo effects. And we see reduced responses to painful events in many relevant areas. Including in the spinal cord areas in some studies that are known to give rise to nociceptive input to the brain.

There is increases in activity in punitive pain control systems that send descending projections down to the spinal cord. And there is release of endogenous opioids with placebo treatment in some of those pain control systems and other areas of the frontal cortex and forebrain. So these are all causal effects of placebo treatment that seem to be relevant for the construction of pain.

And what is remarkable is that the effects in the frontal cortex that are the most reliably influenced by placebo including the medial prefrontal cortex and the insula and other areas really are not just involved in pain, of course. They really affect some systems that are involved in high-level predictive control of motivation, decision making and perception.

So an emerging concept is this idea that what these circuits are for and what a lot of our brain is for in general is forming a predictive model of what is going to happen to us, what situation do we find ourselves in. So these cortical circuits are important for representing hidden states that we have to infer. And that's another way of saying meaning. Therefore, understanding what the meaning of events is. If it's an eye gaze, what is the meaning of that look? If it's a movement, what is the underlying meaning of the movement?

And it's that underlying situation model, predictive model that guides how we respond to a situation and what we learn from experience. So these systems in the brain that are influenced by placebo provide joint control over perception, over behavior and decision making including whether we choose to smoke or not smoke or eat more or eat less. And the body through the autonomic and neuroendocrine and immune systems. So broadly speaking, there is this joint control.

So this is one example where we can get closer to pathophysiology with some forms of placebo effects. And this is forebrain control over all of the various brainstem and spinal centers that are important for particular kinds of regulation of the body. The respiratory muscles, the heart, the intestines, and immune responses as well. When we look in the brain, the most consistent correlates in meta analyses of immune changes in the body are those that seem to play central roles in placebo effects as well like the ventromedial prefrontal cortex.

And another important development in this and aspect of this is the idea of parallel models in nonhuman animals and in humans, particularly those that use classical conditioning. So there are many kinds of pharmacological conditioning in which a cue is paired with a drug over time, usually over several days. And then the cues alone like the inscription alone can come to enlisted effects that sometimes mimic drug effects and sometimes are compensatory responses that oppose them.

And one of the most famous was the phenomenon of conditioned immunosuppression that was first published by Bob Ader in 1976 in Science and has since been developed quite a lot. So this is from a review by Mia Chelowoski's group which is a very comprehensive review of different kinds of immunosuppressive responses. And the point I want to make here is that there is increasing evidence that the insular cortex as an example is really important for storing memories about context that then get translated into effects on cellular immunity that are relevant for the trajectory of health and disease in broad ways. And those areas of the insula are similar to those that are involved in placebo effects in humans on pain, itch, cough, disgust and other conditions as well. So there is the potential here for memories that are stored in the cortex to play out in very important ways in the body. And that can influence mental health directly and indirectly as well.

And I want us to move toward wrapping up here with a couple of ideas about why these effects should exist. Why do we have placebo effects in the first place? And two ideas are that we need them for two reasons. One is for predictive control. The idea about what we need an evolved brain for, a highly developed brain is to anticipate those threats and opportunities in the environment and respond in advance. So it's not that we -- we don't respond to the world as it is. We really respond to the world as it could be or as we think it will be.

And the second principle is causal inference. That we -- what is less relevant is, is the particular sensory, you know, signals that are hitting our apparatus at any one time. And what is really more important is the underlying state of the body and the world, what is happening.

Just to illustrate those things, one example from Peter Sterling is this very complicated machinery for regulating blood pressure when you stand up and when you are under psychological stress. And we need this complex set of machinery in order to predict what the current -- what the future metabolic demands are. So our blood pressure essentially like other systems responds in advance of challenges. And that's why we get stressed about a lot of physiology.

An example of the second is a simple example from vision. If you look at these two squares that we circled here, you can see they probably look like they are different colors. One is brighter and one is darker. But if I just take away the context, you can see that the squares are exactly the same color. And so you don't see the color of the light hitting your retina. What you see is your brain's guess about the underlying color of the paint or the color of the cubes that discounts illumination and factors it out as a cause. So what our perceptual systems are doing is causal inference.

So with pain, itch or nausea, for example, other symptoms, you don't -- or mood or motivation, you don't feel your skin or your stomach or your body in a direct way. Your brain is making a guess about the underlying state from multiple types of information. And this really starts with our memories and past associations and our projections about the future.

So I'm using pain as an example because we study it a lot. But the idea is that the pain really starts with these projections about the future. And there is a representation in the brain of the current state of threat and safety, if you will. Nociceptive input from the body plays some role in that, but it's really the central construction that integrates other forms of context, what is the look, what kind of support are you getting, that together determines what we end up feeling.

And there are different kind of responses that are linked to different parts of that system. But the idea of suffering and well being, of fatigue and motivation, all of those things I think are related to the current state.

There are many open questions. You know, one is which outcomes count as important for determining whether an intervention is meaningful? Can we separate changes on decision making and suffering from response biases that we really shouldn't consider important for clinical research.

Secondly, can we identify outcomes affected by real treatments, drugs and devices but not placebos? And how can we use those outcomes in clinical trials in advance of the regulatory front as well on the scientific front?

Third, what kinds of experimental designs will help us separate specific effects from these broader context effects? And is this a reasonable goal? Can we actually separate them or do they often work together or synergize with one other? So do they interact?

Fourth, can we predict who will be a placebo responder from personality, genetics perhaps, or brain responses? Can we use this to maximize our treatment effects in clinical trials and improve the pipeline? And, you know, unclear whether that is possible.

And finally, how can we use all of these factors we've discussed alongside other treatments that are current medical treatments to improve outcomes?

With that, I'm just going to introduce the next -- the rest of today. I realize we're a little bit long getting started. Hopefully we can make up some time here. But now we're going to start our first session which is about perspectives on placebo in drug trials from Michael Detke and Ni Khin and Tiffany Francione. So this is going to be about the sort of history and state of how placebo effects interface with the regulatory environment.

Then we'll take a break. And after that we'll continue to the rest of the sessions. So without further ado, I would like to turn it over to Mike. Thank you.

Historic Perspectives on Placebo in Drug Trials

MICHAEL DETKE: I think Ni is going before me. Correct, Ni?

NI AYE KHIN: Yes, I am.

MICHAEL DETKE: Okay, thank you.

NI AYE KHIN: I'll do the first part for the historical perspective.

Hi, I'm Ni Khin. And I'll be talking about historical perspective on placebo response in drug trials.

My disclaimer slide. Although I'm currently an employee of Neurocrine Biosciences, part of the presentation today is the work conducted during my tenure with U.S. Food and Drug Administration.

The presentation reflects view of my view and it's not being not quoted with all the organizations that I was affiliated with and currently affiliated.

Let me start with a brief overview of what FDA required for drug approval. FDA regulation defines that there should be substantial evidence, evidence consisting of coming from adequate and well-controlled trial.

The usual interpretation is that it would require two positive randomized controlled clinical trials. However, in terms of drug approval process, we use holistic approach in review of clinical efficacy and safety coming from clinical trials. So in FDA data from both successful and non-successful study, positive and negative studies, as a package when the industry or the drug sponsors submit New Drug Application packages to the agency. And these mainly the efficacy results generally would come from shorter term efficacy data. And safety data will be according to the ICH requirement 1500 patients, three to 600 for six months and at least 100 patients for a year. Generally the maintenance efficacy or also relaxed prevention trials are conducted mostly post approval in the U.S.

So the data that I'm presenting was conducted as kind of a pool analysis from the data that was submitted to agency in terms of in support of New Drug Applications. Why we did that data mining effort. And as you know high rate of placebo response and decline in treatment effect is over time in psychiatry was the main major concern. At the time when we did this analysis if there were increasing trials at clinical trial sites outside the U.S. And we are looking into applicability of such data from non-U.S. sites in the U.S. population.

So we did exploratory analysis of pooled efficacy data from two different psychiatric indication, major depressive disorder and schizophrenia. We have data level coming from trial level and subject level data. And we for depression across the application package, we have Hamilton Depression Rating Scale as the common primary or key secondary efficacy rating scale. And schizophrenia application packages we have PANSS which is Positive and Negative Syndrome Scales.

So we were looking at those two endpoint measures. And then did some exploratory analysis and then summary from these findings. And the processes and challenges experienced in our effort looking into these databases will be shared today.

Let me start with depression trial level data that we looked at. It consisted of 81 RCT short-term trials. So it spans about 25 years. So these are mainly SSRIs and SNRIs, antidepressant. From that 81 short-term control trial, total number of subject was over 20,000 subject, 81% enrolled in U.S. sites. And as you could see here, majority were whites, Caucasian, female. And mean age was around 43 years of age. And baseline HAMD scores were approximately 24. And dropout rate, average dropout rate in these trials was approximately 33%.

We explored treatment effect and trial success rate based on the questions raised about applicability of data from non-U.S. site to the U.S. population. This is the overall results that we published in 2011 paper. We noticed that both placebo and drug group from non-U.S. tended to be larger change from baseline in HAMD-17 total scores than those observed in the U.S.

You can see on the left-hand column non-U.S. site placebo response is approximately 9.5 and U.S. is 8. But drug effect were also larger slightly in non-U.S. sites and U.S. is slightly lower. So if you subtract drug placebo differences, average is about the same for both U.S. -- data coming from both U.S. and non-U.S. sites. So it's about 2.5 points HAMD total difference.

So what we see overall over 25 years of antidepressant trials is that there is increase in highly variable placebo responses across trial. Slight decline in treatment effect moving from approximately three points difference in HAMD total towards two points drug and placebo difference. In trial success rate was slightly lower, 55 versus 50.

And as part of that analysis we also look at any difference in data between fixed and flexible doses. So 95% of the trials that is in the database utilize flexible dosing design regimen. And so placebo responses were quite similar. Treatment effect was slightly larger for flexible doses as compared to fixed dose.

And we pointed out that in our analysis we used data versus -- data coming from the treatment arms versus number of trials as the denominator in the calculation. So slightly higher trial success rate for fixed dose trials, which is 57%, versus flexible dose 50%.

So and some of you may already know that there was an earlier paper published by Arif Khan and his group. A similar database, but it was datasets coming from trial conducted between 1985 to 2000.

And from that analysis it was showing that 61% of the flexible dose studies versus 33 for fixed dose results in terms of success rate. And Khan's use number of treatment arm as the denominator. And if you look at the results, it's a flexible dose is also 60% compared to 31% of fixed dose. However, in our larger database, data included conducted after 2000, that is 2001 to 2008, our findings are in favor of still fixed dose design with success rate around 60% for fixed dose arm, compared to 34% for flexible dose arm. So we think that the more recent trial fixed dose studies, the success rate is likely higher.

So in addition to trial level data, we also look into subject level data from these trials. So for subject level data we initiated with 24 randomized control trial data from -- then we expanded to 45. And the main thing that we were looking at was the – what could we use in terms of responder definition. Do we need a HAMD total cutoff?

So from that analysis we noticed that overall 50% change for baseline is sufficient to define responder status and HAMD total cutoff is not necessary. Whether you use percent change or HAMD total cutoff or both, we would capture more or less the same folks as the responder, median responder status.

And then another item that we looked into was for optimal trial duration. And we -- if you -- from -- generally from eight weeks trials are the ones that would give overall successful trial results. And we looked into whether if we shorten it to six weeks, whether it will get similar results. So it was like somewhere in between that maybe shorten if you could see the two points difference at week six.

And another item that we look into was time to treatment discontinuation instead of change from baseline as the primary efficacy endpoint. And the data support -- not supportive of time to treatment discontinuation as an alternative primary endpoint for drug trials.

So I'm going to cover a little bit about efficacy results from maintenance efficacy trials also known as relapse prevention trials where we usually use randomized withdrawal design.

And they are generally not regulatory requirement in the U.S. to do maintenance efficacy study. But if the agency would see it would be needed, then we'll communicate with the drug sponsor before coming in with the application.

So as you could see on this slide, these longer term maintenance efficacy study generally design as open label treatment for approximately 12 weeks. Once they meet the stable responder status will be randomized into double-blind randomized withdrawal phase to either continue on the drug or the other half will be into placebo. The endpoint generally used is the time to relapse or relapse rate. And we did overall look at trial level data from 15 randomized controlled maintenance, randomized withdrawal trial that was conducted between 1987 and 2012. And you can see demographic disposition is more or less the same for this trial. Average number of subject per study is in the 500. And mean HAMD score at baseline prior to open label is more or less the same. And randomization after they meet responder status to drug and placebo HAMD total score is 9.4.

And the relapse and -- response and relapse criteria used in these studies are varied among studies. And stabilization period is varied. Regardless of that, these are approved based on short-term study. You also see maintenance efficacy based on the results of this study.

This is just the overall slide that shows the duration of open label -- open label response criteria, response rate, double-blind study period, relapse criteria, and different placebo relapse rate and relapse rate and 50% reduction in terms of relapse difference you will see with the drug treatment.

These results were published. And overall I just want to summarize the results saying that almost all the trials are successful. Open label phase, mean treatment response is about 52%. Those meeting responder status going into double-blind randomized withdrawal phase, there is average 50% reduction in relapse rate for drug treatment group as compared to placebo. And in that paper we have side by side comparison of subject level data in terms of relapse survival analysis Kaplan-Meier Curve.

And let me summarize a little bit about schizophrenia trial data. We did have a pool analysis of 32 randomized placebo-controlled short-term clinical trial that was conducted between '91 and 2009. And those are mainly atypical antipsychotics. And this slide shows number of subjects along with mean age and demographic distribution along with the mean baseline PANSS total score.

And we provided the observed increasing placebo response, stable drug response, and declining treatment effect over time in North America region. One thing we would notice was that treatment effect decrease as body weight increased in North America trial patients. And this is FDA also conducted post 2009 period analysis. And this slide shows comparison between pre 2009 trials and post 2009. And you could see that predominantly multiregional clinical trial in recent years dropout rate is higher, slightly higher. But continuing trend of increasing placebo and decreasing treatment effect when you look at in combination of two different pool analysis is that it still persist over 24-year period. Those both level pool data analysis and schizophrenia data analysis is for 25 years period.

So I'm just going to let folks know a little bit about challenges in doing these type of pool analysis is the datasets. Data standard issue. And it was because of the technology in those times' difference. We do not have subject level data trial conducted before 1997 in the database.

And of course always the resources is an issue. And the main point that I would like to bring for everyone's attention is the collaboration, collaboration, collaboration in terms of solving this major issue of placebo response.

I'm going to stop here. And I'll let Dr. Mike Detke continue with this topic from industry perspective. Mike.

MICHAEL DETKE: Thanks, Ni. I'm having problems sharing my screen. I got to make this full screen first. Okay, great. Sorry, minor technical problems. Thanks for the introductions, thanks to NIMH for inviting me to present here.

As Ni said very well, my background is industry. I'll be presenting this from kind of an industry perspective. I've spent 25 years working at a clinical trial site at big pharma, small biotech, and a vendor company all in CNS clinical development, mostly drugs. And I'll -- I'm also a board certified psychiatrist and practiced for about 20 years. I still do medicine part time. And I'll talk about relevant disclosures as they come up during my talk because I have worked in these fields a fair bit.

So that being said, there we go. This is just a high level overview of what I'll talk about. And again, from the industry perspective in contrast to the –

ERIN KING: Your camera is off if you want to turn it on.

MICHAEL DETKE: I will turn it on. My apologies. There we go.

So as I said, I'll be presenting from the industry perspective. And for the most part my definition of placebo response throughout this talk is if the patient got seven points better on placebo and the patients got ten points better on drug, the placebo response is seven points and we'll be focusing on that perspective.

And Tor gave a great overview of many other aspects of understanding placebo. And we'll talk and my esteemed co-presenters will talk more about that, too.

But again, I'll give you the historical perspective. And mostly I'm going to try to go through some data. Some a little older, some a little newer, that of things that have been tried to reduce placebo response and/or improve signal detection, drug placebo separation which especially in a proven effective therapeutic is probably a better way to look at it. And this is just a list of some of the topics I'll cover. I've got a lot of ground to cover, and this won't be exhaustive. But I'll do my best to get through as much of it as possible for you today.

Dr. Khin already talked about designs including the randomized withdrawal design. Important to keep those in mind. I'll briefly mention a couple of other major designs here that are worth keeping in mind.

The crossover design has an advantage that it's much higher statistical power because in -- the ideal way to use this is to use the patients themselves as their own control groups. So you're doing within the subject statistics which make this much more powerful. You do a much more statistically powerful study with far fewer patients.

A couple of important cons are there can be washout effects in the drugs. So pharmacokinetic or even if it's completely washed out, the patient's depression or whatever might have gotten to a better state that might be lingering for some time. And because of these overlap effects there, you can't be totally certain that the baseline of phase two is the same as the baseline of phase one. And that's an important issue. And those overlap effects are important.

But diseases with stable baselines and I think in the CNS space things like adult ADHD could be things that you would consider for this perhaps in proof of concept rather than confirmatory, though. I'll leave that to my colleagues from the FDA.

Sequential parallel design. This has been presented a long time ago and published on much. This is a design where some of the patients get drug in the phase one and others get placebo. They randomize just like a typical parallel arm randomized study. However, in a second phase the placebo nonresponders specifically are then re-randomized to receive placebo or drug. So this has a couple of advantages.

One is that there are two phases from which you can combine the data. And the other is that this second phase enriches for placebo non-responders just like the randomized withdrawal enriches for drug responders. And this has been published on in the literature. This is a slide that hasn't been updated in a while. But the results even back a few years ago were, you know, out of, you know, quite a few trials that have been reported on.

There was a reduction in placebo response in phase two. The drug placebo difference improved. And the p values were better and so forth. So this is an important trial design to know about. Dr. Farchione will talk about I think one example of this having been used recently. It's a little bit hard because you can't really do this within trial comparisons of different trial designs. That's a limitation.

So these are all cross-trial comparisons really. But and there are some advantages and disadvantages. It -- by using patients twice, you might be able to do the trial with somewhat fewer patients, save money, save time. On the other hand, there is two phases so in that sense it might take a little longer. So various pros and cons like anything.

And then I'm going to talk about placebo lead-in. So historically people did single-blind placebo lead-ins where all patients would get placebo for the first week or so blinded to the patient, not to the staff. And then if they had a high placebo response, they would be excluded from the study.

Typically it was about a week and about a 30% placebo response, but it varied. Trivedi & Rush did a great review of this, over a hundred trials as you can see. And little evidence that it really improved -- reduced placebo or improved drug placebo separation. This is some work from my early days earlier in the 2000s at Eli Lilly when I worked on Cymbalta and Duloxetine for about seven years. We did something called a variable duration placebo lead-in where we -- this was the design as it was presented to the patients and to the site personnel that randomization would occur anytime between week -- visits two and four. Which meant they were on placebo for either 0 to one to two weeks. Usually, in fact, they were on for one week.

This has some pros and cons again practically. This -- the placebo lead-in adds a week or two of timeline and cost. The patients, the way this was designed and to maintain the blind, the patients that you, air quotes, throw out for having too high of a placebo response have to be maintained throughout the study which costs money and means that your overall end might need to be higher. So time and money implications.

When we looked at this, Craig Nalstrom, a statistician published from this. And we found that the average effect size did go up pretty substantially, this is going to the effect size. But you also lost some end when you excluded placebo responders. So the frequency of significant differences did not go up substantially in this analysis.

Moving on. Dr. Khin referred to this study by Arif Khan where flexible dose trials did better than fixed dose. I would say that, you know, the database that Dr. Khin presented from the FDA, bigger database, you know, less publication bias and things like that. So I would lean in favor of preferring that. But I would also say that if you focus on my last bullet point, there is clinical intuition about this. And ask yourself the question if you had a case of depression and you could go see a doctor that would only prescribe 20 milligrams of Prozac to every patient or a doctor that would prescribe 20 milligrams and if you're having side effects maybe titrate down, and if you're not having X he might titrate up, you know, which doctor would you rather go to?

So I think on some level it seems to have good faith validity that adjusting the dose to individual patients should lead to better efficacy and better assessment of true tolerability and safety. And that should do a better job than adjusting the dose of placebo. But importantly, because flex dose studies are two arms, one drug with a flexible dose and one placebo. And fixed dose studies are frequently dose-finding studies with, say, one arm of placebo and maybe three arms, 10, 20 and 40 milligrams of drug. So the number of treatment arms is practically, it's confounded with fixed versus flexible dosing. And likewise -- and that may matter. And the percentage randomized to placebo. And again, this is confounded with number of arms.

If you do equal randomization in a two-arm study, you have got a 50% chance of placebo; a four-arm study, you've got a 25% chance of placebo. And again, it makes good base validity, good sense that if your chance of getting placebo is much higher then you might have a higher placebo response rate or the chance of getting active drug is higher.

And that is what Papakostas found in a meta analysis in depression and Mallinckrodt again in a meta analysis of schizophrenia data. So those were all confounded. And they have pros and cons. And you do need to do some dose finding with your drug anyway. So they are all designs that have pros and cons to lead to better outcomes.

Better scales. This is a simple analysis taken from that same paper that did the double-blind placebo lead-in with Mallinckrodt. And we just looked at a pooled set of 22 RCTs. I think these were mostly or all duloxetine studies and depression studies. And the HAMD-17 item scale had an average effect size of about .38. But some of these subscales, which are, you know, five, six, seven or eight items long of items among the 17 in the HAMD. In other words, if you throw out half of the data from the HAMD, you could actually get a better effect size. And so this is something to think about at least in proof of concept. Obviously these subscales would need to be validated for regulatory and other purposes. But good to know that there are different approaches.

And too, if you have a drug that you believe based on earlier clinical data or preclinical data that are more likely to be efficacious in certain domains, symptom domains, that is important, too.

Statistical approaches. This is a little bit dated at this point in time, but there are a lot of important statistical issues to take into account. When I entered the industry, last observation carried forward, LOCF, was the gold standard. There have been a lot of papers published on mixed model repeated measure that protects better against both false positives and false negatives, gives you better effect sizes here. And here almost, you know, 30 or so percent bigger which is pretty substantial. And I'll show you that later. So better protection against false positives and false negatives means we have got more true positives and true negatives which is exactly what we want in therapeutic development.

And I'll talk here now about different implementation strategies during the trial. Central raters and a lot of people use different terminology here. So my terminology for central ratings is when a rater is remote and actually does the assessment. They are asking the questions, they're hearing the answers, they are asking for clarification, they are doing the scoring, etc. And these raters can be more easily blinded to protocol pressures and more easily independent of pressures to meet enrollment and so on and so forth. Note here, I was previously an employee and stockholder and consultant to MedAvante which was one of the companies that pioneered doing the central ratings. So I'm no longer -- I don't have any stock or no financial conflicts of interest now, but I did work with them for a while.

One advantage to centralized ratings on the right is that you can simply use fewer raters which reduces the variance that all of us humans are going to contribute. These people can be trained together more frequently and more consistently. And that can reduce variability, too.

Just some perspective, and Tor presented some nice stuff from other therapeutic areas, too. Is that, you know, in psychiatry, in CNS most of our outcomes are subjective and highly variable and probably need to be improved upon in some ways. Despite that, in other areas where there is probably less inherent variability, they have already standardized the fact that, you know, centralized blinded review or assessments by at least a second or a third person for lots of other types of therapeutics. And these are relatively old guidances from the UMA and FDA mandating this in other therapeutic areas.

So then to get back to the data on centralized ratings, MedAvante was able to conduct about seven studies where they did within study comparisons of site-based ratings and centralized ratings. And across these seven studies, my interpretation, and you can look at the data, are that about five of seven were green. They were clearly -- clearly showed better lower placebo responses or if there was an effective drug, better drug placebo separation with centralized ratings. And two showed pretty equivocal or not impressive differences.

And again, I'm a former employee and consultant to MedAvante. Here is one example, a large GAD study with -- that had escitalopram as an active comparator. And you can see the effect size was about twice as big in HAM-A points. The Cones-D effect size here was about twice. And the chart we put together when I was at MedAvante illustrates that a doubling of the Cone-D effect size means that you can either reduce your sample size by 75% and still have the same statistical power; or you can select a sample size of, say, N of 100 and your power goes up from about 60 to almost 100.

The more important way to read these powers is that your chance of a false negative, your chance of killing your drug when you shouldn't have is 38% with this effect size. And less than 1% with this effect size.

So then there are other approaches than having a central rater really do the assessment remotely. You can review the work, have a third party review the work of the site-based raters. MedAvante, their competitors Verisite, Signed and others all offer these services now and other companies do, too. And I'm not trying to -- and I don't know of any reasons to prefer one versus the other.

So you can review the source documents, audio or video recordings. This looks like it should work. It has good face validity. I've run trials with this. But I'm just not aware of any control data. I haven't seen studies where people have done third-party remote feedback in, say, half the sites or half the raters and not the other half and shown results. If you have those data, please send them to me. I'd love to incorporate those.

But, as I said, it has good face validity. You know, if you're giving people feedback on the quality of their assessment, the raters should do nothing but improve. There is effect called the Hawthorne effect that people behave differently when they know they are being monitored. This should work.

And let me talk a little bit about operations, doing central ratings is pretty burdensome. You have got to coordinate ratings with a rater that's somewhere else maybe in a different time zone and the patient and the site. It's expensive. It's labor intensive. This is less labor intensive because you don't have to review all the recordings. It can be done not in real time. And so it's less burdensome, it's less expensive.

Not clear exactly how efficacious it is, but it has good face validity. Or just replace those human raters with computers. There have been a lot of different groups that have done work on this. And I'm going to jump right into some data.

These are data from -- you'll recognize duloxetine again. And John Grice was one of the early pioneers in this in a company called Healthcare Technology Solutions. And this was done with patient self-report using IVR. So just basically an old fashioned keypad on a phone is good enough to do this. And the patients self-report this. And for those of you that don't know this, separating 30 and 60 milligrams of Duloxetine is really hard. We never really saw this with clinical rating scales.

But patients self-rating using a computer in days saw really nice signal detection and really rapid signal detection. And this is just another example of a different measure, PGI. And again, really impressive separation on these. Or humans are good and computers are good, why not combine the both. And Gary Sachs founded a company called Concordance many years ago. And it's been merged into other companies. And this is part of Signed now. And they showed that if you did a clinician rating and a patient self-rating by computer and compared them, you could learn a lot from the points that were not -- were discordant. And you could learn a lot about both severity ratings but also inclusion/exclusion criteria, diagnosis, things like that. So that's valuable.

Let's talk about professional patients quickly. This is just an anecdote. And I generally stay away from anecdotes, but I found this is really compelling. This subject returned to the site with their unused pills from their pill bottle. Unfortunately, he had a pill bottle from a different trial site, same sponsor and protocol. And this is probably a common problem. This is a phase three program in depression where they had up to 4% duplicate subjects at least in screening. It could be higher. We don't know how big the problem is. But we know it's a kind of a -- it's a tip of the iceberg issue. Because you can look -- you know, there probably aren't too many patients that are bold enough to try to enroll twice at different sites in the same study, but they might enroll sequentially. They might go through multiple screenings until they get in. They might be in different studies by different sponsors for the same or even different indications. Be in a bipolar study this week and a schizophrenia study next month, and a depression study the month after.

And these patients may or may not be compliant with medications and also protocol features. Anecdotal data on subject selection. There are lots of websites out there that will teach you how to be a bad patient in a clinical trial. And I just want to note, not that it's that a bad thing, I love ClinicalTrials.gov, I use it a lot, but any tool can be used for good or bad things, or almost any tool.

And the reason I mention this to you again, as you are posting your trials on ClinicalTrials.gov you want to be transparent enough to share what you need to share, but you might not want to help them too much with specific details of certain inclusion/exclusion criteria that are subjective and can be, for lack of a better word, faked.

The top three of these are all companies that do duplication check for duplicate patients that might be in your study and another study that they have in their database. I've worked with all of them. And worth noting, this is relatively minimally expensive. You just have to get a few demographics on each patient at screening. So also the site and patient burden are pretty minimal.

And AICure is really more of a medication adherence platform. But of course the really bad professional patients don't want to take the medications either. So there is some overlap between professional patients per se and medication adherence. Medication adherence. I'm going to go through the rest of this quickly in the interest of time. Difficult to know with certainty. Not as helpful if done after randomization certainly if you need intent to treat. But pK collection is important. One way to do it is just pK collection. That is a gold standard that tells you that the drug is in the patient's body. I'm going to skip this slide, too.

If half the patients don't take their medicine, you can imagine that the power is very bad. And I did consult with AiCure previously. That's an important disclosure, too. The reason I like AiCure, not so much because I consulted with them, there are many medication adherence platforms out there on the market. This is the only one where I've seen evidence that their platform is consistent with, correlates with, predicts pK values. So if I were you, that's an important question to ask. Then you also have to ask about all of the operational issues, too.

Biomarkers. I mean when we've got biomarkers, they're great. You know, if you've got a PET ligand and you can -- help you narrow down the dose and really demonstrate that you are engaging the target, that's fantastic. This is just an example of PET ligand. This is another biomarker. This is hot off the press, this was presented just a few weeks ago at ASCP. And the idea here is basically taking baseline demographics and putting them all into an AI model to see what predicts placebo response and drug placebo separation.

This is another company that I work with currently so there is that disclosure with as many grains of salt as you believe. We did a blinded analysis of baseline EEGs and identified three clusters in a placebo-controlled Zoloft study.

In the overall study, it just failed to separate. And we identified three distinct clusters, one of which has a huge Cone-C effect size and P value even in a little less than half the population. Another cluster that really weren't responders at all. And a cluster, the third cluster that is less than 20% of the population that had fantastic placebo responders and terrible drug responders.

So this needs more validation like all biomarkers. And I just want to leave this with the point that biomarkers are great as we continue to understand the biology and pathophysiology better. First we are going to have to validate these against the gold standards. And the current gold standards are variable and biased and imperfect. So to close on a relatively optimistic note, this is a red, green, yellow. Green is good. Yellow is questionable. Red is probably not that worth it. My own personal subjective assessment of -- but the takeaway is that a lot of these things can be helpful, especially when fit for purpose with the therapeutic that you are developing, the phase of development, and your strategic goals for that therapeutic.

So I'll end there. Thank you very much for your attention. Look forward to questions and so forth.

TOR WAGER: Great. Thank you, Mike. For time reasons, we're going to go on to our next speaker. But just to let everybody know, there's a Q&A and people are posting questions there. And our panelists can answer questions there in the Q&A panel as well as in the -- during the discussion phase. So keep the questions coming, thank you.

All right. Dr. Farchione, thank you.

Current State of Placebo in Regulatory Trials

TIFFANY FARCHIONE: Thank you. Let me just get this all cued up here. So thanks, everybody, and good afternoon.

As we've already said, my name is Tiffany Farchione, and I'm the Director of the Division of Psychiatry in the Center for Drug Evaluation and Research at the Food and Drug Administration. So because I'm Fed, I have no conflicts to disclose.

I'm going to be providing the regulatory perspective of placebo response in psychiatric trials. So, so far today you've heard a little bit of an historical perspective from Dr. Khin, who is actually my former team leader and peer reviewer. And she showed us that not only do we have a high rate of placebo response in psychiatry trials, but the extent of that problem has actually been increasing over time.

And then Dr. Detke just presented some of the strategies that have been proposed for dealing with this problem. And in some ways they are somewhat limited utility in some examples.

So I'm going to talk a little bit about the importance of placebos for regulatory decision making and give a few examples of placebo response mitigation strategies and registration studies. And then I'll go on and talk a bit about placebo response in other disease areas and end with some thoughts on what may ultimately help us to resolve this issue. All right. So I want to start first by expanding a bit on Dr. Khin's presentation and just quickly presenting some updated data. I saw that there was a question either in the chat or the Q&A about depression studies. And honestly, we don't have too much more from what she presented in depression. And also the things that we've approved more recently have different designs, different lengths of treatment and things like that so it makes it hard to combine them with the existing dataset.

But here we've got figures for schizophrenia and bipolar. And they look a little different from each other because I pulled them from a couple of different presentations. But essentially the data points in each figure represent the change from baseline to endpoint on either the PANNS on the left, or the YMRS on the right in critical trials of atypical antipsychotic medications for the treatment of either schizophrenia or bipolar one disorder.

And the drugs included in these figures are ones for which we have both adult and pediatric data. So on the left you can see that the trend for increasing placebo response over time is also evident in the adolescent trials. And then on the right, we have data from adult and adolescent bipolar one studies, which Dr. Khin didn't present. So there are a few data points in this side, fewer than in schizophrenia. But the trend is less obvious from the dots alone. But if you draw in the trend lines, which are here on the figure, that allows you to see that the same phenomenon is also at play in the bipolar studies.

All right. So let's go back to basics for a minute and talk about why we need placebos in clinical trials in the first place. So simply put, placebo-controlled studies are our bread and butter. And in order to support a marketing claim, companies need to provide substantial evidence of effectiveness for their drugs. Ni went over this a little bit as well. This is generally achieved with two positive adequate and well-controlled clinical studies. And the characteristics of adequate and well-controlled studies are outlined in the Code of Federal Regulations.

So there's seven different characteristics that are listed in CFR, but one of those states that the study has to use a design that permits a valid comparison with a control to provide a quantitative assessment of the drug effect. So more often than not, that's a placebo control.

And they've agreed we just need some way to determine that the drug itself is actually doing something. So if the treatment response in the drug arm is greater than the response in the placebo arm, then that difference is assumed to be evidence of a drug effect. But that may be oversimplifying things just a little bit. It's important to remember that the difference -- the difference between an effect and a response. So the response is the observed result like the change from baseline on a PANSS or a MADRS score. And the drug effect can be one component of that. But adherence to the drug, timing of the assessment, other factors also influence the observed response.

And yes, a portion of the drug response is probably attributable to placebo effect. Same thing with placebo response. Yes, the placebo effect itself is a component of the response observed. But you also have things like the natural history of the disease or regression to the mean or, you know, when we talk about adjunctive treatment, it could be that the other treatment is part of that effect. All of those play a role in the observed response in a study.

So what exactly is it that can account for the placebo response rate in our client's trials? So Dr. Detke went over several of these examples earlier. But let's start with expectancy. And this is a big one. If folks expect to have some benefit from a drug that they're taking, they oftentimes do experience some benefit. The structure of a clinical trial can also contribute to the placebo response. Folks are being seen on a regular basis; they have a caring clinician that they interact with routinely. Those things can in and of themselves be somewhat therapeutic.

The fact that we use subjective outcome assessment is another aspect of this that I want to highlight. Because in psychiatry trials, we can't draw labs or order a scan to ensure that we have the right patients in our trials or to objectively assess their response to the drug. What we have are clinician interviews and patient reported outcomes. And oftentimes these outcome assessments involve a report from a patient that is then being filtered through a clinician's interpretation and then translated into a score on a scale. So there is a lot of room for variability in that.

The distal nature of that assessment from the actual biological underpinnings of the disease can be problematic and it's certainly prone to misinterpretation and to biases also. So again, Dr. Detke also mentioned how enrolling inappropriate participants can impact placebo response. If you have folks in a trial who don't actually belong in the trial, whether that's the professional patients that he kind of finished with, or whether it's folks who just don't quite meet the inclusion criteria or who have been misdiagnosed somewhere along the line, any number of things. That's going to increase the variability in your study and could potentially result in increasing the placebo response. So, of course, there's lots of other factors that can contribute to the placebo response. But because Dr. Detka spent a lot of time on this already, I just wanted to highlight these few skews.

So next I want to talk a little bit about ways in which we could potentially manage the placebo response in clinical trials. First, I want to present one option that we actually have not yet accepted for new drugs in psychiatry, but it's an option that actually takes placebo out of the equation entirely. We have a bunch of approved antidepressants, a bunch of approved antipsychotics. So at this point you might be asking why we can't just do non-inferiority studies and attempt to demonstrate that the new drug is no worse than some approved drug.

So the complicating factor here is that conducting a non-inferiority study requires defining a non-inferiority margin. And in a non-inferiority study, you are trying to show that the amount by which the test drug is inferior to the active control is less than that prespecified non-inferiority margin, which is M1.

And M1 is estimated based on the past performance of the active control. But, unfortunately, because of the secular increase of placebo response over time, we can't really estimate M1. It's a moving target. So even though we have things that have been approved in the past, we don't know that the margin by which the active drug was superior to placebo in the clinical trial that supported its approval is the same margin that would be observed today under similar circumstances. So because we can't set a non-inferiority margin, we can't do non-inferiority trials, at least not for regulatory purposes in psychiatry.

Another strategy that's been employed in a few trials at this point is sequential parallel comparison design. And again, Dr. Detke went over this briefly so you have some idea of the principles behind this already. Now recall that this is a design in which you have two stages. And the first is intended to weed out the placebo responders so that in the second stage the drug placebo difference is amplified --

So there is some statistical concerns with this type of study design related to the relative weights of the two stages and the impact of dropouts. But we have had one application where trials that employed the kind of trial design made it to the New Drug Application stage. And this application was presented at an advisory committee meeting back in November of 2018. So there is publicly available information for me to share even though the application ultimately was not approved.

This was for a fixed-dose combination of Buprenorphine and Samidorphan. So it was intended for the adjunctive treatment of major depressive disorder. Now the figure on the right-hand side was taken directly from the AC briefing book. And it shows diagrams of three studies in which SPCD was employed as part of the clinical trial setting.

The important thing to observe here is that you do in fact have a large placebo response in stage one and a much smaller placebo response in stage two. But what we don't see is the expected amplification of the drug placebo difference in stage two.

So as I said at the advisory committee meeting, either SPCD isn't working or the drug isn't working. So regardless of the outcome here, the important take home point is that we were able to file an application with SPCD in it. We had reached agreement with the applicant on the weights for the two stages and the analyses. And there weren't many dropouts in stage one of the studies. So we were able to overcome two of the big hurdles for this design in this program.

But if we receive another application with SPCD in the future, we're going to have to look at those issues again because they really are trial specific. So we'd advise sponsors to use consistent stage lengths and to reach agreement with us in advance on the primary endpoint and other critical trial features. And even if we reach agreement on all of those things, we're still not going to be able to agree a priori that the study will be acceptable because of some things that we're concerned about will remain open questions until we have that data in hand.

I already mentioned that here there weren't many dropouts in stage one. You don't know that until stage one is done. So even if we do accept the design and the study is positive and all of these issues are resolved labeling is still going to be super complicated if you have an SPCD.

[AUDIO INTERRUPTION] end up writing a label for this one.

All right. So moving from complicated to something much more straightforward. This is a table taken from the clinical study section of the valbenazine label. This is the data that supported the approval of valbenazine for the treatment of tardive dyskinesia. The studies that supported this application really provide a good example of one of the strategies to mitigate placebo response that has been, you know, successful. And that's the use of blinded central raters.

In this study, the raters were blinded to treatment assignment and also to visit number. And using the blinded central raters was feasible here because the symptoms of tardive dyskinesia are directly observable and can even be captured on video. So they can be rated by the remote central raters fairly easily.

And then you'll note here that the change from baseline on the AIMS and the placebo arms was basically negligible.

All right. So I think it's also important to bear in mind that this phenomenon of placebo response in clinical trials is not something that's unique to psychiatry. We see it in multiple other areas of medicine. It's ultimately the reason that we have placebo controlled studies in the first place.

We do expect to see some response in a placebo group. Folks get something that they think could be an active drug and, lo and behold, they have some response. It's important, though, if you want to understand that the observed response is, in fact, related to the active treatment that you do show that folks on the investigational drug are doing better than folks on the placebo.

So for the next couple of slides, I'm going to show some examples of what we see in other disease areas and speculate a bit on why the placebo response rate in those trials is higher or lower than what we're used to seeing.

And I'll caveat this by noting that I pulled my examples from the most recent Office of New Drugs annual report, and I haven't done a deep dive to see if other drugs behave similarly or if my speculation here bears out consistently. But with those caveats in mind, I'm also going to try to draw some parallels to circumstances in psychiatry trials.

All right. So the first example I have here is from the clinical study section of labeling for zavegepant, which is an intranasal calcitonin gene related peptide antagonist that's approved for the acute treatment of migraine with or without aura in adults.

The point I want to make with this example is that the endpoint here, pain, is very subjective. So similar to a lot of what we do in psychiatry, the endpoint is relying on patient report of their subjective experience.

Now, in this case, it probably helps somewhat to have a dichotomous endpoint of pain free versus not, rather than asking participants to rate their pain on a Likert scale that would introduce more variability. And honestly, as somebody who gets migraines, I can tell you that pain free is what matters. Like, a little bit of migraine pain is still migraine pain. Like, I don't want to deal with it.

Anyhow, with that kind of subjectivity, it's not too surprising that about 15% of the folks in the placebo group were responders.

Now, if you think back to that slide I showed earlier about contributors to the placebo response, some of this could be placebo effect. Some of it could just be that their migraines were resolving spontaneously within two hours anyways. Regardless, we have a pretty high placebo response rate here.

But we also have a responder rate of almost 24% in the active treatment group and a statistically significant difference on the primary endpoint of pain free at two hours.

On the secondary of relief from the most bothersome symptoms, so things like photophobia, phonophobia, nausea, both the placebo and the active groups had even higher response rates, but again, a significantly higher response in the active treatment group than in placebo.

So this is from the clinical pharmacology section of that same label. And I want to point out that this is very similar to what a lot of our drugs look like in psychiatry. We describe what the drug does at the receptor level, and then we say that the relationship between that action and the clinical effect on depression or schizophrenia or whatever is unknown. And until we have a better understanding of pathophysiology, that's going to continue to be our approach in labeling.

All right. The next example I have comes from the clinical study section of labeling for linaclotide oral capsules. And I have to say, when I'm talking outside of my own disease area, hopefully I'm getting these pronunciations right. But anyways, it's a guanylate cyclase C agonist. The data here supported the irritable bowel syndrome with constipation indication.

And I think this is a really interesting example because we have two different endpoints here. Like our last example, one is a pain endpoint that's likely to be highly responsive to placebo. Again, it's subjective. But unlike the last example, it's not dichotomous. So it requires a bit more interpretation.

The other endpoint is something that's a bit closer to objective. CSBM is complete spontaneous bowel movements. So, clearly, the number of bowel movements is something that can be counted. But the endpoint itself is a little bit of a hybrid because it also involves a subjective report of the sense of completeness of evacuation.

So, interestingly, you see a much higher percentage of placebo subjects meeting the criteria for responder on the fully subjective pain endpoint than you do on the CSBM endpoint.

And I got to tell you, Section 12 of this label is something that I dream about being able to do for psychiatry. We can only aspire to this, frankly, at this point. The language here very clearly lays out the pathway between the action of the drug and the downstream physiologic effects on constipation. And it even presents an animal model to support the drug's effect on pain. So this suggests that the drug acts on some aspect of the underlying pathophysiology of IBS C.

All right. So, so far I started with an example of a trial with a subjective endpoint, then went to something that's a little bit more objectively measurable. Here I'm going to show data from the bimekizumab label and the studies that supported its indication for the treatment of moderate to severe plaque psoriasis in adults.

So bimekizumab is a humanized interleukin 17A and F antagonist. The endpoints in the study were Investigator Global Assessment, which is an overall assessment of psoriasis severity, and the Psoriasis Area and Severity Index. Now, you might think that these things are somewhat subjective because they are investigator assessments and, of course, require some interpretation to get to the score on these scales.

But these are assessments of the size and extent of the psoriasis plaques, things that are directly observable. And both scales have anchors that describe what type of appearance the plaques of a given severity would have. So, you know, it kind of like gives you a framework for how to, you know, rate these different lesions.

So even though these are global assessments and you might think of clear and almost clear as being analogous to something like improved or much improved on a CGI, we're really talking about very different things.

Here, both what the patient is experiencing and what the clinician is observing are things that you can see and measure. You're not asking the patient if the patient feels like their skin is redder, you can see the erythema. And here you can see a much lower rate of placebo response in the studies. When you're directly observing the pathophysiology in question, and it's something that is objective or relatively objectively measurable, you get less placebo response.

All right. And Section 12 of this label isn't quite as definitive as the linaclotide label in terms of directly linking the drug effect to pathophysiology, but it's pretty close. And, again, it's probably a combination of the relatively objective outcome measures and the tight link between drug action and pathophysiology that's contributing to the low placebo response in these trials.

Finally, I want to put up an example that, of course, has been in the news a lot lately. This is from Section 14 of the tirzepatide label, and this is one of the GLP 1 inhibitor drugs that's indicated for chronic weight management as an adjunct to reduced calorie diet and increased physical activity.

Now, there are all sorts of things that can contribute to placebo response in weight management studies. So, for example, the folks who are in these studies are likely to be motivated to lose weight in the first place. They're required to engage in diet and exercise as part of the study. And even though it's difficult, sometimes folks just lose weight.

So even though weight is something that is objectively measurable, there's multiple physiologic and behavioral factors that may contribute to changes in weight. So there's a lot of variability, and it's been traditionally pretty difficult to show improvement in weight loss trials, or at least to show enough improvement that it overcomes the adverse events that are observed in the trials.

Anyways, the primary outcome in these studies was the percent of patients losing at least 5% of their body weight [AUDIO INTERRUPTION]. Now, you'd think that that would be pretty difficult to surpass, but these studies still managed to show a treatment difference because the active treatment works like gangbusters.

So another way to overcome concerns about placebo response is to find something that really has an impressive treatment effect. Then, even if you have a massive placebo response rate, you'll still be able to show a difference. And so far we don't have much of anything with this kind of an effect in psychiatry, unfortunately.

And then again, once again, in Section 12 we have a mechanism of action description that links the drug action directly to the clinical effects. The drug binds to a physiologic regulator of appetite, the person taking the drug eats less. It's pretty straightforward.

All right. So what lessons can we take away from all of this? Ultimately, the point that I want folks to take home from the examples I've shown in psychiatry and in other disease areas is that there are things that we can do to help mitigate the placebo response in our clinical trials. For things like SPCD or other nontraditional study design elements, I would advise sponsors to talk to us early and often. There are still some methodological issues that, you know, need to be overcome, but we're willing to consider SPCD studies as long as we're able to agree on specific aspects of the design and analysis.

Folks can also do things like trying to improve rater training and to mitigate some of the variability that's just inherent in asking human beings to assign a rating to something that is subjective.

Still related to measurement, but maybe more of a medium term than a short term solution, it could be worthwhile to develop better clinical outcome assessments. The scales that we use in clinical trials now have been around a long time. You know, they were mostly expert consensus and, you know, just they're face valid, for sure, and obviously we have precedent for them, but they've been around longer than modern psychometric principles, quite frankly. So developing new ones would potentially be welcome.

Anyways, in terms of other sources of variability, I'd refer back to Dr. Detke's presentation and his comments on the number of sites, enrollment criteria, and so on. Essentially, quality controls on study design and implementation. But ultimately what's really going to be the real game changer here is when we can develop drugs that actually target pathophysiology. That's when we'll finally be able to take some of this variability and subjectivity out of our clinical trials and really get much more objective measures.

In the best of all possible worlds, we would have a much better understanding of pathophysiology of psychiatric disorders. We'd be able to develop drugs that target the pathophysiological underpinnings of our diseases, and we would even be able to define study entry criteria more appropriately because we wouldn't be relying on subjective assessments for diagnosis or inclusion.

We'd be able to get that blood test or get that scan that can tell us that, yes, this is, in fact, what's going on here, and this is a patient who is appropriate for this clinical trial.

And I understand that we're, you know, a long way from that today, but I hope that folks will think of this as an aspirational goal, that our current state of understanding is less of a roadblock and more of a call to action.

And so with that, and recognizing that I am the one thing standing between you and our break, I will just say thank you very much for your attention.

TOR WAGER: Okay, wonderful. Thank you to all of our speakers and panelists in this first session.

Let's take a short break. We have some questions in the chat. More questions are coming in. But we have a break now until 1:50. And so I suggest that it's a short break, but we can get back on track and start then in about seven minutes. Okay? Thank you.

TOR WAGER: Okay. Hi, everybody. It's a short break, but thanks for hanging with us here and coming back after this short break.

Current State of Placebo in Device Trials

TOR WAGER: Our next session is going to be led off by Dr. Holly Lisanby and Zhi De Deng on the current state of placebo effects in device trials, and then we'll go for a series of placebo effects in psychosocial trials, and then, after that, the panel discussion. Dr. Lisanby, thank you.

Sham in device trials: Historical perspectives and lessons learned

SARAH “HOLLY” LISANBY: Thank you, Tor. And so these are my disclosures. And as Tor said, I'm going to be talking about placebo in device trials. And so although up until now in the workshop we've been talking about placebo in drug trials, which are typically given either by mouth or intravenous or intranasal, we're now turning our attention to how you would do a placebo in a device trial.

And that's where we use the term sham. So we blind device trials typically by doing a sham procedure. And the idea of sham is that the mode of application of the device and the ancillary effects that the device elicits are meant to be as closely matched as possible but without having active stimulation of the body or the brain specifically.

Now, one of the challenges in blinding device trials using sham procedures is that one sham does not fit all or even most. And let me explain what I mean by that.

There are a growing range of different devices. Here you see the landscape of neuromodulation devices. On the X axis is how invasive they are and on the Y axis is how focal they are. And they all use different forms of stimulation applied to the head or the body. Some are surgically implanted, others are not. And those are just the devices that directly apply energy to the head or cranial nerves.

But there's another space of devices that deliver audio or visual stimuli to affect brain activity indirectly, and these include prescription digital therapeutics and neurofeedback devices.

Now, even within one modality of device, here I'm going to use transcranial magnetic stimulation, or TMS, as an example. We have a broad range of different TMS devices. Here I'm showing you just a few of them. And while they all use rapidly alternating magnetic fields, they differ in how they apply that to the head.

So this device, for example, uses an iron core figure 8 coil. This device uses an air core figure 8 coil. Now, those are pretty similar in terms of the electric field induced in the brain, but this device uses three different types of coil that are called H coils with different coil windings that stimulate very different parts of the brain and have different ancillary effects.

The device on the left uses an air core figure 8 coil, but it has some additional bells and whistles to it. It uses neuronavigation. So there's a camera in the room and a tracker to be able to navigate the TMS coil to a specific spot in the brain that was identified before treatment on the basis of fMRI. And so there's an additional aspect of this procedure. And also it's given with an accelerated schedule, where ten treatments are given a day, each day, for five days.

Now that brings us to some of these ancillary effects of TMS. One is the intensive provider contact in a high tech environment. And I'm showing you here just a few pictures from our lab. And this is intensive contact. It can range from either one session a day for six weeks to ten sessions a day over five days. And this really highlights the importance of blinding, not just for the patient, but also the coil operator and the raters.

Now, there are also sensory components to TMS. It makes a clicking noise, which is induced by the vibration of the coil within the casing. And this is quite loud. Even with earplugs, you can't mask the bone conduction of the sound. And so that, in addition to the sound, which can it also can induce scalp sensations. And these sensations can range from just feeling a tapping on your head to feeling something that's a scalp discomfort, even to scalp pain.

And the TMS can also evoke movements. So if you're even if you're not over the motor cortex, if you're over the frontal cortex, which is for depression treatment, this can cause movement in the face or the jaw, which can be from directly stimulating scalp muscles, facial nerves, or cranial nerves.

You can also, depending on the shape of the coil, get some evoked movement from the motor cortex. And this is more common with the more diffuse coils, such as the H coil configurations.

Now, not only are these ancillary effects important for blinding of clinical trials, they also represent important confounds for physiological studies that we do with TMS, where we want to understand use TMS to probe brain function, such as coupling TMS with EEG to study evoked potentials or coupling TMS with fMRI.

Now, sham TMS has evolved over the years. I'm showing you in the center of this photograph active TMS, and in the corners are four different types of early forms of sham TMS, which were called coil tilt TMS configurations, where you tilt the coil off the head so that the magnetic field is sort of grazing the scalp. You get some sensation, you get the noise, but you're trying to not stimulate the brain.

Now, while this coil tilt sham does induce some scalp stimulation and clicking, it lacks operator blinding. But even worse than that, what we showed from intracerebral recordings of the electric field induced in the brain by these different forms of a coil tilt sham in non human primates is that compared to active TMS, which is the top line, one of these four sham coil tilt configurations was almost 75% strength of active TMS. And that's the second line from the top with the black circles.

And so some forms of these coil tilt shams were actually biologically active. And that represents a confound when you're trying to study the older literature, trying to look at, do meta analyses of TMS clinical effects.

The next evolution in the step of sham TMS was shielding. And for example, figure 8 coils could have a metal shield between the coil and the head that blocked the flow of the magnetic field. And here, this E shield has both the magnetic shield as well as a printed circuit board on top of the coil that was meant to be fired antiphase with the TMS in order to try to cancel out the magnetic field at the surface of the head.

These types of approaches look and sound like active TMS, and they provide operator masking. However and they're biologically inactive. However, they don't feel like active TMS. Here you're looking at subjective ratings of scalp pain, muscle twitch, and facial pain with active TMS in the red and sham in the black. So there's not appropriate masking or matching of these ancillary effects.

But that sham, the E shield sham was used in the pivotal trial for depression in adults. And that pivotal trial missed its primary endpoint, which is shown here in the yellow box, where active TMS is in the blue line and sham is in the gray line.

Ultimately, TMS became FDA cleared in 2008 for a limited indication based on this post hoc analysis, which I'm showing you here, where about half of the patients in the pivotal trial who had failed only one antidepressant medication in the current episode showed a significant separation between active in the black line and sham in the gray line. However, those who had more failed trials in the current episode, from two to four, did not separate between active and sham.

Subsequently, the label was expanded and CMS coverage determinations have been provided, but that was on the basis of additional evidence, which came from additional randomized controlled trials as well as open label experience and literature reviews.

Now, that same sham has been used in a pivotal trial for TMS for adolescent depression, which also failed its primary endpoint and failed to separate active from sham. Here you see the antidepressant scores on the Y axis with active TMS in the blue and sham in the red, and they were indistinguishable.

And the sham is described in the paper, as I'm showing you here in the quote, and this is another one of these metal shield or E shield shams that did not provide scalp stimulation.

Now, ultimately, FDA did clear TMS down to the age of 15 on the basis of retrospective analysis of real world data that were derived from a registry of over a thousand adolescents over a span of 15 years, all of whom were obviously receiving off label treatment, as well as a literature review. And the status of insurance coverage is to be determined.

The next step in the evolution of sham TMS was scalp stimulation, and that's what we used in the OPT TMS trial of almost 200 patients. And this was the first study to use scalp stimulation. And you see those little patches on her forehead. Those are electrodes through which we administered weak electrical stimulation to the scalp along with auditory masking in order to better mimic the ancillary effects of TMS.

And here you can see the ratings of scalp discomfort and headache were similar between active TMS in the red and this scalp stimulation sham in the black.

This, we did assess the integrity of the blind in the OPT TMS trial, and we found that the blind was preserved, very low percentage of extremely confident correct responses. And we found a separation between active and sham in this study with a 14% remission with active and 5% remission with sham. That was statistically significant.

Shams in the modern era have kept this idea of scalp stimulation and auditory masking, but they come in different versions that are now available as turnkey systems. For example, this sham, which has an active magnetic stimulation on one side of the coil and no stimulation on the other side, but the sides are identical in appearance, and this comes along with an adjustable output for electrical stimulation of the scalp, which is synchronous with the TMS pulses that's built into the system.

Now I'm going to shift from TMS to a different form of stimulation, transcranial direct current stimulation, or tDCS. This is from one of the randomized controlled trials that we conducted of active versus sham tDCS for depression in 130 patients, which failed its primary endpoint.

Now, I'm showing you the depression response on the Y axis for unipolar patients on the left and bipolar patients on the right. And although we did not find active tDCS to be better than sham, we found something curious, which was that sham was better than active, particularly in the unipolar patients. And that caused us to ask, well, what is going on in our sham tDCS intervention?

Here's what our active intervention looked like. We stimulated at 2.5 milliamps continuously over 30 minutes. The sham, which we thought was biologically innocuous, actually had these brief ramp ups and then ramp downs intermittently during the 30 minutes.

But in addition to that, it had a weak current of .032 milliamps that was continuous throughout the stimulation. We weren't aware of this continuous stimulation, and it begs the question whether this waveform might have had some biological activity. And certainly when you find sham better than active, one has to ask that question.

Now, this question of how to sham tDCS trials has been addressed in the literature. In this study in 2019, they reported that there were a great multiplicity of sham approaches that were being used in the field. And some of these might have biological action.

Now, in 2018 we had conducted an NIMH sponsored workshop and published a report from that workshop in which we urged the field to present the rationale and the effectiveness of sham stimulation when you do studies. And we observed that this is rarely documented. We also encouraged the field to do blinding checklists during the study design, reporting, and assessment of study validity. And we still encourage this. It's still timely.

Now I'm going to move from tDCS to another form of implanted stimulation. So TMS and tDCS are non surgical. Now we're dealing with a surgical implanted device, vagus nerve stimulation.

So it's surgically implanted pulse generator, and sham is done by implanting the device but not turning it on. The pivotal trial of VNS for depression failed its primary endpoint, which is shown in the yellow box here. But it was subsequently FDA cleared based on a non randomized open label comparison with treatment as usual, as you see here. Insurance coverage was frequently denied, which limited utilization.

More recently, there was a study called the RECOVER trial, which stands for randomized controlled blinded trial, to demonstrate the safety and effectiveness of VNS as an adjunctive therapy versus no stimulation control.

This RECOVER study was designed in accordance with the CMS coverage with evidence determination decision memo. The study is not yet published, to my knowledge, but according to a press release from the company that sponsored it, after one year of active VNS versus sham, which was implantation but not being turned on, this study failed its primary endpoint.

And I'm quoting here from the press release that it failed due to a strong response in the sham group, which they said was unforeseen in the study design. And I would say that we might have foreseen this based on the original pivotal trial, which also failed to differentiate active versus sham.

Now I'm going to move to deep brain stimulation. And this is the randomized controlled trial that we conducted on bilateral subcallosal cingulate DBS for depression. Sham was done by implanting but not turning it on. And this study, in a futility analysis, failed to differentiate between active and sham. So you can see this has been a recurring theme in the studies that I've shown you.

Now, there's some specific challenges to blinding DBS trials. By the time you get to DBS, you're dealing with a very severely ill, depressed population, and clinical severity may represent some dangers when you try to think about the relapse that may occur from crossover designs, like crossing over from active to sham.

There are unique things that may unblind the study such as battery recharging or batteries that don't need to be recharged that could cue a patient. And also there's a need for rigorous safety protocols to protect patients who are so severely ill during their sham phases due to the risk of clinical worsening.

So, to conclude, sham methodology poses a lot of complex challenges for device trials. One size does not fit all. The interpretation of the literature is complicated by this variability in the sham methodology across studies and across time as the sham approaches have evolved.

Measuring the biological activity of the sham intervention before using it in a clinical trial is important and it is seldom done. And assessing the integrity of the blind is important for patients, operators, and raters. And that's why with sham procedures we need to think about triple blinding, not just double blinding.

And the shortest pathway to regulatory approval, which I gave you in the example of VNS, does not guarantee insurance coverage nor clinical adoption.

Some thoughts about future directions. We could focus on developing next generation active devices that lack these ancillary effects that need to be mimicked by sham. Some examples that you'll hear about from Zhi Deng, who's coming up next, include quiet TMS and controllable pulse TMS. We could conduct studies to validate and characterize the biological actions and expectancy effects of sham interventions. And there's a role for active stimulation of a control brain area as a comparison condition.

These are the members of the Noninvasive Neuromodulation Unit in our lab at NIMH. And I'll just show you the slide that we're recruiting for jobs as well as for patients in our trial. And thank you very much, and let me hand it back to you, Tor.

TOR WAGER: Wonderful. Thank you, Holly. All right. I think we have Zhi up next. So please take it away, Zhi.

Challenges and Strategies in Implementing Effective Sham Stimulation for Noninvasive Brain Stimulation Trials

ZHI DE DENG: I will share screen and maximize it. Good day, everyone. Thanks for having me here today. And for the next few minutes, I will discuss the challenges and strategies in implementing effective sham stimulation for noninvasive brain stimulation trials.

Dr. Lisanby has already gave a very nice overview as to why this topic is crucial as we strive to improve the validity and reliability of our neurostimulation device trials. I'll be discussing in more in depth the physical characterizations, computational modeling, as well as some measurements that we took of various sham strategies and discuss their trade offs in case you are interested in picking or implementing a sham technique or improving one. And I'll be focusing primarily on TMS and tDCS.

Before we proceed, I need to disclose that I am inventor on patents and patent applications owned by various institutions. Some of them are on brain stimulation technology. Additionally, this work is supported in part by the NIMH Intramural Research Program.

So when we talk about ... is this panel in the way? Let me put that aside.

TOR WAGER: It looks good. I don't think we can see it.

ZHI DE DENG: Okay, good. So when we talk about creating a valid sham TMS, Dr. Lisanby has already mentioned that there are several critical elements that we need to consider.

Firstly, the sham should look and sound like the active TMS to ensure a blinding. This means that the visual and auditory cues must be indistinguishable between sham and active conditions.

Secondly, the sham should reproduce the same somatic sensations, such as coil vibrations and scalp nerve and muscle activation. This sensory mimicry is essential to maintain the perception of receiving active stimulation.

And finally, perhaps the more important one, that there should be no active brain stimulation, which means that the electric field induced in the brain should be minimized to avoid any therapeutic effects.

For TMS, there are several categories of ways to implement sham, which are loosely categorized into the coil tilt techniques, two coil configurations, and dedicated sham systems. I'm going to describe each of them in some detail next.

So Dr. Lisanby has already covered the coil tilt technique, and this is one that was pretty popular in the early days of TMS. By angling the coil 45 degrees or 90 degrees relative to the tangential plane of the head, one can minimize the stimulation to the brain. At least they thought so.

It turns out through modeling and also intracranial recordings of induced voltages that some of these coil tilt techniques remain biologically active. Here you see simulations on a spherical head model of various coil manipulations in coil tilt. Up here we have the active figure of 8 stimulation producing a single focus of electric field directly underneath the center of the figure of 8 coil.

When you tilt the coil 45 degrees or 90 degrees, and when you look into the brain, there is considerable residual electric field that is still induced with these coil tilt techniques.

A better way, a very clever way, and this is popularized by some folks in Europe who's doing motor excitability studies, involve two coil configurations. You use two TMS coils that are attached to two different TMS stimulators, and you would position these coils perpendicular to each other, one in the active tangential configuration and one that is 90 degrees on top of the active coil.

And with this technique, the advantage is that you can interleave active and sham TMS pulses in the same protocol because you are dealing with two different TMS stimulators. So in active mode, you would simply fire the coil that is closer to the head, which is tangential in the active configuration. In sham mode, you would simply fire the coil that is on top of the active coil.

However, this technique, like the coil tilt, there is a spacer involved in this perpendicular coil setup. So the field that is induced in the brain is less compared to the 90 degrees coil tilt, but it does also not induce any scalp stimulation. That means that the sensation at the scalp level is decreased and not felt by the participants.

Another implementation involves a sandwich design, also involving two coil setups that are sandwiching a metal shielding plate. In active stimulation mode, one would fire the coil that is closer to the head, and in sham mode one would fire the coil that's further away. And this shield ensures that you have the -- limits the penetration of the magnetic field, resulting in no scalp stimulation as well as no brain stimulation.

The final category of sham systems are these dedicated sham systems manufactured by different companies, the first of which is a reversed current sham. Magstim has an implementation of this concept. In active stimulation, the coil current in the coil is such that there is a same coil current direction underneath the center of the coil, summating the field underneath the center.

In the sham stimulation setup, the coil current in one of the loops is reversed such that at the center of the coil the field is canceled. This effectively creates a larger circular or oval type coil, which is a larger coil that has a lesser field decay, and so when you actually look into the brain, there remains substantial electric field stimulation there.

Another technique that was mentioned earlier is shielding by, again, putting a metal shield or new metal shield underneath the coil. You can effectively block out all of the field penetration, but one would also completely eliminate any scalp stimulation, making the sensation feel different.

Another implementation strategy involves using a spacer and a passive shielding. This is an implementation of the MagVenture coil, for example, using a large block coil, and the coil winding inside that large block is only built into one side of the coil. And so during active stimulation, one would flip the coil such that the active winding is closer to the head. And for sham stimulation, one would flip this coil over such that the passive shielding is closer to the head and the active winding elements are further away from the head.

This shield technique plus the spacer would completely eliminate any brain stimulation, but it also would eliminate any scalp stimulation.

A final coil setup was invented by our lab several years ago, which we called the quadrupole coil. This implementation splits the figure of 8 coil into four loops, and by reversing the coil current direction on the outside loops during sham stimulation, effectively, you may get into a smaller figure of 8 coil. And as we know, with smaller coils, it has a lower field penetration, and therefore the scalp stimulation is reduced as well as the brain stimulation is reduced.

How do all of these different sham stimulation strategies stack up on each other? The criteria we want to achieve is basically 100% scalp stimulation compared to the active electric field. So when we quantify this sham electric field at the scalp, one would like to achieve 100% compared to the active E field in the active configuration.

When it comes to brain stimulation, in sham, E field should be zero. You don't want any electric field induced in the sham condition. And so one would like to maximize this contrast between scalp stimulation and brain stimulation.

But looking across the coil tilt techniques, the two coil configurations and dedicated sham systems, none of these techniques perfectly achieve what we want. Either you have no scalp stimulation, but it also has no brain stimulation, or you have residual scalp stimulation and brain stimulation at the same time, confounding clinical trial results.

So these are the primary challenges in implementing sham systems. There is a incomplete mimicry of sensory experience that is the scalp stimulation or that you have too much of this residual, possibly biologically active brain electric field that is induced.

So why don't we take a coil that does not produce any brain stimulation and produce no scalp stimulation and add to it some scalp stimulation back? And this is a proposed technique using concurrent cutaneous electrical stimulation, which was used in some of the early clinical trials of TMS, utilizing two electrodes that are placed relatively close together, approximately one centimeter's edge to edge distance underneath the center of the coil.

And the placement of the electrodes is such that you maintain the current direction induced in the head compared to active TMS. And the current is mostly shunted in the scalp, but a little of it enters the brain.

The early implementations of this technique would use a customized ECT device, and the device would deliver low amplitude square pulses that are synchronized to TMS pulses. In more modern configurations, this electrical stimulation module is incorporated into a dedicated sham coil, for example, such as the MagVenture setup.

There are several ways to use this electrical stimulation. One way is to carefully titrate the stimulus intensity for this electrical stimulation to match the active TMS sensation, or some labs maximize the intensity of the electrical stimulation, and this electrical stimulation would be delivered in both active and sham TMS conditions to entirely mask scalp sensation in both conditions.

Now, there are some problems with this cutaneous electrical stimulation, the first of which is waveform considerations. What is the waveform of these electrical pulses that are accompanying this sham TMS pulses? First of all, the manufacturers specified triangular waveforms with a 200 microsecond rise time and a 2 millisecond fall time.

When we actually make measurements of these current pulses, though, the waveform deviates substantially from this triangular waveform that manufacturers specified in their manual. What we actually measured are these exponential decaying waveforms that has a much longer tail compared to the 2 millisecond fall time of the triangular waveform.

What's more is that if one were to characterize the decay constant of this exponential decay and plot it as a function of the intensity of these pulses, one would find that for pulses that are more intense, you have a shorter decaying constant, and therefore it's more pulsatile. If you reduce the electrical intensity, you would end up with a pulse waveform that is longer and longer. And I'll tell you why that's important a little bit later.

A second feature that is peculiar of this system is that the current amplitude is not linear with the dial setting. That is, if you were to increase the intensity from rotating the dial on the machine, a increase from setting of 1 to 2 is not the same as a setting jump from 8 to a 9, for example.

And the maximum current at maximum stimulator setting is upwards of 6.7 milliamps, which is considerably higher compared to other electrical stimulation such as tDCS, which typically uses 2 milliamps.

There's another issue with this electrical stimulation intensity, which is that this electrical E stim intensity was advertised to scale with TMS intensities. That is, as you dial up the intensity of the TMS pulses, the intensity of the electrical stimulation should also increase.

And this is not the case from our measurement. As you can see here, at two different electrical stimulation intensity settings, as we dial the TMS pulse intensity up from 50% to 90%, the amplitude of these electrical stimulation waveforms, they don't really change.

Why is pulse shape matter? Why do pulse shape matter? This has to do with the strength duration property of the sensory fibers underneath the TMS coil. Sensory fibers are classified in this rudimentary drawing of sensory nerves that I put up here.

There are A beta nerves, which are these larger diameter myelinated nerves. And typically they have faster conduction time, and so they carry information about vibrations, pressures, and touch. A delta nerves are slightly smaller, about one to five microns in diameter, and they typically carry information about sharper pain. And then we have these C fibers that are unmyelinated and they are smaller in diameter. And because of the lower conduction time, they would carry information about burning sensations and thermal pain.

I know this is not a very professional drawing of these nerves, and, of course, when it comes to drawing, I am no Rembrandt, but neither was Picasso.

This is actually a more professional drawing, but the important thing about the different pulse shape is that they preferentially activate different kinds of fibers with different time constants. So one can actually model that using a nerve model, which I have done here, and we can show that the proportional nerve activation is different across different waveforms.

On the left cluster of bars, we see what the profile of the proportional nerve activation is like for various types of TMS waveforms, including biphasic sinusoids, monophasic sinusoids, and controllable pulse width, which are near rectangular pulses.

These TMS waveforms preferentially activate A beta and A delta fibers, contributing to this tapping sensation that you feel with TMS.

But when it comes to electrical stimulation using these exponential decaying waveforms, you see that these waveforms preferentially activate C fibers. Not only that, as you change the intensity of the stimulation from maximum to minimum, you preferentially stimulate more and more of the C fibers. That is, if you decrease the amplitude, the tail here gets longer and longer, and you stimulate more and more of these C fibers, and you create more and more burning sensation and this tingling sensation that sometimes people report with tDCS, for example, which is uncomfortable to some people.

But as you increase the electrical stimulation intensity, yes, the pulses become shorter and it feels more pulsatile, but then the intensity is increased, so now it feels more painful.

And so that does not seem to be a way to achieve a very comfortable setup with this electrical stimulation. And what's more important is it does not feel like TMS, that the profile of these nerve activation is very different from a TMS waveform.

So we did not find any perfect sham. The next order of business is that we look into the clinical literature. Might there be any other stimulation parameters such as intensity or stimulation site or stimulation protocol that are predictive of sham response, something that we can modulate and modify.

So we looked into the literature, and we replicated and extended a previous meta analysis looking at depression trials that are randomized controlled trials of TMS. The average sample size across these trials are 35 subjects. In terms of stimulation protocol, predominantly high frequency stimulation and the second largest group would be low frequency stimulation.

In terms of intensity, we have a mixture of intensity with most protocols administering either 100%, 110% or 120% of motor thresholds. In terms of stimulation site, most of these clinical trials use left dorsolateral prefrontal cortex as the treatment target. That as a single site stimulation combined with bilateral dlPFC account for close to 80% of the clinical trials.

In terms of targeting approach, I was surprised to find that we were still using the scalp based targeting strategy of the five centimeter rule, which uses just measurements on the scalp, five centimeters on the scalp anterior to the motor hotspot. And that's where they determine the location for the left dorsolateral prefrontal cortex.

In terms of sham type, a lot of the earlier studies, as Dr. Lisanby mentioned, uses the coil tilt configuration, either 45 degrees or 90 degrees. And so in this analysis, they still account for majority of the studies, and only about a third of the studies included uses a dedicated sham's coil setup.

Manufacturers, you know, it's a mix. In terms of coil types, they're predominantly a figure of 8 coils. And in terms of the number of sessions that are in these studies, the median is 12 sessions of treatment.

So what did we find? What are the correlates of sham response in these clinical trials? The first thing we found was that the number of sessions is correlated with sham response. So here on the Y axis, we're plotting the percent change from baseline for the primary outcome of the study, typically a depression severity rating. So down is actually good, antidepressant. And here we see a weak correlation between the number of sessions in a typical clinical trial with improved sham stimulation.

And this, you know, over a longer treatment course, participants may develop stronger expectation of improvement, and this continued engagement with the treatment process plus regular clinic visits and interaction with a healthcare team can reinforce these expectations contributing to this sustained and enhanced placebo response, which can also accumulate over time.

The second correlate that we found to be significantly correlated with sham response is active response. So in any given clinical trial, the higher the active response, the higher the sham response. And the correlation between sham and active responses may indicate that the mechanisms driving the placebo effect are also at play in the active treatment response.

This correlation might also reflect any form of intervention. And this finding underscores the importance of effective blinding and management of participants expectations and in account for placebo effects in clinical trial design and interpretation. And the final correlate is effect of time. Something that was also mentioned in relation to pain medication a little bit earlier. So Dr. Wager mentioned earlier sham response seems to be increasing over time. We also observe this effect.

Now this increase in placebo response with drugs is sometimes hypothesized to be associated with societal changes in the attitude towards certain types of treatments and perhaps greater awareness in medical research and increased exposure to healthcare information. And also more advertising in general, particularly post approval of a drug or a device. And all together it can enhance participants' expectations and belief in the efficacy of certain types of treatments contributing to stronger placebo response.

Here we see the same thing with devices. There are also other interpretations of this increased placebo response. Perhaps the demographics of the characteristics of the participants in clinical trials might have changed over time. Perhaps participants today are more health conscious, they are more proactive and engage in healthcare, leading to stronger expectations of treatment options.

It could also be that sham response -- sham devices and procedures are becoming more realistic. Changing from the earlier coil till techniques and to now more dedicated sham systems that can enhance the belief that one is receiving an active treatment. The good news, though, is that active response is also increasing, although not quite at the same rate. Active response may be increasing over the years as well, likely attributed to improvements in dosing and targeting techniques.

Speaking of similarities between drugs and devices and their placebo response, there are also some key differences. A study was published last year in Neuromodulation pointing out the differential placebo responses between neurostimulation techniques and pharmacotherapy in late life depression. The time course of this sham placebo response is different between sham RTMS and placebo pills. Specifically at the four-week time point, participants receiving sham RTMS showed a significantly greater reduction in their Hamilton Depression Rating Scale compared to those receiving placebo pills. And this suggest a stronger early placebo response to neurostimulation compared to pharmacotherapy.

But when we look at 12 weeks, the placebo response for drugs start to catch up. And by the end of the twelve -- at the end of the trial at 12 weeks there are no significant statistical difference between the placebo pill response and the sham TMS response. This is important to consider if we're designing clinical trials to compare drugs versus devices, for example.

So we must take care of -- think about when to assess primary outcome and also employ statistical techniques to account for this time-dependent placebo effect.

Touching on TDCS for a second. We don't really have a lot of work on TDCS. Typical sham protocols in TDCS is implemented by changing the time, the temporal waveform of the stimulation, by ramping up during the beginning phase of the stimulation, and sometimes a ramp up/ramp down towards the end of the stimulation to give a transient sense of the brain is being stimulated. There are some protocols that maintained a constant low intensity as shown in Dr. Lisanby's slides that are these microamp stimulation which may or may not be biologically active and that may confound results of clinical trials.

NIMH Staff: Dr. De, I'm sorry, but we are going to need to wrap up to give enough time for our following speakers.

ZHI-DE DENG: Okay, wrap up. Sure. Sure. Final slides. And we're just going to be talking about the -- some of the determinants of sham response in TDCS trials. There seems to be a large sham effect. And there are some protocols that has better blinding compared to the others. And there are certain electrode placement that has lower sham response and that again, similar to TMS, the sham response in TDCS is correlated with the active TDCS response.

With that, I think I will skip the rest of this talk and, you know, allow questions if you have any.

TOR WAGER: Okay. Thank you. Great. Well, keep putting the questions in the chat. And for our panelists, please keep answering them as you can.

We'll move on to the next session right now which is going to cover placebo effects in psychosocial trials and interpersonal interactions.

So our two speakers are Winfried Rief and Lauren Atlas. I believe, Winfried, you are going to go first so please take it away.

Current State of Placebo in Psychosocial Trials

WINFRIED RIEF: Thank you. First, greetings from Germany. And I'm pleased to be invited to this exciting conference.

I was asked to talk about placebo effects in psychosocial trials. And this is certainly a quite critical question whether we can really apply the placebo construct to treatments on psychological therapies and trials in psychological therapies.

So I want to just try to highlight why this is complicated to transfer this concept to psychological treatments. But then I will dive into details how placebo mechanisms might apply and how we might be able to control them in psychological treatments.

So what is the problem? The problem is about the definition of psychological treatments. They're designed studies that utilize psychological mechanisms to treat clinical conditions. But if we consider the definition of placebo effects in medicine, this is pretty similar or highly overlapping with the definition of psychological treatments themselves.

So the impact of psychological and contact factors are typically considered the placebo mechanisms in medical interventions. So we can switch to other attempts either to define placebo mechanisms. But then we need the concept of what are specific, what are unspecific mechanisms. And this is quite difficult to define if we use psychological interventions because we don't have this very clear ingredient as we have in drug trials.

And the novel definition define placebo mechanisms as mechanisms of conditioning and expectation. But this is already a definition of psychological interventions.

And, as you know, CBT started with the concept of using learning mechanisms to improve clinical conditions. So there is an overlap in the definition what placebo mechanisms are and what psychological treatments are. And therefore it's quite difficult to disentangle the effects.

To provide more insight, I reanalyzed a meta analysis of Stephen Hoffman's group on depression and anxiety trials because they only included placebo-controlled trials on psychological interventions. For some of these trials, they were able to have some placebo-proof conditions if they also integrated some psychoactive drug arms. But most of the trials used arms that used some psycho education parts, information about the control or some supported therapies which means just to reflect emotional well being and to support emotional well being.

But some other trials used interventions that are known to be effective such as interpersonal psychotherapy or cognitive restructuring or GRN therapy. So they used therapies as control conditions that are known to be effective in other conditions. And this shows how difficult it is to define what a good placebo condition is in psychological interventions.

And in this meta analysis, in the first version of it six years ago, the authors defined a good psychological placebo conditions as someone -- as a condition that used an intervention and excludes the specific factor, only including the nonspecific factors. And these mechanisms that are used in the placebo arm should have shown to be non-effective for the treatment under -- for the clinical condition under consideration. And this is already a point that will be pretty hard to define in detail if we develop placebo conditions in psychological treatments.

Another attempt, as was already mentioned by Tor, is to disentangle the variant parts of treatment outcome. And this attempt, this approach is associated with names of like Bruce Wampold or Michael Lambert and others. And I show here the results of Michael Lambert's analysis. And you see that he defines placebo effects as the mere treatment expectation effect and to declare this is about 50% and allocates other parts of the effects to other factors.

We have to be aware that this kind of variants disentangling analysis, this is just about statistical modeling. This is not about causal investigation of factors. And a second shortcoming of it is also it does not consider the actions of these factors. And therefore the insight that we get from this kind of analysis is only limited.

But coming back to psychological treatments, we can say that patient's expectations are powerful predicters of outcome, as we know from medical interventions already. Here is data from a psychological treatment study on chronic pain conditions which shows that we find response rates of 35-36%, but only if patients have positive outcome expectations before they start treatment. And those who have negative outcome expectations have much lower success rates like 15%. And the relationship between positive and more negative expectations remains stable over month and years.

So what is the major challenge if we try to define control conditions in psychological treatments? The first point is we're unable to do a real blinding of psychological treatments. At least a psychotherapist should know what he or she is doing. And the placebo group in clinical trials often are different from the active interventions in terms of credibility or as we call it of being on a treatment -- a treatment that is as credible as the active treatment is.

And for some control conditions it's even questioned whether they are kind of nocebo conditions such as standard medical care or waiting list group. If you are randomized to standard medical care or waiting list, you might be disappointed, you don't expect much improvement. While being in the national core group might be even better, you try to do some self-help strategies, for instance. And another aspect is that the nonspecific effects can sometimes switch to become specific effects depending on what your treatment is and what your treatment rationale is.

I'll show one example of one of our studies for this effect. We investigated the treatment expectations in patients undergoing heart surgery. And before they had the heart surgery, we did a few sessions to optimize treatment outcome expectations. That means outcome expectations were moved from being a noise signal of placebo effect to being the target mechanism of our intervention. Like in this case the therapist is working with a patient to develop positive outcome expectations, what happens after they manage to survive the heart surgery.

So we did that with a randomized clinical trial with an expectation optimization in the major group when compared with two control groups. And we were able to show that if we optimize treatment outcome expectations in cardiac, in heart surgery patients, these patients really did better six months after surgery. Standard medical care has little improvement. It's mainly providing survival, which is important enough, no question about that. But where the patients are really feeling better six months after surgery depends on whether they got some psychological preoperative preparation.

And we also used this approach of optimizing expectation to develop complete psychological treatment programs also for patients with depression and with other mental disorders. So let's come to the other part of the placebo mechanisms, the nocebo effect. And I would like to report about nocebo effects in psychological treatments but the major problem is side effects and other effects are only rarely assessed in psychological treatments. This is really a shortcoming.

Here is just a top ten side effects from psychological treatments. Many of them are just increasing conflicts and problems. But some are also about new symptoms that develop. And some of our other studies we even found that symptoms such as suicidal ideation are increasing sometimes for some patients in psychological treatments. So negative side effects are an issue in psychological treatments and we need to assess them and to better understand afterwards whether nocebo effects occur.

How do they develop these treatment expectations, be it either positive or negative? One major effect was already shown in many placebo trials. And that is about pretreatment experience. Here are data of about 300 former psychotherapy users who plan to attend another psychological treatment. And you can see that how much improvement patients expect mainly depends on how much improvement they experienced during the last treatment.

And the same with negative expectations and the same with side effect expectations. Of note, positive clinical outcome expectations are not correlated with negative outcome correlations. That means people can be optimistic and worry at the same time. So a critical role about patient's frequent expectations is the clinician. And we wanted to evaluate the effect of the clinician using an experimental design. Here is our clinician. I will call him Tom. Who is explaining to a critical patient whether psychological treatments can help or not.

And we wanted to modulate this situation and therefore we first brought all our participants in this situation of developing negative treatment outcome expectations. We were quite successful in establishing negative treatment outcome expectations or as you see here, reduction of positive outcome expectations. After that, Tom explained to the patient that psychological treatments are helpful for his or her condition. But Tom changed his behavior. He always used the same information. Psychological treatments are powerful to improve your clinical condition.

But he sometimes was more warm and empathetic. Sometimes he showed no signs of competence. Sometimes both. You can see that it mainly depends on these behavior patterns of the therapist whether the information that he wants to transfer really has some action. If the therapist is low in competence and low in warmth, the same information doesn't have any effect while the same information can have a very powerful effect if the therapist shows warmth and competence.

So let me conclude these few insights into our placebo research. The distinction between specific treatment mechanisms and unspecific mechanisms is less clear than in biomedical interventions. But we can still say that expectations also predict outcome in psychological and psychosocial treatments.

And main determinant of treatment expectations are pretreatment experiences, but also the clinician/patient relationship and many other factors that contribute to a development of treatment expectations. Expectations can be an unspecific factor to be controlled for, but they can also be the focus of an intervention and can really boost their treatment effects and therefore they are -- it's really valuable to focus on them.

And, unfortunately, side effect assessments are typically overseen factors in clinical trials. I'll come to this back in a moment. We want to recommend that placebo-controlled trials are needed in psychosocial intervention -- for psychosocial interventions. But it's more difficult to decide what to include into them. The major idea is to exclude the active mechanisms, but this is not that easily to be defined and therefore we need some psychological attention conditions that are credible in our controlled conditions that psychological treatments are compared with.

I would say that we need a variety of trial designs. Maybe if you start with very new interventions, it might be justifiable to start with a waiting list control group or with a standard medical care group. But if you want to learn more about the treatment, you need more control group designs. And there is not one perfect control condition, but you need variations of it. And last, not least, we have a strong emphasis on side effects and adverse events and unwanted events need to be assessed in psychological treatments as well.

Finally, let's make two comments. I think placebo-controlled investigations are developed and have to be developed to better understand the treatment mechanisms. From the patient's view, they are less important. The patients want to know whether -- what the overall efficacy is of a treatment. That means the combination of specific and unspecific effects, the overall package. And we shouldn't lose that out of mind.

And second, all these mechanisms we are talking about, they are not really to be separated one from the other, but they are typically interacting. Expectation effects are interacting with the development of side effects are interacting with the experience of improvement that can go back to the drug or to the psychological treatment.

So, so far from my side, and I'm happy to hand over to Lauren who will continue to talk about this issue.

TOR WAGER: Wonderful. Thank you, Winfried.

Now we have Lauren Atlas.

LAUREN ATLAS: Thank you. So it's really an honor to be wrapping up this first exciting day of this workshop. And to kind of I guess in a way bring you back to some of the themes that Tor highlighted in his introduction.

So I'll be talking about why I think that we as a field would benefit from taking a social neuroscience approach to placebo analgesia and placebo effects more generally. So Tor used the same figure in his introduction to the day. And I think one of the things that I really want to highlight in this is the distinction between intrapersonal factors so things like expectations, learning, history of associations with different treatments and different clinical context. And this really has kind of been the foundation of most studies of how placebo effects works -- work really because it's quite easy to manipulate things like expectations and learning in the lab and understand how those affect clinical outcomes.

But there has been far less work on the interpersonal processes that support placebo. And in some ways I'd like to say this is really where we need to be going as a field because it could be a lot easier to teach clinicians how to enhance patient outcomes rather than sort of being to fold into what a patient brings to the table. Although of course these factors interact and are both important in determining clinical outcomes.

And so the way I like to think about this interplay is really from a social affect of neuroscience standpoint. So the term social neuroscience really has come about over the past couple of decades talking about how we can use neuroscience techniques to understand emotional and interpersonal processes across a variety of domains. And where I think about this in the context of placebo is, first of all, through neuroscience techniques we can understand how placebo effects are mediated, whether that be supporting specific different types of outcomes or more general processes that shape placebo effects across domains.

From an affect and neuroscience standpoint, we can determine whether the mechanisms of different types of placebo are shared or unique. So, for instance, in the context of placebo analgesia we can ask whether placebo affects are really supported by pain-specific mechanisms or are we looking at the same mechanisms that might also be relevant in placebo effects for depression.

And then finally, from a social standpoint we can really isolate what a role is of the social context surrounding treatment. And so I a couple of years back wrote a review kind of looking at placebo effects from this social affect of neuroscience standpoint focusing on the role of expectations, affect and the social context.

Today I'd like to focus first on mechanistic work using neuroscience to understand how placebo effects are mediated. And secondly to address the role of the social context surrounding treatment. Which I think has implications not only for the study of placebo and clinical outcomes but also for reducing health disparities more generally. And I think I do want to say that I think the study of placebo can really point to all of the different features of the psychosocial context that influence clinical outcomes.

So this is why I think there is so much we can take from the study of placebo more generally. So turning first to how placebo effects are mediated. First, throughout the day we've been talking about how expectations associated with treatment outcomes can directly influence clinical outcomes in the form of placebo. And as Tor mentioned, if we not only compare treatment arms to placebo groups to isolate drug effects but instead also include natural history control groups, we can isolate placebo effects on a treatment outcome by controlling for things like regression to the mean.

Now, again this came up earlier, but a meta analysis of clinical trials that compared placebo with no treatment revealed that there was no placebo effect on binary outcomes or objective outcomes. But there was a substantial placebo effect on continuous subjective outcomes and especially in the context of pain. The others concluded that the fact that placebos had no significant effect on objective continuous outcomes suggest that reporting bias may have been a factor in the trials with subjective outcomes.

So the idea here when we talk about kind of our model of placebo, traditionally we think that things like social dynamics, psychosocial context surrounding treatment, cues associated with treatments lead to changes in one's sensory processing or one's bodily state. And based on that one makes a subjective decision about how one is feeling. For instance, a placebo effect in depression might lead to shifts in emotional processing, or a placebo effect in pain would lead to someone reporting less pain. And this is really driven by our report biases.

The idea is that rather than expectations changing that sensory processing, they affect subjective responses directly perhaps by changing our criteria in first calling something painful. So for over two decades now the field has really focused on asking to what extent are these effects mediated by changes in sensory processing?

And placebo effects in pain are a really ideal way for us to ask this question because we can objectively manipulate pain in the lab. So we can use this device called a thermode heated up to different temperatures and measure how much pain it elicits. And the targets of nociceptive signals are well studied, very well known and we know the tracks that transfer this information to the cortex.

And these can be visualized using functional magnetic resonance imaging or fMRI. So we see reliable activation in response to changes to nociceptive stimuli in a network of regions often referred to as the pain matrix including the insulate, dorsal anterior cingulate, thalamus, medial sensory cortex and brainstem and cerebellum.

Now we used machine learning to identify pattern of weights, which we call the neurologic pain signature that is sensitive and specific to pain and can reliably detect whether something is painful or not and which of two conditions is more painful. So this really provides an opportunity to ask when placebos affect pain. So, for instance, if we apply an inert topical treatment to a patient's arm before administering a noxious stimuli that they believe will reduce pain, does this pain reduction come about through changes in pain specific brain mechanisms or do we see shifts in more general mechanisms such as shifts in affect, things like emotion regulation or value-based learning? So maybe people just feel less anxious but there is nothing specifically about pain. This isn't really a problem because this would also mean that what we're learning about might transfer to other domains.

So a couple of years back nearly all labs that use this neuroimaging to study placebo analgesia in the brain combined patient level data. And what we found is that there was a reliable reduction in pain reports during fMRI scanning when people had an analgesic treatment -- or a placebo, sorry, relative to a control treatment that they didn't believe would reduce pain with a moderate to large effect size.

But there was no reliable placebo effects on the NPS. So this suggests that really we're not seeing placebo effects on this kind of best brain-based biomarker of pain. What do we see the placebo effects modulating? Oh, sorry, it's important for me to say that even though we don't see placebo effects on NPS, there are other psychological manipulations such as mindfulness cues that predict different levels of pain or administering treatments that reduce pain both when subjects know they are receiving it or when they believe they are not receiving it. And these all did affect NPS responses. So it is possible for psychological treatments to modulate the NPS, but we didn't see any placebo effect on NPS responses.

We also conducted a meta analysis of placebo analgesia looking at other published studies. And what we found is that there were reliable reductions during pain with placebo administration in the insula, thalamus and dorsal anterior cingulate. Now these regions are indeed targets of those nociceptive pathways that I mentioned. However, these regions are also activated by pretty much any salient stimulus in that MRI scanner as well as by anything involving interoception or a tension to the body.

And so I think an important point for the discussion is to what extent are these mechanisms or any of the principles we've been talking about today unique to pain or depression or any specific clinical endpoint.

When we looked for regions that showed increases with placebo, we saw increases in the ventral medial prefrontal cortex, dorsolateral prefrontal cortex and the striatum; regions that really have been implicated in domain general shifts in affect, things like emotion regulation and learning about valued outcomes.

So in this first half of my talk I demonstrated that placebo effects seem to be mediated by domain general circuits involved in salience, affective value and cognitive control. We did not see any placebo effects on the neurologic pain signature pattern. And this really points to the idea that these placebo mechanisms are unlikely to be specific to pain.

However, you know, there is many different labs working on different mechanisms of placebo. And so I think this is an ongoing question that really demands on further trials and different comparisons within and across participants.

So now I'd like to turn to the second half of my talk addressing the role of the social context surrounding treatment. And I'm going to talk about this in terms of patient's expectations, providers' assessments of patient's pain, and patient pain outcomes themselves.

So we were interested in asking whether patient's perceptions of providers impact pain expectations. And we know from work that Winfried and many others have conducted that indeed placebo responses depend on many different factors in the patient-provider relationship including how a provider treats a patient.

So Ted Kaptchuk and his group showed that a warm provider can lead to reductions in IBS in an open label placebo trial. We just heard data on how a provider's warmth and competence can influence outcomes. And this has also been shown in an experimental context by Ally Klem’s lab. And finally -- and I'll present this briefly at the end of my talk – we also know that a patient's perceived similarity to their provider also influences pain and placebo effects in simulated clinical interactions.

So a former post doc in my lab, Liz Nekka, was interested in studying this by asking not only whether interactions between patient and provider influence pain expectations but also whether our first impressions of our providers, namely in terms of their competence and/or similarity to us influence expectations even without actual interactions.

And the reason Liz wanted to do this is because we know from social psychology that people's first impressions are really important for a lot of different behaviors. So simply looking at people's faces can predict -- and judging competence can predict the outcomes of elections. And this is work that really has been led by Alex Todorov and his group.

So these faces are morphed along a dimension of competence. And so you can kind of see moving from three standard deviations below the mean to three standard deviations above the mean that there are certain features that are sort of associated with competence and dominance and that we use to make judgments about that person's trait. And so Liz asked whether these types of first impressions also influenced expectations about pain and treatment outcomes.

We conducted five studies on -- using Amazon's Mechanical Turk. And the first studies used those morphed faces from Todorov's group. Importantly, these were just male faces in the first two studies. In our third study, we used the same competence dimensions morphed onto either male or female faces.

We conducted another study in which we removed any cues like hair or clothing and just showed the face, the morphed male or female face itself between subjects.

And in the final study we used real individual faces that varied in race and ethnicity and again had between groups a manipulation of sex. On each trial participants first went through a series of trials in which they saw two faces that varied in competence and told us which provider they would prefer for a potential painful medical intervention. And then they were asked to imagine that provider were performing a painful medical procedure on them, how painful would the procedure be. And after the procedure are you more likely to use over the counter or prescription medication assuming that if the procedure is less painful they would assume -- they would expect to be more likely to use over-the-counter medication.

We also asked about similarities, but I won't be focusing on that today. So across all of the studies, so this is chance. This is that first decision, how likely are you to select a more competent face. What we found is that participants chose the more competent looking provider based on those facial features in the first study. We replicated that in the second study. In the third study we found no difference as a function of the features related to competence. In part because people preferred doctors who -- female doctors who looked less competent based on these features.

In the fourth study we used other individual’s ratings of perceived competence and again found that people selected more competent faces. But they also preferred this particularly only in the male faces. And when we used these real individuals, we again found that other people's ratings of competence predicted somebody's likelihood of selecting that person as their provider. And this was strongest when it came to white providers. We found that competence directly influenced pain expectations in all of the studies except for study three. So here this is the association between ratings of competence and pain. And so you see higher competence is associated with less pain across all the studies but study three. And, again, all the studies showed that the stronger the competence, the more likely somebody was to say they would have an over-the-counter prescription treatment in that study. But we found an interaction with sex such that competence predicted over-the-counter treatment only for male participants whereas competent female providers were associated with higher likelihood of having prescription medication rather than over the counter.

Finally, we found that stereotypes for these kind of information about race, ethnicity and gender which we were able to test in the fifth study also impacted pain expectations. So in study five, we found that expectations about pain varied as a function of provider race. We found that people expected the least amount of pain and highest likelihood of over-the-counter medication from the Asian providers relative to all others. And we also found sex differences in the expected medication use.

And finally, when we ran the meta analysis across all the studies, we found that effects of similarity unexpected analgesic use were strongest in white participants. And this is likely to be kind of an end group preference mainly because studies one through four all included white providers. And we found no other effects of the perceived demographics themselves.

Just with the last like three minutes or so. We know that not only do patients' stereotypes impact perceptions of providers, but we also know through studies on health disparities that providers' beliefs also impact assessment of patient's pain. So Peter Mende-Siedlecki who in this area ran beautiful studies looking at how race bias on pain assessment may be mediated through perceptual changes. Peter had black or white male actors depict pain or neutral faces. And he created morphed images ranging from neutral to painful.

And what he found is that white perceivers needed more evidence of a pain expression before labeling pain on black faces relative to white faces. And the more of the difference they had in terms of likelihood of seeing pain on white relative to black faces also predicted prescribing more analgesics to white relative to black targets across a number of studies.

We asked whether we saw similar biases in evaluations of real pain by measuring facial reactions in acute pain in 100 healthy individuals who label rated pain in response to heat, shock or cold water bath. What you can see is people have very different reactions to pain. This is all kind of the same level of pain. But you see differences in expressiveness.

And we're going to be creating a public database that will be available for other researchers to use to study pain assessment in diverse individuals. We had other healthy volunteers view these videos and assess pain. And critically we selected pain so that there were no differences across target race or gender in terms of the pain or its intensity. All the videos we presented were matched. Subjects saw videos and rated whether the target was in pain or not and how intense the pain was.

And what we found is that perceivers were less likely to ascribe pain to black individuals relative to white individuals. So again, black is here in cyan and white is in pink. And the women are with the hash lines and males are solid. And these are all again selected for trials where everybody is feeling the same amount of pain. And this is really driven by a failure to ascribe pain to black male participants when they were experiencing pain. And this was supported by signal detection analysis. We found that these race-based differences in pain assessment correlated with scores on a modern racism scale but did not vary dependent on perceiver race or gender. And we're now doing a study basically looking at how this type of bias might be reduced through learning and instructions. So basically we find that when people are told about a participant's pain after every trial, they are more accurate in judging other people's pain and that whether or not people receive feedback on pain assessment accuracy improves over time as people practice, suggesting we may be able to reduce these pain assessment biases through training and perhaps in clinical samples.

And finally, I just want to acknowledge that in this kind of dyadic interaction, we really ultimately also want to look at the direct interpersonal interactions that shape placebo analgesia. And this has been done by a series of studies of simulated clinical interactions where healthy volunteers are randomly assigned to act as doctor or patient and they administer a placebo to somebody else.

So Andy Chen Chang showed that telling a doctor that a treatment was analgesic affected the patient's pain, and that this was likely to be mediated through nonverbal communication. Liz Losen's lab showed that -- or Liz Losen when she was in Tor's lab showed that the more similarity or trust somebody had for a clinician the lowest pain they experienced. And finally, Steve Anderson, a grad student with Liz Losen showed that racial concordance between the patient and the provider in a placebo context could reduce pain, particularly in black individuals. And this was also associated with reduced physiological outcome.

So just to summarize the second part on the role of the social context surrounding treatment. I've shown you that first impressions shape pain expectations. Stereotypes impact pain expectations and pain assessment. And that concordance can enhance treatment outcomes.

Finally, just to kind of make clear where I think the path forward is from this kind of social affect of neuroscience approach, I believe that further research on how social factors shape clinical outcomes including placebo effects in placebo analgesia can help us improve patient provider interactions, reduce health disparities in general and maximize beneficial patient outcomes. And that we need more work distinguishing between domain specific and domain general mechanisms of placebo in order to isolate general effects of the clinical context versus targeting disease-specific endpoints. And identifying these kind of domain-specific mechanisms and the features of both patients and providers can really help us address the goals of personalized medicine.

So with that, I want to thank the organizers again for the opportunity to present our work. And acknowledge my former post doc, Liz Netfek, my former PhD student, Troy Duline, my current post doc Allie Jao, and mention that we have positions available in my lab. Thank you.

TOR WAGER: All right. Wonderful. Thank you, Lauren. So that concludes the series of presentations for this webinar for today. But we're not done yet.

Now we're moving into a phase where we have a panel discussion. And so it's going to be very exciting. And we'll get a chance to sort of talk about some of your comments you brought up and other things.

So this is moderated by Carolyn Rodriguez and Alexander Talkovsky. So hi, thank you for doing this, and please lead us off.

Panel Discussion

CAROLYN RODRIGUEZ: Yeah, definitely. So it's my pleasure to do this with Alex. My name is Carolyn Rodriguez. I'm a professor at Stanford. And I see there has been a very lively Q&A already, and some of them are being answered. So maybe we'll just popcorn a little bit.

There is one question here which, you know, I think gets at what we have been presenting is a lot of human data. And so maybe it's just worth noting, are studies in animals free of placebo effect? And, Tor, I see you are typing an answer, but I don't know if you wanted to answer that.

TOR WAGER: Sure. Yeah, I just finished typing my answer. But yeah, it's a good discussion point.

I mean I think that one of the first studies of placebo effects was by Hernstein in 1965 in Science called Placebo Effects in the Rat I think it was called. And there's a resurgence, too, of modern neuroscience work on placebo effects in animals. Greg Corder is going to give a talk on this tomorrow as one of the group of investigators doing this.

So long story short, I think that there are conditioned or learned placebo effects. So pharmacological conditioning pairing with a drug cue or conditioning with place cues can change the response patterns of animals as well.

It's difficult to know what animals are expecting. But there is quite a bit of circumstantial evidence or other evidence from other places even from Robert Rescorla years back or from Jeff Schoenbaum that really used clever paradigms to suggest that animals, it's really a lot about the information value and that they are sort of expecting, you know, and predicting a lot more than we might at first assume.

So even in those conditioning paradigms there might be a lot of something very similar to what we call sort of internal or mental model or expectations that are -- that's happening. So that is my first -- others can jump in here and say more.

CAROLYN RODRIGUEZ: Thank you. Yeah, any other panelists -- panelists, feel free to just turn on your videos and we'll be sort of, you know, asking, anybody else want to weigh in on animals and placebo?

Go ahead, Dr. Atlas.

LAUREN ATLAS: I'd be happy to do so. So actually, there is a study I love from a former post doc who worked with me, Anza Lee, during her PhD that -- we haven't really talked about the roles of dopamine and opioids so far today, which is interesting because those often dominate our conversations about mechanisms of placebo. But Anza had a really lovely study in which she showed that dopamine was necessary for learning the association between a context and pain relief while opioids medullary receptor system was necessary for actually experiencing that pain relief. And so that is a really nice kind of disassociation between that learning development of expectation and the actual pain modulation.

So that was a really lovely place where I thought that the preclinical work had some really nice findings for those of us who are doing human studies.

CAROLYN RODRIGUEZ: Wonderful. Thank you. And I think there is still a day two, so stay tuned. There's -- I can see in the agenda there will be more on this.

But a question I think specifically for you was how does Naloxone influence the NPS? So if there's any -- I think you answered it, but if there's any additional things.

LAUREN ATLAS: I think that's a great question. And I actually don't know of any studies that have administered Naloxone and looked at NPS responses.

The Naloxone effects on fMRI responses in placebo, actually I think we may have -- I'll just say a bit of a final jury problem there. There are a lot of studies that haven't found effects. We really need everybody to kind of publish their data.

But I think we've shown that there are studies of opioid -- or there are effects of opioid analgesics. But I don't think we know anything about blocking the opioid system and its effect on the NPS. But that would be really interesting and important so that's a great suggestion and question.

CAROLYN RODRIGUEZ: Yeah, I look forward to it. That's a very, very exciting question.

I'm going to hop over to neuromodulation. Dr. Lisanby and Dr. Deng, I think you guys have already answered a question which I found fascinating about whether when you try and get the motor threshold, what -- like does that unblind people? So I loved your answer and I just wanted you guys to just say it out loud.

SARAH “HOLLLY” LISANBY: Yeah, thank you. I can start. And Zhi might want to comment as well. So as you may know, we individualized the intensity of transcranial magnetic stimulation by determining the motor threshold where we stimulate with single magnetic pulses over the primary motor cortex and measure a muscle twitch in the hand.

And this is real TMS. And we do real TMS for motor threshold determination regardless of whether the person is going to be getting active or sham in order to give them the same level of intensity and so on. And you might think, plausibly speaking, that this might unblind them if then you give them sham RTMS with repetitive pulses. It turns out that single pulses do not cause the same amount of scalp pain or discomfort that repetitive trains of stimulation can cause.

Also, the motor cortex is farther away from the facial muscles and facial nerves so there is less of a noxious effect of stimulating over the motor cortex. And because of these differences it is very -- a common occurrence that people think they are getting active RTMS even when they are assigned to sham.

Maybe Zhi may want to comment.

ZHI-DE DENG: No, I totally agree with that. The different protocols feel very different. So being non-naive to one protocol might not necessarily mean that you break a blind.

CAROLYN RODRIGUEZ: Wonderful, thank you so much. Dr. Deng, always appreciate your humor in your presentations so thank you for that.

We're going to move over -- Dr. Detke, I think you had messaged that you have a couple of slides that may address some of the questions. And particularly Steve Brennan had asked a question about COVID interference. And there was a question about excluding sites with unusual response patterns. So would love to hear more about that.

I think you are on mute, though. We'd love to hear you.

MICHAEL DETKE: There we go. I have one kind of interesting slide on COVID. It kind of doesn't -- it doesn't get directly at the placebo response.

Let me walk you through. It's a weird slide. Because we've been looking at slides all day that like from left to right is changing -- is the duration of the study or the treatment.

This is actually as you can see on the X axis is actual calendar months. And then focus at first on the blue line. The blue line is the ADCS-ADL which is a scale of activities of daily living. And there are actually questions in it about, you know, have you gone to the grocery store recently? Are you able to do that by yourself? Have you gone to, you know, attended doctor's appointments, things like that.

And the reduction from the -- from early 2020 to kind of the peak of the pandemic, this change of like five points or so, this would be kind of the biggest -- this is an Alzheimer's study -- and this would be the biggest drug effect in the history of Alzheimer's. And this changed back even faster of a similar actually slightly larger magnitude. It was also a huge change.

This is pooled drug and placebo patients. So there is nothing in here that tells you about drug effects or not. You can see this ADL was really impacted by the peak of COVID cases. And I'm actually surprised this came out as clean as it did because we had about 30% of our patients were in Europe, Italy, France, Spain. And as you may recall, the peak of cases there was at a different time than the U.S.

But I think the takeaway here is that obviously things like COVID can certainly impact assessment scales. And they are certainly going to impact scales that specifically say hey, have you gone to your doctor's office when you can't go to the doctor's office. Scales like that are going to be really more impacted obviously than, you know, maybe just -- and moods and things could be, too, obviously. That is one piece of data that I know COVID had a whopping effect on at least one scale.

As for the sites over time, there has been a lot that has been talked about and thought about, about, you know, excluding sites with high placebo response, excluding sites with low drug placebo separation. Of course, if you do that post hoc, it's certainly not valid. There's a banned pass approach where you exclude the extreme sites on both ends, high and low placebo response, is a somewhat more valid. But and my understanding from statisticians is that any of those things increase false positives if you are doing it post hoc.

The other thing to think about when you're thinking about site performance is, A, sites change over time. They have different raters, you know, that might be there for ten years or maybe ten months. And maybe the single most important point on this response is realize, you know, the average depression trial, 100 or 150 patients per arm, 80% power to see a separation. And it's really 50% power as Ni Khin has shown and others effectively.

Now imagine you are looking at a clinical trial site. They have ten patients, five per arm. What is the statistical power there? It's close to zero. And this -- so these are some data that my colleague Dave Dubroda at Lily put together a long time ago. Huge database of I think these were Prozac depression studies. And they had the same -- you know, over many studies and many of them went back to the same sites that performed well.

And as you can see here, the same slide, each chart is a site, a site that was in multiple different studies. And their performance over time and HAMD change was no different. This study is another study that just looks at these are different investigative sites in the same trial. And this is a little bit of a build, but you can see that this site and this site have virtually identical drug responses, the yellow bars. Sorry, that's supposed to be a little higher. They have almost identical efficacy response. But this one has a huge placebo response and that one has a tiny placebo response. Which is probably because they only had five or six subjects per site. And if you get just two or three huge placebo responders.

So trying to assess site performance in the context of a single trial is pretty hard just because of the Ns. And then so evaluating performance by sites is challenging. And then excluding them for reasons like high placebo responses is also challenging. So those are just a little bit of context on that.

CAROLYN RODRIGUEZ: Thank you. Yeah, appreciate that. Question for your colleague Dr. Khin, but maybe for everyone, right?

So there is a question that says isn't it difficult to say that a two-point difference on a 52-point scale is clinically significant? So I know a lot of slides we were trying to say this is going to be significant and what is the difference between, you know, these two scales. So at the end of the day we're, you know, wanting to help patients.

And so what can we say about a two-point change in significance?

NI AYE KHIN: So two-point change is the difference between drug and the placebo. So each individual might have ten-point change or 50% change depending on the individual response. And mostly drug approval is based on statistical significance.

So if there is a two-points difference between drug and placebo for, for example, Hamilton Depression Score, that's generally -- that's the approximate total point change between the two groups that most of the drugs get approved. So, of course, statistical significant changes basing -- we base for drug approval. But for in real world, we don't really know what clinically meaningful change or difference, right. So that's still an issue.

So Tiffany might be able to add more on this topic.

TIFFANY FARCHIONE: Yeah, I mean I can add a little bit. So in terms of like the depression studies, again, those were conducted before our sort of what we do now.

Like if we have a new indication, a new endpoint, something like that, we're going to ask companies to give us an a priori definition of clinically meaningful within patient change. And we're looking, like Ni said, at the difference for an individual. Not the difference between the drug and placebo. But what matters to patients. How much change do they need to have.

And then they can have that -- they can power their study to see some amount of difference that they think matters. But ultimately we have them anchor their studies to, you know, things like global assessments of functioning. We have sponsors if they are using new endpoints do qualitative work so that we can understand what that change means on that given scale. There is a lot of additional work that goes into it now. But yeah, it's the within patient change, not the between group changes that ultimately matters the most.

CAROLYN RODRIGUEZ: Thank you so much. I felt like it was worth saying out loud. And, Dr. Farchione, I know you've done a lot of wonderful work. I heard you speak at ACNP about kind of more global measurements of functioning and really thinking about patients more globally, right. You can change a little bit on a scale, but does that translate into life functioning, work function, these are the things that we care about for our patients. So thank you both for that.

I see Dr. Rief wants to weigh in and then Dr. Lisanby.

WINFRIED RIEF: Just a small little point. The more the question has to be asked about the benefit harm ratio. And it is an important issue and very good that the question was asked. If the difference is just two points, we have to compare it with the risk and potential side effects. It's not only that we can focus on the benefits.

TIFFANY FARCHIONE: We always compare it to the risk regardless of the size of that difference.

CAROLYN RODRIGUEZ: All right. Dr. Lisanby.

SARAH “HOLLY”LISANBY: So this is an opportunity to talk about outcome measures.

CAROLYN RODRIGUEZ: Yes.

SARAH “HOLLY”LISANBY: And how sensitive they are to the intervention and also how proximal they are to the intervention with respect to mechanism. These are some points that Dr. Farchione raised in her talk as well. In psychiatry, the degree to which we can have outcome measures that are more proximal to what our intervention does to engage mechanisms, this might help us be able to measure and differentiate active treatment effects versus nonspecific placebo effects.

And this is part of the rationale of the research domain criteria or dot-research platform to try to look at domains of function. To look at them across levels of analysis and have measurements that might not just be a clinical rating scale. It might be a neurocognitive task that's related to the cognitive function that might be the target of a therapy or a physiological measure that might be an intermediate outcome measure.

So I was hoping we might generate some discussion on the panel about regulatory pathways for these other types of outcome measures and how we might think about selecting outcome measures that may be better at differentiating real treatment effects from nonspecific placebo effects.

CAROLYN RODRIGUEZ: Thank you. I see Dr. Wager, I don't know if you had something to add onto Dr. Lisanby's point or if you had a separate question.

TOR WAGER: I would like to add on to that, if I may.

CAROLYN RODRIGUEZ: Okay. Yeah, of course.

TOR WAGER: I think that's a really important question. I'd love to hear people's opinions about it. Especially the FDA, you know, Tiffany's perspective on it.

Because for me to add to that, I just was wondering how strongly the FDA considers pathophysiology in mechanism of action and what counts as mechanism of action. So there are certainly certain pharmacological changes and cellular level changes that obviously seem to matter a lot. But what about fMRI, EEG, other kinds of indirect measures, do they count, have they counted as mechanistic evidence?

TIFFANY FARCHIONE: Yeah, so they haven't counted yet. And in part because we just don't have either so far an EEG, fMRI, we see group differences but those aren't the kinds of things that can help predict something for an individual patient.

It just goes back to the whole point about understanding pathophysiology and being able to, you know, not just describe that this drug works on this receptor but also working on this receptor has that relationship downstream to X, Y, and Z effects. And in a clinically meaningful way.

I think ultimately a lot of the things we do in terms of our biomarker qualification program and things like that, understanding not just that a drug has some action or interacts with some sort of biology but in what way and what kind of information does that give you that can help inform the trial or help inform, you know, your assessment of drug effect. That's also important. We're a long way off from being able to put things like that into a drug label I would say.

SARAH “HOLLY” LISANBY: I certainly agree with Dr. Farchione's comments.

And I would like to talk for a moment about devices. And there might be different -- there are different regulations and different considerations in drug design versus device trial design. And we are already at a stage in the field of devices where individual physiology is on the label. And that is the case with the Saint technology where individual resting state functional connectivity MRI is used to target on each patient basis where to put the TMS coil.

And I would say that we -- the jury is still out about, you know, studies that unpack Saint to show where that individualized targeting is essential or whether it's the accelerated intermittent data burst and the ten treatments a day and so on.

Regardless, it is on the label. It's in the instructions for how to use the product. And so I think that that might be a sign of where things may be going in the future. And when we think about the way focal brain stimulation is administered, whether it's non-invasive or surgically implanted, we're targeting circuits in the brain. And being able to measure the impact of that targeting stimulation on the functioning of that circuit, EEG or fMRI might be the right readout and it might give some evidence.

I think even still, though, those measures which may be useful in identifying treatments and optimizing their dosing, ultimately I understand from my FDA colleagues that we'll still need to demonstrate that intervention, whatever it is, improves the quality of life and the clinical aspect for those patients.

But it may be an important part of getting the treatments to that phase where they could be reviewed by FDA.

CAROLYN RODRIGUEZ: Thank you so much. That's a good point. Anyone else to contribute to that? I don't see any other hands raised.

Maybe I'll pass it to Dr. Talkovsky and see if there are any other questions that you see on the Q&A that we could continue to ask the panel.

ALEXANDER TALKOVSKY: Yeah, there was one that jumped out to me a bit earlier. There was a bit of a discussion about warmth and competence as well as a perceived tradeoff between the two. And also some ideas about manipulating them as experimental variables that I thought was interesting. I saw, Dr. Rief, you had jumped into that discussion, too.

I thought that was an important enough topic that would be worth spending a little bit more time here in the group discussion making sure that everybody sees it. So I'll throw it back to you, Dr. Rief.

If you could maybe even elaborate on the answer you gave in there about warmth and competence and those as experimental variables, too.

WINFRIED RIEF: The major point I want to make is that we have to control these variables. If we don't control them, we risk they are different between the two or three arms in our trials. Then we cannot interpret the results. That means we have to assess it and we have to make sure that they are comparable between the different treatments. But this is something I can really recommend, I think it makes a lot of sense. There are other points I'm not sure what to recommend. Some people suggest limit, minimize warmth and competence to minimize potential placebo effects. This is the point where the tradeoff comes into the game. If we minimize warmth and competence, people are not motivated to participate and they might discontinue treatments and they are not willing to cope with side effects.

But if we maximize warmth and competence, we risk that placebo effect is bolstering everything. So at this level, at this stage I would say let's try to keep it in an average level. But really assess it and make sure that it's comparable between the different treatment arms.

ALEXANDER TALKOVSKY: Dr. Atlas, I see your hand up.

LAUREN ATLAS: Yeah. I love this question because I think it depends what the goal is. So if the goal is to reduce placebo to find the best benefit of the drug, then yes, you know, in clinical trials when people never see the same rater, for instance, that reduces the likelihood of building relationship. And there's all these different kinds of features that if you really want to minimize placebo then we can use these things in that way.

On the other hand, if the goal is to have the best patient outcomes, then I think we want to do the exact opposite and essentially identify exactly how these features improve patient's wellbeing and heighten them. And so I think really that is part of why I think talking about placebo is so fascinating because it both tells us how to improve patient outcomes and then also reduce them in the context of trials. So I think it really depends kind of what context you're talking about.

ALEXANDER TALKOVSKY: Dr. Rief.

WINFRIED RIEF: Yeah, may I just add a point. Because I missed it and Lauren reminded me to that point.

Most of us assume that we have to reduce the placebo effects to maximize the difference between placebo and drug effects. And this is an assumption. This is not something that we really know. That means -- and we have studied -- for instance, have seen studies in antidepressants and SSRI. We know studies for analgesics. If you reduce the placebo mechanisms to minimum then you are not able to show a difference to the drug afterward because the drug effects are reduced.

In other words, a good drug needs some minimum of placebo mechanisms to show its full action. Therefore, the assumption that minimizing placebo mechanisms to increase the difference between placebo and drugs is an assumption that we have to be concerned about that. And maybe for some drugs it's much better to have kind of average amount of placebo mechanisms.

ALEXANDER TALKOVSKY: Dr. Wager, let's go to you. Then I think we have another question that we want to tackle in the chat after you wrap up.

TOR WAGER: Yep, that sounds good. I see it, too. But just to weigh in on this. Because I think this is one of the most important issues to me. And I think Winfried also just wrote a review about this. And there have been a couple of others. Which is that there is always this tendency to want to screen out placebo responders. It doesn't seem to work very well most of the time in clinical trials.

And if you have a synergistic interaction over additive interaction between an active drug element and a placebo factor motivation or expectation, then screening out -- that is when screening out placebo responders also screens out the drug responders.

And so I think there is this opportunity to test this more, to test, you know, jointly the effects of active treatments whether it's neuromodulation or drugs or something else. And factors like expectations or perceived warmth and competence of the care provider.

So I guess I'm wondering if in the neurostimulation world are there many studies like that or any studies like that because they seem to be very separate worlds, right? You either study the device or you study the psychosocial aspects.

SARAH “HOLLY”LISANBY: Well, I can and maybe others can as well. It's a good point. Lauren, your talk was really beautiful. And my take-home point from that is in a device trial even if we're not studying the effect of the device operator, the effect is occurring in the trial.

And so measuring these aspects of the whole context of care I think can help us sort that out. And in order to do that, I think it could be helpful for investigators who are designing device trials to partner with investigators who have that expertise. Also in terms of the expertise, I was listening very carefully to the talks about psychosocial interventions and maybe the ancillary effects of the procedure is like a psychosocial intervention that we might benefit from having mixed methods approaches that pull from both fields to really better understand what we're doing.

And then there are also trials that use drugs and devices together. So being able to have cross-pollination across the fields I think would be very useful both with respect to our selection of measures to test the integrity of the blind as well as looking at expectancy and even measuring anything about the provider which is usually not done I would just say for device studies. We're usually not even reporting anything about the provider or the perceptions of the subject about the context of their care.

CAROLYN RODRIGUEZ: I wanted to also jump in, in terms of, you know, just in terms of topics. For psychedelic assisted therapy, Harriet DeWitt has a very good question here in terms of commenting about special considerations and testing of placebos. This is something that has come up a lot. And Boris Heifets, among others, has, you know, really gotten us to think about different kinds of designs to disguise the effects of ketamine, for example, with general anesthesia. There's other designs. But questions around the space.

So how important is it when you have a very active placebo that can have empathogenic effects or psychedelic effects in terms of the placebo effect?

TIFFANY FARCHIONE: Yeah, I figure I should probably jump in on this one first.

So, you know, I will say that when it comes to the psychedelics whether it's a classic psychedelic like psilocybin or if it's the empathogen or tactogen types like MDMA, blinding is practically impossible. Folks know if they are on active drug or a placebo. And that makes it really challenging to have an adequate and well-controlled study, right?

On the one hand, we still need to have placebo-controlled studies so that we can get a fairly -- as accurate as you can get assessment of safety of the drug. On the other hand, we've really been struggling trying to figure out what is the best design. Trying to add some kind of an active comparator, you know, choosing something that might mimic some aspect of the psychedelic effect without actually having a treatment effect of any kind is next to impossible. People still know. You know, you've talked about anything from niacin or benzos, a little bit of this, a little bit of that. They know. They just know.

So the best that we've come up with so far is asking for at least one placebo-controlled study so we can get a clear idea of safety. And we've suggested trying to use complementary designs. For instance, you know, it is still possible to have a dose response study serve as an adequate and well-controlled study. Then there is no placebo there. If you can see that a lower dose, mid dose, high dose, if there is a linear increase in treatment effect in that kind of a study, that is helpful to us. If we have -- one of the other things we ask for is to have some assessment of, you know, like an unblinding questionnaire. Do you think you got the active drug? Yes or no. Do you think you got placebo?

And then one of the things we're starting to ask for now in addition to that is not just assessment at the end of whether folks thought they were on active drug or not, not just from the patient but also from the raters trying to see. Because a lot of times the raters can figure out what the person was on, too, so that could introduce some bias.

Now we're starting to think about asking for like a pre-dose expectancy questionnaire of some kind. And so even if we can't necessarily control for the unblinding issues and the expectancy and everything, at least we can try to -- we can have more data to assess the impact on the study and use those as maybe, you know, covariants in the analyses. But yeah, we don't have the right answer yet. We are learning as we go and we are learning very rapidly.

CAROLYN RODRIGUEZ: That may be a plug for NIMH to do like another -- this placebo panel is amazing. We could keep going. I see we have nine minutes left. I'm going to pass it back to Dr. Talkovsky.

And but I know Dr. Lisanby and Dr. Wager have their hands up so I'll pass it back to Alex.

ALEXANDER TALKOVSKY: Thank you. Because we're short on time, with apologies, Dr. Lisanby and Dr. Wager, there is a question I want to address from the Q&A box that I saw a couple of our panelists already addressed in text but seems worth bringing up here as a group.

Are we confident that the placebo effect and specific affect are additive and not interactive?

LAUREN ATLAS: So I'll just -- can I -- oh, sorry.

CAROLYN RODRIGUEZ: Dr. Atlas, yes, that was quick. You won the buzzer.

ALEXANDER TALKOVSKY: Yes, start us off.

LAUREN ATLAS: I had already responded and was putting something in the chat kind of addressing the dose in the same context.

So basically one approach for testing additivity is to use the balanced placebo design so people receive drug or control and that is crossed with instructions about drug administration. So basically people receive the drug under open administration and they also receive placebo. And they receive the drug when they believe they are not getting treatment leading to hidden administration.

And this has been tested with nicotine effects on -- so nicotine, caffeine. We've done it in the context of remifentanil. There has been a couple other trials of different analgesics. It was really developed in the context of studies of alcohol.

We found, for instance, that depending on the endpoint, we have different conclusions about additivity. So when it came to pain, we found additive effects on pain. But we found pure drug effects on neurologic pain signature responses during remifentanil regardless of whether people knew they were receiving the drug or not. We found interactions when we looked at effects on intention.

And other groups, Christian’s group, has found interactions when they did the same exact trial but used lidocaine. And then furthermore, this is what I think we were just talking about in the context of doses. If people have unblinding at higher doses then there is going to be less of an effect of the context surrounding it. So expectations could grow with higher drug effects.

So I think that the question of additivity or interactions really may depend on the dose, the specific drug, and the specific endpoint. I don't think we can really conclude that.

And so even though doing balanced placebo designs do require a level of deception, I think there is really an urgent need to kind of understand how expectations combine with drugs to influence outcomes.

So yeah, I'm really glad somebody asked that question.

CAROLYN RODRIGUEZ: Thank you, Dr. Atlas. I just want to acknowledge Dr. Cristina Cusin who is the other cochair for the panel. She's on, and I want to be mindful of the time and make sure that she and Dr. Wager have the final words or thoughts or if you want to give the panelist the thoughts.

But we wanted to just pass it back to you so you have plenty of time to say any of the things that you wanted to say to wrap things up.

CRISTINA CUSIN: I will leave to Tor if he has any concluding remarks. My job will be to summarize the wonderful presentation from today and do a brief overview of the meeting tomorrow. It was amazing.

TOR WAGER: Since we have a few minutes left, I would like to go back to what Holly was going to say. We have about five minutes. I'd love to use that time to continue that conversation.

SARAH “HOLLY”LISANBY: I'm assuming that you're referring to the psychedelic question. I agree there is no perfect answer to that and it's very complicated. And there are different views on how to address it.

One of my concerns is therapist unblinding and the potential impact of therapist unblinding on the therapy that is being administered. And because as we've heard, it's very likely that the patient receiving a psychedelic intervention may be unblinded. So might the therapist because they know what a patient going through psychedelic assisted therapy typically experiences.

And one thought I have about that could be to measure the therapy, record it, quantify adherence to the manual. At least document what is going on in the therapy interaction. That would give you some data that might help you interpret and better understand whether therapist unblinding is impacting the psychosocial aspects of the intervention because we do -- we've heard from the field that the setting and aspects and context of the use of the psychedelic are an important part. So let's measure that, too.

TOR WAGER: It's really interesting. I want to note there is another -- Boris Heifets has put in the chat there is something that is a different take.

There might be more things to discuss about whether it's possible to blind these things in some ways and some diversity of opinions there. But you can see the chat comment and we can think about that.

I have one other question about that which is that to me I understand the unblinding problem and that seems to be something we're all really concerned about. What about what you call a sensitivity analysis type of design which is if you can independently manipulate expectations or context and maybe some of these other kinds of drug manipulations that induce another kind of experience, right, that is not the target drug, then you can see whether the outcomes are sensitive to those things or not.

So for some outcomes, they might -- it might not matter what you think or feel or whether you had a, you know, crazy experience or not. And if it doesn't, then that is ignorable, right? So you can manipulate that independently. You don't have to blind it out of your, you know, main manipulation. Or it might turn out to be that yes, that outcome is very sensitive to those kinds of manipulations. So I was wondering what you think about this kind of design.

TIFFANY FARCHIONE: I'm not quite sure that I followed that entirely.

TOR WAGER: Yeah, it's really like so you have one that is the psychedelic drug and you don't unblind it. But then you do an independent manipulation to try to manipulate the non-specific factors. If it's, you know, having a, you know, sort of unique experience or having a -- yeah, or just treatment expectations.

TIFFANY FARCHIONE: I guess that's the piece I'm not quite understanding because I'm not sure what you would be manipulating and how you would accomplish that.

TOR WAGER: In the simplest way, the expectation piece is simpler because you can induce expectations in other ways as well, right? By, you know, giving people suggestions that it's going to really impact them. Or, for example, a design that we've used is to say okay, everyone is -- you know, if you get this drug it's going to make you, I don't know, you know, it's going to give you these sort of strange experiences. But if it gives you these experiences, that means it's not working for you, that's bad. Another group you say this is a sign that it's working.

So you take the subjective symptoms and give people different instructions that those are going to be either helpful or harmful and see if that matters.

TIFFANY FARCHIONE: Yeah, I mean I think if you are giving different people different instructions now you are introducing a different source of potential variability so that kind of makes me a little bit nervous.

I guess what I would say is that if somebody had, you know, some sort of creative problem solving approach to dealing with this, I'd love to hear about it. I would love to see a proposal and a protocol. I would say it's probably best to do in an exploratory proof of concept way first before trying to implement a bunch of fancy bells and whistles in a pivotal study that would try to support the actual approval of a product.

But again, because we're learning as we go, we do tend to be pretty open to different design ideas here and different strategies. You know, as long as people are being monitored appropriately because that piece we don't really budge on.

CAROLYN RODRIGUEZ: I see we're at time. Maybe give Dr. Lisanby the last word. Maybe just some food for thought is that maybe it would be nice to have a toolkit to help clinical trialists have some considerations about how to minimize placebo effects would be something nice. Wish list.

SARAH “HOLLY” LISANBY: Yeah, and I just wanted to add to that last question that this is part of why we're sponsoring this workshop. We want to hear from you what are the gaps in the field, what research needs to be done.

Because we are interested in developing safe and effective interventions, be they psychosocial, drug, device or some combination.

And in the research studies that we support use placebos or other forms of control. We're interested in hearing from you where the research gaps are. What sort of manipulations like, Tor, you were talking about, manipulating expectation, to figure out how to do that. All of that is really interesting research topics. Whether that is the design of a pivotal trial or not, doesn't necessarily need to be that.

We're interested in mapping that gap space so we can figure out how to be most helpful to the field.

TOR WAGER: That's a great last word. We still have tomorrow to solve it all. Hope you all join us tomorrow. Looking forward to it. Thank you.

(Adjourned)

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August 28, 2024

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Want a job you'll like? Think about more than the pay, expert says

by Taylor McNeil, Tufts University

Work often defines us. The first question many people ask when meeting someone new is "What do you do?" For those working full-time, a huge portion of their waking hours will be spent on the job. But how often do we think about the role work plays in our lives—and the lives of others?

Mary Davis, an economist and associate professor in the Department of Urban and Environmental Policy and Planning, was struck by that question as she began her sabbatical year in the middle of the pandemic. She was driven, she says, to understand "how work interacts with the health and well-being of people who do the jobs."

Health is impacted by more than just risky occupations, she says, like fishing for lobster solo in the North Atlantic. Health is also affected by job stress, autonomy in the workplace, and finding meaning—or not—in work.

Davis covers these and other topics in her new book , "Jobs, Health, and the Meaning of Work." She wrote the book, she says, to "share the lessons with others seeking jobs that will not only provide balance between work and the rest of life, but also stimulate the idea of work as a source of health, longevity, and the full expression of life's meaning."

In it, she highlights stories of individual workers, including herself, describing her first job as a convenience store clerk in rural Florida, where her boss imbued the value of hard work, and her first job out of college as a federal drug cop at airports—which propelled her back to school.

Tufts Now spoke with Davis, who in August began a new position as senior associate vice provost for education at Tufts; she will also keep her appointment in the Department of Urban and Environmental Policy and Planning.

Some people feel defined by their jobs, but many people just see work as a way to pay the bills. They might share the sentiment I once saw on a bumper sticker, which said, "I owe. I owe. It's off to work I go."

Work is universal, but how each of us translates that experience in our lives is different. In the book, I try to emphasize that even in things like the risk factors of jobs, each person handles them very differently. There's no one size that fits all. Something that is health damaging to one person can be health promoting to another.

I have a sister whose mantra is, "I work to my pay." She has a totally different job than I do. My job is creative and entrepreneurial in many ways. As a professor, I've been able to chart my own course and do interesting things. My take on work is that I'm paid to do what I want to do, and her take is she's paid to do what she doesn't want to do.

Has the nature of work changed due to the pandemic?

I think people's expectations for work have changed. There have been generational shifts in how workers view work and their effort. Even though the Great Resignation, when a much higher than average number of Americans quit their jobs starting in early 2021, has subsided, what pushed it is still there. Workers are more likely to change jobs that are dissatisfying to them than they used to.

Another big change is the number of people looking specifically for remote work. I think as a result of the pandemic, they have a better sense of what they want out of their work lives and are more likely to demand it. And employers are responding. Even employers who want more face-to-face time in the workplace are being more flexible and allowing remote work to attract the best employees.

With remote work, I don't think that we'll be going back to the way it was before. Lots of remote workers are never going to go back to an office space, at least in their current job.

Is the change to remote work a good thing?

I think it's a huge shift, and it has pros and cons. As a single parent , I can understand why having that flexibility and being in the home can be very important to work-life balance in some cases.

But in other cases, how you relate to your peers and how the organization fits together is important to meaningful work. Isolation does not promote a sense that work is meaningful, but good relations and a community feeling do.

I think there's an impact on meaningful work that we don't quite understand yet. Distancing people from their peers is likely to have a negative long-term impact on their sense that work promotes their well-being.

In the book, you describe the case of a remote worker being surveilled and so in fear for her job that when she had a heart attack, she didn't seek help until her shift was over, luckily still in time to survive.

There's definitely more surveillance involved in remote work . It is going to be challenging for years to come as employers figure out the pros and cons of making sure people are efficient, balanced against the potential stress and burnout effects of micromanagement and surveillance.

The gig economy is something that has changed working for many people. What are the upsides and downsides?

Lower-wage workers who survive on this style of contract work are more likely to suffer ill health effects from work. But others do those jobs very much by choice, and it's a positive experience. I've met many an Uber driver who enjoys driving around and talking and earning extra money. Those types of workers are benefiting from the gig economy.

Sometimes the gig economy is presented as being uniformly bad and that we need to create protections for all these workers, but in fact, it's mostly the vulnerable workers—often minority and lower-income workers—who need the protection, not all gig workers. This is why legislating the industry has proven to be so tricky. Effective policies to protect gig workers have to account for the often-conflicting needs of very different worker groups.

Can you talk about how the work environment affects people's physical and mental health?

There is a range from long-term chronic health effects to acute effects. If you look at a fisher falling overboard, for example, that's an acute danger. That is what we've always looked at in the past when considering occupational health—hazards and how to reduce them.

But what many workers face nowadays is more often long-term chronic stress and burnout, sometimes from bad bosses, sometimes from bad organizational structures, as well as pay systems that aren't fair or transparent or company values that don't align with the workers' values.

Irregular scheduling has also been shown to have negative health effects. Workers can't tend to their own health with irregular work schedules. On the other hand, there's a lot of evidence to suggest companies and bosses can remedy this type of situation by creating more predictable scheduling.

What's one piece of advice you'd give based on your research about work?

As I looked at my own work life, how I struggled through various situations, I was able to step back and wonder, what exactly is causing stress right now? Is it something that I can control? Is it something that's organizational? Is it something personal? I was able to do that, looking at my own work life, and found ways to change situations, when that was possible.

The more you know your interests and understand what job situation works best for you, the more you will be able to leverage that in the job market to get a better deal in your work life.

Provided by Tufts University

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Undergraduate Research Topics: History, Art, & More. 300+ Good Research
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Unit 2 Finding A Good Research Topic
Research Methods
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113 Great Research Paper Topics · PrepScholar
113 Great Research Paper Topics. One of the hardest parts of writing a research paper can be just finding a good topic to write about. Fortunately we've done the hard work for you and have compiled a list of 113 interesting research paper topics. They've been organized into ten categories and cover a wide range of subjects so you can easily ...
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A strong research topic comprises three important qualities: originality, value and feasibility.. Originality - a good topic explores an original area or takes a novel angle on an existing area of study.; Value - a strong research topic provides value and makes a contribution, either academically or practically.; Feasibility - a good research topic needs to be practical and manageable ...
301+ Research Topic Examples For Students [Updated 2024]
301+ Research Topic Examples For Students [Updated 2024] General / By StatAnalytica / 12th January 2024. Embarking on a research journey is a crucial aspect of academic growth for students. Selecting the right research topic is like choosing the key that unlocks the door to a world of academic exploration and discovery.
55 Research Paper Topics to Jump-Start Your Paper
55 Research Paper Topics to Jump-Start Your Paper. Matt Ellis. Updated on October 9, 2023 Students. Coming up with research paper topics is the first step in writing most papers. While it may seem easy compared to the actual writing, choosing the right research paper topic is nonetheless one of the most important steps.
Good Research Paper Topics You Can Really Use, With ...
Good Research Topic Ideas. Choose one idea from each column in the table below. Create a phrase that combines those ideas. Use this to generate the beginnings of a research topic. Utilize a search engine to explore the phrase, and you may find a good research topic, even with the wildest combination of ideas.
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There are always more interesting topics to research in these areas. Exploring the Origins of the Universe: Big Bang Theory vs. Multiverse Theory. Enhancing Creativity through Neuroscience Research. The Physics of Black Holes: Mysteries and Discoveries. The Future of Space Exploration: Mars Colonization and Beyond.
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Keep reading for our list of 500 vetted research paper topics and our magic formulas for creating your own topic! Of course, if you want help learning to write research papers tailored to your individual needs, check out our one-on-one writing coaching or academic writing workshop.
Top 100 Research Paper Topics: Start Smart
A good research paper topic is the one that is successful and manageable in your particular case. A successful research paper poses an interesting question you can actually answer. Just as important, it poses a question you can answer within the time available. The question should be one that interests you and deserves exploration.
The Ultimate Research Topic Mega List (1000+ Research Topics)
The list provides 1000+ topic ideas across 25 research areas, including: Accounting & finance. Artificial intelligence (AI) and machine learning. Biotech and genetic engineering. Blockchain and crypto. Business, management and leadership. Communication. Cybersecurity.
What Makes a Good Research Topic?
What Makes a Good Research Topic? Before diving into how to choose a research topic, it is important to think about what are some elements of a good research topic. Of course, this will depend specifically on your research project, but a good research topic will always: ... Good topics have more than one side to the issue and cannot be resolved ...
Starting Points
The biggest mistake you can make, however, is choosing a position before you start your research. Instead, the information you consult should inform your position. Researching before choosing a position is also much easier; you will be able to explore all sides of a topic rather than limiting yourself to one.
Research Topics
Research topic is a specific subject or area of interest that a researcher wants to investigate or explore in-depth through research. It is the overarching theme or question that guides a research project and helps to focus the research activities towards a clear objective. ... One of the most important factors to consider when choosing a ...
How To Choose A Research Topic
To recap, the "Big 5" assessment criteria include: Topic originality and novelty. Value and significance. Access to data and equipment. Time requirements. Ethical compliance. Be sure to grab a copy of our free research topic evaluator sheet here to fast-track your topic selection process.
How to Select a Research Topic: A Step-by-Step Guide
Step 2: Brainstorm Your Topics. You aren't doing research at this stage yet. You are only trying to make considerations to determine which topic will suit your research assignment. The brainstorming stage isn't difficult at all. It should take only a couple of hours or a few days depending on how you approach.
Research Topics
A research topic is a well-defined subject the researcher is interested in. Rational thinking and creative techniques are two methods you can use to generate research ideas. Techniques to find good research topics include brainstorming, getting inspiration from your teachers, using relevance trees, doing a literature search or looking inwards.
14 Ways to Find a Topic for Your Research Paper
Review your course materials. Your textbook, syllabus, and class notes can help you find a topic. If you're writing your paper for a class, skim through your course materials to see what sparks your interest. Major academic journals in your field of study might also give you ideas for a topic. [1]
717 Good Research Paper Topics [Updated August 2024 ]
Some examples of common research paper styles include: Argumentative Research Papers. Persuasive Research Papers. Education Research Papers. Analytical Research Papers. Informative Research Papers. Your research essay topic may also need to be related to the specific class you are taking. For example, an economics class may require a business ...
Overview
Select a topic. Choosing an interesting research topic is your first challenge. Here are some tips: Choose a topic that you are interested in! The research process is more relevant if you care about your topic. Narrow your topic to something manageable. If your topic is too broad, you will find too much information and not be able to focus.
How to Choose the Right Research Topic in 5 Easy Steps
2. Narrow Down Your List. Your next step in choosing a research topic is to start narrowing down your brainstorm list. Start the process of elimination. You might want to cross off topics that don't actually fit with the parameters of the projects, have little in the way of sources, or simply don't interest you.
165 Research Paper Topics for Students [2024]
Good research topic ideas should tick a few key boxes to ensure they're both impactful and manageable. Feature: Description; 🔍 Specific and Focused: ... Explore the ever-changing world of media with these fresh and relevant topics. Each one dives into the trends and challenges shaping how we consume and create content today.
How to Choose a Dissertation Topic
Step 1: Check the requirements. Step 2: Choose a broad field of research. Step 3: Look for books and articles. Step 4: Find a niche. Step 5: Consider the type of research. Step 6: Determine the relevance. Step 7: Make sure it's plausible. Step 8: Get your topic approved. Other interesting articles.
61 Interesting Psychology Research Topics (2024)
Examples of systemic racism-related psychology research topics include: Access to mental health resources based on race. The prevalence of BIPOC mental health therapists in a chosen area. The impact of systemic racism on mental health and self-worth. Racism training for mental health workers.
How can I choose a good topic for my research paper?
Here are some things to consider: Make sure your topic meets the assignment requirements. Ask your professor for feedback if you are unsure. Choose a topic that is interesting to you. It may seem obvious, but this will make the research process more fun and engaging for you. Consider the scope of your topic. If your topic is too broad it may be ...
Beginner's Guide to the Research Process: From Topic Selection to
Discover the essential steps of the research process in this beginner's guide. Learn how to choose a research topic, identify gaps in literature, formulate research questions, design your study, and write a compelling research proposal. Perfect for students and researchers at any stage.
Research Guides: Economics JIW
Choosing a topic that can answer an economic research question is challenging. Some tips: Ripped from the headlines rarely makes a good economic paper. ... Topics such as artificial intelligence may make a good policy paper but not a good economic one due to lack of data. Literature Review: Your JIW should use primarily scholarly sources.
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