Editor’s note: In this article, the author makes note of guidance published in 2024 by the U.S. Food and Drug Administration (FDA) that required pharmaceutical companies to develop a Diversity Action Plan before submitting an investigational new drug (IND) application. However, in late January 2025 — before we were able to publish this piece — the FDA removed that guidance from its website. This move is part of the current federal government-ordered rollback of diversity, equity, and inclusion initiatives across U.S. health agencies.
While the main page detailing the original guidance can no longer be found on the FDA’s website, the original report to Congress can be found here, and the guidance can accessed at Regulations.gov as well on the Federal Register’s site. We have changed our links accordingly.
Medication is a core component of patient care. Most adults regularly take some prescription drugs, and most also agree, according to a 2024 public opinion poll by KFF, that new drug therapies make people’s lives better.
Access to safe and effective medications should be available to all, but equitable access often falls short. Marginalized groups, who often face higher rates of chronic disease, frequently encounter barriers to obtaining medications, such as limited insurance coverage. However, these inequalities often begin long before a drug even reaches the market.
The lack of diversity in clinical trials is a persistent and deeply complex issue—and it continues to influence the safety and effectiveness of newly approved prescription drugs.
Broadening the Definition of Diversity in Clinical Trials
The clinical drug trial process itself dates back to the 1960s, a time when research participants were mostly young, white men. Since then, a patchwork of policy changes has broadened trials to include more women and underrepresented groups. Despite this, new drugs are often not tested on the very people most likely to take them.
“Diversity and inclusion are critical to the success of clinical trials because, without them, we cannot guarantee the generalizability of the results,” says Rafael Veintimilla, M.D., senior director of Clinical Trials Integration and Medical Science Liaison of the University of Wisconsin Clinical Trials Institute.
In this context, diversity goes far beyond simple categories such as age or gender, encompassing a broader and more intricate set of factors that shape trial outcomes.
The National Institute on Minority Health and Health Disparities defines diversity not only as characteristics such as race, ethnicity, age, and gender; including people with different experiences and living conditions is also essential for predicting how a wide range of people will be affected by a studied drug.
“We are all unique in our biology, and having a broader spectrum of participants gives us a more robust set of data to understand a drug’s benefits and risks,” says Dr. Veintimilla. For example, your genetics can affect how quickly your liver processes drugs, explaining why two people taking the same dosage may have different resulting drug blood levels — and different risks of side effects. The more racial and ethnic groups included in initial clinical drug trials, the more likely these variations in response will be found before a drug is approved.
Matching a drug trial population to the groups of people who will likely take the drug after approval is a goal the FDA has been working towards. In 2022, Congress passed a law that instructed the FDA to develop a new plan for achieving meaningful diversity in clinical drug research. The long-awaited FDA guidance was released in mid 2024. [Editor’s note: In January 2025, this guidance was wiped from the FDA’s website due to an executive order dismantling DEI programs within the federal government.]
This guidance required pharmaceutical companies to develop a Diversity Action Plan before submitting an investigational new drug (IND) application to the FDA. This step was to occur before the FDA approved any studies in humans to be done.
However, these reforms, while ambitious in theory, likely fell short in practice, making inequality in clinical trial participation an ongoing reality.
A Historical Look at Diversity Gaps in Clinical Trials
“Historically, 80% of clinical trials were completed on white males, which meant most drugs worked well for white males,” explains Dr. Veintimilla.
This limited focus stemmed from a healthcare system historically shaped by male– and white-centric biases, along with a legacy of exclusion and unequal treatment.
Male bodies have long been the norm in clinical research. For many years, researchers widely believed findings from male-only studies could apply to everyone. The exclusion of women from clinical research was often justified by concerns over potential harm to a fetus during possible pregnancy (and the subsequent threat of legal liability).
Aside from the issue with pregnancy, a more insidious bias lay in the perception that men were “cheaper and easier” to study due to the absence of a menstrual cycle. This same preference extended even to preclinical research, where studies disproportionately focused on male animals and cells.
To understand the historical context of race in healthcare, it’s important to note that white Americans made up about 85% of the U.S. population as recently as the 1980s. Even after segregation officially ended, non-white populations were commonly restricted to living in areas with fewer healthcare resources. This led to “substantial differences” in how non-white minorities received healthcare during much of the 20th century, explains Clyde W. Yancy, M.D., vice dean for Diversity and Inclusion and Chief of Cardiology in the Department of Medicine at Northwestern’s Feinberg School of Medicine in Chicago.
Even when minorities were included in clinical research, it was sometimes under exploitative and deeply unethical circumstances. Some studied populations were knowingly harmed, raising significant ethical concerns. “There have been serious ethical violations in research, particularly against vulnerable populations and those who put trust in researchers only to have their rights violated,” says Dr. Veintimilla.
One of the most infamous examples, he notes, is the Untreated Syphilis Study at Tuskegee, which lasted longer than a generation and involved withholding standard treatments from Black men who were living with syphilis. These participants were misled to believe they were receiving appropriate care.
The post-Civil Rights period in clinical research was largely focused on the “imperfect notion of trying to make amends for egregious behaviors in the past,” explains Dr. Yancy. The legacy of these violations, he adds, continues to cast a long shadow, shaping both the landscape of medical research and the persistent mistrust among communities that were once exploited in its name.
The Current State of Diversity in Clinical Trials
While clinical research has moved beyond its historically narrow scope, diversity today remains uneven, with significant gaps still persisting.
For example, a study of 32,000 drug trial participants in 2020 found significant underrepresentation among all non-white groups compared to the U.S. Census data demographic distribution.
In contrast, clinical trials leading to the FDA approval of 55 new drug entities in 2023 included larger proportions of non-white groups. However, only one in four participants in those trials lived in the United States. (it’s common for drug companies to run trials overseas due to the potential of lower operational costs.)
This raises questions about whether racial diversity in international studies reflects the experiences of non-white populations within the U.S., particularly since race is a social construct that is fluid, shaped by cultural and social contexts.
Compounding the issue, some study sites failed to report information on Hispanic ethnicity, leaving additional gaps in the data. This broad categorization overlooks the significant genetic, cultural, and health differences among Hispanic subgroups, further limiting the usefulness of the data.
To look at whether trial diversity matched people most likely to take the drug being tested, a 2024 study compared the demographics of clinical trial participants with over 150 million patient health records in the U.S. The researchers found significant disparities among race, ethnic groups and sex across trials, but no consistent pattern emerged.
Diversity also varies widely across therapeutic research areas. Cancer, heart disease, Alzheimer’s Disease (some of the leading causes of death in the U.S.) and HIV/AIDS are specific areas that often lack diversity. In cancer research, for instance, a 2020 study found that Black participants accounted for only 2.9% of drug company-sponsored clinical trials.
New FDA Guidelines and Efforts to Improve Diversity
The Diversity Action Plan originally proposed by the FDA required drug companies to include the following information in their Investigational New Drug (IND) applications:
- The trial design and target participant demographics, including goals for race, ethnicity, sex, age, and other factors that may influence individual responses.
- A description of the disease or condition being treated with the drug and how historically underrepresented populations are uniquely affected.
- A plan for recruiting and retaining clinical trial participants to achieve diversity goals.
Before the federal DEI rollback, submitting a Diversity Action Plan was required, but following it was not mandatory. If the drug company cannot achieve recruitment goals, the FDA’s guidance instructed them to submit a plan for gathering diversity data during the post-marketing period.
But is this enough? Dr. Yancy says no. “You can’t take a decades-old clinical trial design and all of a sudden say, ‘Okay, this is going to be a diverse trial’.”
Additionally, it’s common for drug companies to delay or neglect post-marketing studies intended to gather further safety and efficacy data after a drug’s approval.
Challenges and Opportunities in Recruiting Diverse Populations
When minority participation in clinical trials falls short, the FDA’s guidance suggested that drug companies may need to increase their enrollment to detect meaningful differences. For pharmaceutical companies, however, more participants often translate to higher costs.
In most cases, these efforts result in lost investments, given that only 12% of drugs that enter clinical trials are eventually approved for marketing.
These steep costs, coupled with the non-binding nature of the FDA’s guidance, can dissuade pharmaceutical companies from making the additional investment to ensure diversity.
Regardless of how seriously a drug company takes diversity recruiting, participation in clinical drug trials is always voluntary, and there are no guarantees that companies will be able to find the participants they’re looking for. In fact, it’s common for clinical trials to fail because researchers are unable to find and retain enough enrollees.
The challenges for recruiting a diverse population for clinical trials are numerous.“Clinical trials have an accessibility problem,” says Dr. Veintimilla, noting that most trials operate on a typical Monday-Friday, 9-to-5 work schedule.
It’s especially difficult for people with fewer resources to participate in clinical research, notes Bindu Balani, M.D., clinical primary investigator for clinical trials at Hackensack Meridian Health Research Institute. Trials may require three-hour-long appointments in the middle of the day, creating obstacles for those with childcare needs or less leniency around time off at work.
Medical mistrust is another significant barrier to recruiting diverse populations. It’s a deep-seated issue. Even today, many people don’t feel seen, heard or respected by the medical community. A majority of Black Americans report negative experiences in healthcare settings, according to a 2022 survey by the Pew Research Center.
A 2024 study identified several self-reported factors beyond race that can contribute to patients’ feelings of disrespect from medical providers, including appearance, income, education, mental health, and substance use history. Unsurprisingly, individuals who experienced these forms of discrimination reported higher levels of medical mistrust. Weight stigma, which is prevalent in healthcare settings, may also contribute to the higher rates of healthcare avoidance observed among women with obesity.
Dr. Balani emphasizes that researchers must reckon with past mistakes and focus on rebuilding trust, a vital step that may need to occur in tandem with drug companies’ efforts to enhance diversity in drug trials.
Creating More Inclusive Clinical Trials in the Future
Clinical trials must be designed with more flexibility, support, and telehealth built into the process, notes Dr. Veintimilla. Some of his suggestions include:
- Extending trial hours to include evenings and weekends.
- Better compensation for hourly wage participants who would lose some income by participating.
- Offering daycare or eldercare so caregivers can participate.
- Helping people pay for any out-of-pocket costs, such as travel to trial sites, by providing options like bus passes, taxis, or rideshares to help participants attend.
- Adding virtual visits when possible.
- More integration of clinical trials into local medical practices.
Dr. Balani wholeheartedly agrees that researchers need to be visible and meet people where they’re at. “It’s important to go to community fairs and participate in community health programs,” she notes. Likewise, Dr. Veintimilla says that researchers must be available to communities with questions or fears. But trust building is a challenge, he says, noting that people who work in clinical research “suffer from the same lack of diversity as the trials themselves.”
The lack of diversity extends upward into clinical research leadership, where decisions are made.
For example, one 2023 study found that Black, Hispanic, and female researchers are less likely to receive National Institutes of Health (NIH) grants compared to their white and male counterparts. These funding awards help sponsor scientific studies aimed at advancing knowledge in medicine, biology, and improving human health. Some of the reasons for this disparity include systemic biases in grant approval, access to mentorship, and research focus (some topics studied by underrepresented groups may not be deemed high priority by the NIH).
“A diverse research workforce who understands particular cultural backgrounds is important for building trust,” agrees Dr. Balani. She points out that researchers should be able to speak to patients in their language and at a level they fully understand.
Additionally, Dr. Yancy says there should be a voice at every level of oversight and leadership who understands health equity—from the sponsor (drug company) to the FDA, including clinical trial steering committees.
“If a pharmaceutical company intends to sell a product to varied populations, they have a duty to test it in those populations,” says Dr. Yancy. “This is not a political issue. It’s not even a social issue. It’s a people issue. Folks want to get good care. They want to know that the treatment that we prescribe will work for them.”
