WASHINGTON — A new congressionally mandated report from the National Academies of Sciences, Engineering, and Medicine calls for urgent actions by federal agencies, Congress, journals, and others to improve the representation of racial and ethnic minority groups and other underrepresented populations in clinical trials and research.

Currently, lack of representation in research is compounding disparities in health outcomes, with serious consequences for underrepresented groups and the nation as a whole, said the committee that wrote the report.

“While U.S. investments in clinical research have contributed significantly to treating and preventing disease and extending human life, large swaths of the population are less able to benefit from these discoveries because they are not adequately represented in clinical research studies,” said committee chair Kirsten Bibbins-Domingo, chair of the department of epidemiology and biostatistics and professor of medicine at the University of California, San Francisco. “As the U.S. becomes more diverse every day, failing to reach these growing communities will only prove more harmful and costly over time.”

Improving representation in research would help to reduce disparities in health outcomes and the harm they cause, along with their economic toll, said the committee.

The High Health and Economic Costs of Underrepresentation
An equitable clinical research enterprise would include trials and studies that match the demographics of the disease burden under study, but the nation remains far from achieving this goal, the report says.

Although there has been progress on some fronts — particularly with representation of White women in clinical trials and research — it has largely stalled on participation of racial and ethnic minority population groups. In addition, older adults, pregnant and lactating individuals, LGBTQIA+ populations, and people with disabilities remain underrepresented and even excluded from clinical trials and clinical research.

This underrepresentation has serious consequences, the report says, including:

• Lack of representation may lead to lack of access to effective medical interventions. Approval and indications for new therapeutics are often restricted to the demographics of the populations included in the clinical studies. Lack of representation may therefore impede access to a specific therapeutic agent for some groups of patients.

• Lack of representation compounds health disparities in the populations currently underrepresented and excluded in clinical trials and clinical research. While achieving health equity and reducing health disparities requires far more than just equitable representation in clinical research, failure to achieve this leaves these disparities unaddressed and reinforces inequities.

• Lack of representation costs hundreds of billions of dollars. An economic analysis carried out by the committee demonstrates high financial and social costs — measured by life expectancy, disability-free life, and years in the labor force — projected to be in the hundreds of billions of dollars range over the next three decades. If better representation in clinical trials reduces health disparities by even a modest amount, the analysis found that achieving diverse representation in research would be worth billions of dollars in savings to the United States.

Underrepresented Populations Willing to Participate, If Asked
Distrust and mistrust are commonly assumed to be the reason underlying lack of participation in clinical trials, the report notes. While there is no doubt that the legacy of abuses in medical research is an important factor driving the lack of engagement of underrepresented populations with research, several studies have found that distrust and mistrust are not necessarily associated with a lack of willingness to participate. Evidence shows that Asian, Black, and Latinx Americans, and American Indian/Alaska Native individuals are no less likely, and in some cases are more likely, to participate in research if asked, the report says.

Actions Needed to Drive Systemic Change
Improving representation is the responsibility of everyone involved in the clinical research enterprise, and a range of steps are needed to change the nation’s approach to clinical research to more equitably recruit and retain a diverse group of participants, the report says. Its recommendations focus on system-level actions to drive change on a broad scale.

Among the report’s recommendations:

• The Food and Drug Administration should require study sponsors to submit a detailed recruitment plan no later than at the time of submission of the Investigational New Drug and Investigational Device Exemption application that explains how they will ensure that the trial population appropriately reflects the demographics of the disease or condition under study.

• The Office of Human Research Protections (OHRP) and the FDA should direct local institutional review boards (IRBs) to assess and report the representativeness of clinical trials as one measure of sound research design that it requires for the protection of human subjects.

• To determine how to take action on the most effective accountability and incentive structures, Congress should direct FDA to enforce existing accountability measures and establish a taskforce to study new incentives for new drug and device trials that achieve representative enrollment. Some ideas include tax incentives, fast-track criteria and exemption from some FDA drug application fees, extended market exclusivity to sponsors who meet predefined criteria of representativeness, and refusing to file an application that does not appropriately represent the target population under study.

• In grant proposal review, the NIH should formally incorporate considerations of participant representativeness in the score-driving criteria that assess the scientific integrity and overall impact of a grant proposal.

• Journal editors, publishers, and the International Committee on Medical Journal Editors should require information on the representativeness of trials and studies for submissions to their journals, particularly relative to the affected population; should consider this information in accepting submissions; and should publish this information for accepted manuscripts.

“While we all bear the cost of excluding women, racial and ethnic minority groups, LGBTQIA+ populations, people with disabilities, older adults, and pregnant and lactating individuals from clinical trials, the populations left out of research bear the greatest cost, as they may lose out on benefiting from the United States’ substantial investment in scientific advancement and may be deprived of access to novel treatments,” said Victor J. Dzau, president of the National Academy of Medicine. “All stakeholders in the research enterprise must take committed and accountable actions in order for our country to have a diverse, inclusive clinical research portfolio.”

The study — undertaken by the Committee on Improving the Representation of Women and Underrepresented Minorities in Clinical Trials and Research — was sponsored by the National Institutes of Health. The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine. They operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln.

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