The Importance of Increasing Diversity in Clinical Trials

Before reaching the market, new drugs are tested in people who voluntarily participate in clinical trials. However, for a new medicine to work in as many people as possible, these drugs should be tested in a patient population that is as diverse as possible.

“I think about diversity through the lens of diversity, equity, inclusion, and accessibility,” explained Karriem Watson, DHSc, chief engagement officer of the All of Us Research Program at the National Institutes of Health (NIH).

“In broad terms, it emphasizes that people differ in many ways—such as race, ethnicity, gender, gender identity, sexual orientation, age, national origin, religion or spirituality, disability status, and socioeconomic background, including income, education, marital status, and even veteran status. Diversity also encompasses language, physical appearance, and diversity of thought. Where we live—rural versus urban areas—and our access to healthcare are also part of how we can understand diversity.”

Historically, however, clinical trials greatly lacked diversity of any definition and new medicines were tested primarily in white, middle-class male participants. This led to a growing problem, wherein drugs proven effective for white men often did not provide the same benefits to patients from diverse racial and ethnic backgrounds, to those assigned female at birth, or to other underrepresented groups.

“People from all backgrounds need medicine, and that means that for a new medicine to truly impact the people it is intended for, a diverse group of people need to be part of research studies,” explained Staci Hargraves, vice president of innovative health, engagement, and advocacy at Johnson & Johnson.

“Pharmacogenetic research has shown that there are significant differences among racial and ethnic groups in the metabolism, effectiveness, and side-effect profiles of many drugs. These differences can lead to varying drug outcomes and patient reactions.”

Watson added: “Diversity in clinical trials is not only about the ancestral and biological characteristics of people. A clinical trial design may not be diverse because it doesn’t include the lived experiences people can have. A drug may have to be taken in the morning—what about people who work shift jobs? Including the diversity of lived experiences in clinical trials can allow us to better understand how interventions can work both from a biological as well as from a social perspective.”

Efforts to increase diversity

In 1993, the United States Congress passed the NIH Revitalization Act¹, which aimed to increase the enrollment of “women and minorities” in clinical trials. Although the NIH Revitalization Act focused only on NIH-funded research, it was a first step toward increasing diversity in clinical trials and helped spread awareness to other trial organizers.

Since then, several regulatory documents and published guidelines have aimed to address this issue—and included several definitions of diversity—to help clinical trial sponsors increase diversity in clinical trials. For instance, most recently in June 2024, the FDA issued the draft guidance “Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies.” ²

Hargraves elaborated on this latest update: “Diversity action plans have changed so that they require enrollment goals for clinical studies to be broken down by race, ethnicity, sex, and age to reflect the diversity of the target patient population. Previous guidance recommended considering sex and age only, so this broader definition and requirement of inclusionary information is a notable shift.”

The data shows that efforts to enroll people who are assigned female at birth have been successful and participation in clinical trials has increased. However, despite continuous efforts, people of underrepresented backgrounds are still in the minority in most clinical trials.

The FDA’s most recent annual Drug Trials Snapshots summary report³ shows that the FDA approved 55 novel therapies in 2023, supported by pivotal studies involving around 44,000 participants worldwide. The report revealed that the percentage of female participants in clinical trials ranged from 41 to 67%, with a median of 48%. But for most of the approved drugs except three (Loqtorzi, Augtyro, Xacduo), white people comprised over 50% of the trial population, reflecting a continuous lack of ethnic and racial diversity in clinical studies.

So why are the majority of clinical trial participants white? Why is there still a lack of participation from underrepresented groups?

Addressing diversity challenges

“There are many factors that impact the perceptions certain communities have around clinical trials […],” Hargraves explained. “Lack of enrollment in clinical trials may be attributed to mistrust resulting from malpractice and maltreatment of certain communities throughout history. Other factors that impact diversity in clinical trials can also be the difficulty to reach certain underserved populations because of logistical factors like travel, accommodations, lack of access to childcare, or not being able to take time away from work.”

Clinical trial sponsors—pharmaceutical companies and contract research organizations—as well as various other organizations are working to increase diversity in clinical trials.

“We know that without tailoring medical care to all who need it, people will be left behind,” said Hargraves. “We see creating inclusive clinical trials as a critical first step. Reaching and recruiting participants from a variety of demographics is crucial to ensuring research is representative of the incredibly diverse communities served. We have several initiatives in place to increase clinical trial awareness and gain the trust of underrepresented and underserved communities.”

One example is the Johnson & Johnson Diversity, Equity and Inclusion in Clinical Trials team which collaborates with therapeutic area teams across the company to “embed diversity, equity, and inclusion into every stage of the clinical trial process.” The team also partners directly with patient advocacy organizations and works with communities to learn from patients of all backgrounds and increase diversity in clinical trials.

For Xoli Belgrave, senior director and head of clinical trial diversity and inclusion at Parexel, ensuring diversity in clinical trials begins by understanding the incidence and prevalence of an indication, by looking at the product’s pharmacokinetic–pharmacodynamic profile, and analyzing the history of other clinical trials for that indication.

“Unlike thirty years ago, we now recognize the importance of including diverse patient populations in clinical trials,” Belgrave said. “The work begins with making data-driven decisions and forming a container of the patient population. Based on what we learn from that, we can get a sense of where these patients are, geographically. Once we have the geography, our site selection should take us to a range of patients, ensuring that we include sites in urban, suburban, and rural settings, people of high and low socioeconomic status, patients with different abilities, homogenous racial communities, and multiracial communities.”

Organizations fighting for diversity

For clinical trial sponsors, increasing awareness and building trust within communities is essential to reach people from underrepresented groups. However, “We can’t do that on our own,” Belgrave emphasized.

“We need to partner with the communities themselves whether that is in the form of advocacy groups or community groups. Partnership is the way to go in this space because no organization can fix this on its own. We have to work with others and put aside our competitive differences for the sake of the patients. Let’s collaborate and try to make clinical trial access as easy as possible for patients.”

Examples of organizations that work to broaden awareness and clinical trial access for patients of underrepresented groups are the Lazarex Cancer Foundation, LUNGevity, and the NIH All of Us research program.

The Lazarex Cancer Foundation, for instance, helps people from underserved communities access cancer clinical trials by covering travel costs, assisting with trial navigation, and engaging with communities to reduce healthcare disparities and improve patient outcomes.

As part of the NIH, the All of Us Research Program aims to accelerate medical research and breakthroughs by collecting diverse health data so that everyone, especially those historically underrepresented in biomedical research, can benefit from precise, personalized medicine that considers the varied health needs of different communities.

“One of our core missions and values is to make research accessible to all,” Watson explained. “We also see the program participants as partners, and that means we have a model ensuring that our participants are involved in multiple levels of our governance, for example, helping to design our surveys or ensuring that our studies are responsive to the participants’ desires and needs.”

Some argue⁴ that the U.S. healthcare system favors people with higher socioeconomic status, making it more difficult for people with lower socioeconomic status to receive medical care and, by extension, learn about new medicines in clinical trials. The non-profit organization LUNGevity helps lung cancer patients access clinical trials but also supports patients in accessing organizations like Family Reach, which works to remove financial barriers so patients can receive their treatments.

Financial barriers remain key drivers of enrollment-related inequities in clinical trials. The financial status of an individual can influence whether they can afford to travel to a trial, cover the costs for food and childcare, or even take days off from work.

People with low socioeconomic status are disproportionately affected by this and can often not access the high-quality care and novel treatment options—especially if they have not responded to standard-of-care treatments—that clinical trials offer. In fact, research has shown⁵ that patients with yearly household incomes of less than $50,000 were 27% less likely to take part in cancer clinical trials.

Receiving financial reimbursement for trial-related expenses could increase diversity in clinical trials. Unfortunately, clinical trial sponsors still face legal hurdles in providing financial reimbursement. Recently, efforts have been made⁶ to simplify patient reimbursement for clinical trial participation. For example, the NIH “Allowable Costs Related to Participant Inclusion Activities” resource from November 2023 and two proposed bills, “The Clinical Trial Modernization Act” and “Harley Jacobson Clinical Trial Participation Income Exemption Act”.

Using technology to reach people

“There is more acknowledgment of certain barriers that exist within our healthcare system,” said Watson. “I want to encourage all clinical trial sponsors to consider two things: One is to eliminate the term ‘hard-to-reach’ populations and rather talk about ‘under-engaged’ populations. Two is to consider that these under-engaged communities can be in rural areas that may have limited access to technology. It is on us and our partners—everyone who is doing research—to think about access to technology and how patients will get to clinical trials in rural areas. Be intentional and address the barriers that prevent certain populations from participating in clinical trials.”

Many clinical trial sponsors are already using technology, including artificial intelligence (AI), to increase patient diversity in clinical trials. Johnson & Johnson, for example, uses AI in the planning and execution of its clinical trials and is using its AI-driven platform across approximately 50 clinical trials to increase diversity.

“Our AI platform enables us to combine real-world data to better identify where patients that meet our clinical trial criteria are geographically located,” explained Hargraves. “This informs our clinical site footprint and helps us identify new locations where there is a high probability of enrolling diverse patients. Through this approach in 2023 we saw that the average enrollment of Black patients in five Johnson & Johnson multiple myeloma trials was more than twice the historical industry standard.”

Belgrave added words of caution: “Technology is a friend and a foe. AI and technology have their place, but we mustn’t forget the people who are analog, we mustn’t forget about the human element. I believe a hybrid approach is the most helpful in terms of people participating in research. We can use technology to aid people in more rural locations—have tele-visits or use sensors to measure someone’s blood sugar, for example—but we need to shape the treatment around the patient without compromising them.”

Hope for the future

The most important thing to increase diversity in clinical trials is to stay intentional, Watson emphasized. “We need to ensure that there’s resources for community engagement because we know that it’s an effective approach to ensure diversity in clinical trials,” said Watson.

“We need resources for training and education of a clinical research workforce that truly reflects the populations that carry the greatest burden of disease, that has an understanding of the lived experience in underrepresented communities. Creating a diverse workforce will allow us to engage those populations historically underrepresented in clinical trials.”

“Ideally,” added Belgrave, “we won’t need people in the industry to talk about diversity in clinical trials in the future because it would be business as usual. We’d work ourselves out of a job. But in reality, I expect that politics and economics will influence the amount of investment we can make to ensure that clinical research involves diverse patient populations. We need to work to keep the voices of all patients in the room. We need to remember that, at the end of the day, the patients are why we do clinical research, and if we can keep the patients’ voices in the room, there will be a conscience that will keep us doing this work for as long as necessary.”

Read more:

History of Women’s Participation in Clinical Research, NIH Inclusion Outreach Toolkit: How to Engage, Recruit, and Retain Women in Clinical Research, National Institutes of Health.

Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies Guidance for Industry, Draft Guidance, U.S. Department of Health and Human Services, FDA.

Drug Trials Snapshots, Summary Report 2023, FDA Center for Drug Evaluation and Research.

Needed: a clearer explanation of why diversity in clinical trials is important, Arthur L. Caplan, STAT, June 2022.

Patient Income Level and Cancer Clinical Trial Participation, Joseph M. Unger, PhD; Julie R. Gralow, MD; Kathy S. Albain, MD; et al, JAMA Oncology, January 2016.

Could Financial Reimbursement Increase Clinical Trial Inclusivity?, Courtney P. Williams, DrPH; Mark E. Fleury, PhD; and S. M. Qasim Hussaini, ASCO Daily News, June 2024.

Larissa Warneck-Silvestrin is a freelance science journalist based in Berlin, Germany. She has a BSc in biology from Friedrich-Schiller University in Jena, Germany, and an MSc in science communication from the University of Kent in Canterbury, U.K. Larissa has written in English and German for several media outlets, including Labiotech, Deutsche Welle, and Inside Precision Medicine. She specializes in biotechnology, health, medicine, innovation, and biology.