Exploring underrepresentation in clinical trials

Clinical trials are essential to advancing medical knowledge and improving patient outcomes. According to the National Institutes of Health (NIH), these studies investigate new drugs, combinations of therapies, medical devices, surgical techniques, behavioral changes, and more. All aimed at preventing, detecting, or treating disease and improving quality of life.

Since 1999, over 186,000 clinical trials have been registered in the U.S., reflecting the nation’s robust research activity. Each clinical trial typically follows a four-phase process:

• Phase 1: Tests a drug or treatment on 20 to 80 individuals for safety.
• Phase 2: Expands testing to 100 to 300 people to assess efficacy and side effects.
• Phase 3: Evaluates the treatment in 1,000 to 3,000 participants for broader safety and effectiveness.
• Phase 4: Conducted after FDA approval, focusing on long-term safety and real-world effectiveness.

The diversity gap

Despite the volume and rigor of these trials, participant diversity remains a persistent challenge. In the U.S., white patients—particularly men—have historically composed the majority of clinical trial participants. Women, along with racial and ethnic minorities, have been significantly underrepresented.

Women in clinical trials

In 1977, the FDA issued guidance excluding women of childbearing potential from early-phase trials due to safety concerns, including birth defects linked to thalidomide use in the 1950s and 60s. While intended as a precaution, the policy also limited data on how medications affect women.

This began to change in the 1980s. The NIH introduced a policy in 1986 to include women in federally funded clinical research. By 1993, it became federal law, and the FDA created the Office of Women’s Health in 1994 to further promote women’s inclusion in trials.

Progress has been made, but gaps remain. A 2022 study analyzing four years of clinical trial data found that just 41.2% of participants were women—still short of parity. Notably, women were underrepresented even in trials for conditions that predominantly affect them.

Racial and ethnic barriers

For minority populations, multiple barriers continue to limit participation. These include:

• Limited access to trials in under-resourced healthcare settings
• Language barriers and mistrust of the medical system, often rooted in historical injustices like the Tuskegee Syphilis Study
• Underinsurance and economic constraints
• Logistical challenges, such as traveling to trial sites and taking time off work

These obstacles contribute to selection bias and a lack of generalizability in clinical data. In 2020, the FDA reported that 75% of clinical trial participants were white with minorities comprising only about 30% of the trial participants. A figure that has seen limited progress over the past decade.

Why representation matters

Increasing diversity in clinical trials isn’t just about equity. It’s about better science. Genetic, environmental, and cultural factors can affect how patients respond to medications or therapies. Without inclusive representation, clinical research risks missing these differences, leading to less effective or even harmful treatments for some populations.

Diverse participation allows researchers to:

• Reduce health disparities and build trust in the healthcare system
• Identify group-specific responses or side effects
• Develop more personalized and effective treatments

Moving forward: increasing diversity

The FDA has taken steps to address the issue. In 2020 and 2022, it issued guidance to improve diversity in clinical trials, recommending strategies such as:

1. Broadening eligibility criteria to include more diverse populations
2. Reducing barriers to participation, such as offering flexible trial locations or remote options
3. Enhancing retention in rare disease studies
4. Increasing community outreach and diversifying clinical trial staff

Creating a more inclusive clinical research environment requires intentional design, community engagement, and systemic change. By working to ensure that all populations are represented, we can move toward a future where clinical trials, and the treatments they produce, benefit everyone.

Further reading

• Understanding the disparities: Why Black Americans suffer from higher rates of diabetes
• A shift in language: How healthcare is tackling stigma
• Women and autoimmune diseases: Understanding causes, trends, and treatments
• Women and migraines: Understanding the impact, triggers, and treatment
• Pharmacy deserts: A growing problem in the U.S.

References

• NIH Clinical Research Trials And You. National Institutes of Health.
• Number of clinical trial registrations by location, disease, phase of development, age and sex of trial participants (1999-2024). World Health Organization. December 2024.
• About Thalidomide. The Thalidomide Trust.
• After 60 years, scientists uncover how thalidomide produced birth defects. Dana-Farber Cancer Institute. August 1, 2018.
• Balch, Bridget. Why we know so little about women’s health. Association of American Medical Colleges. March 26, 2024.
• Sosinsky, Alexandra Z., Rich-Edwards, Janet W., Wiley, Aleta, Wright, Kalifa, Spagnolo, Primavera A., and Joffe, Hadine. Enrollment of female participants in United States drug and device phase 1-3 clinical trials between 2016 and 2019. Contemporary Clinical Trials. Volume 115. April 2022.
• Minority Health Month: Why Diversity is Necessary in Clinical Trials. Masonic Cancer Center, Minnesota Cancer Clinical Trials Network. April 18, 2023.
• Boyle, Patrick. Clinical trials seek to fix their lack of racial mix. Association of American Medical Colleges. August 20, 2021.
• Hamel, Lauren M., Penner, Louis A., Albrecht, Terrance L., Heath, Elisabeth, Gwede, Clement K., and Eggly, Susan. Barriers to Clinical Trial Enrollment in Racial and Ethnic Minority Patients With Cancer. Cancer Control. December 2016.
• Fisher, Jill A., and Kalbaugh, Corey A. Challenging Assumptions About Minority Participation in US Clinical Research. American Journal of Public Health. December 2011.
• Kulkarni, Darshan. The Evolution of US FDA Diversity Requirements in Clinical Research. DIA Global Forum. December 2023.

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