General

Clinical Trials Not Sufficiently Diverse – and Diversity Data Often Not Reported

May 9, 2022 – New analyses of clinical trials conducted in the United States and in Europe on potential new drugs found that not only were study populations not as diverse as the general population, but that frequently no race or ethnicity data was included in the trial reports, and sometimes not even gender data.

These findings come at a time of  general consensus that increasing the diversity of subjects in clinical trials is both a desired and necessary way of ensuring that drugs are safe and effective for minority patients, and just as Commissioner Robert Califf, M.D., announced a new draft guidance as part of the Food and Drug Administration’s (FDA’s) effort to encourage greater trial diversity.

One study, published April 10 in The Lancet Regional Health-Americas, found that only 43 percent of all U.S. clinical trials registered on ClinicalTrials.gov from March 2000 to March 2020 reported any race or ethnicity data on patients. This analysis, by Brandon Turner and colleagues at Massachusetts General Hospital and Stanford University, included 20,692 trials representing about 4.6 million enrollees. Among the trials that did report diversity data, minorities were under-represented in comparison to their proportions in the general population, although there was small improvement over time.

“U.S. trials under-enroll racial/ethnic minorities and frequently do not report their minority enrollment at all,” the authors wrote. “This disparity contributes to biased medical evidence and excludes minorities from the benefits of clinical trial participation.”

Meanwhile, a May 4 STAT article cited a recent study by the Tufts Center for the Study of Drug Development, which found that between 2007 and 2019, only two-thirds of “pivotal clinical trials” (usually phase 3 trials) in Europe reported any data on race of participants, and only one-third reported data on ethnicity. There was lax reporting even of enrollees’ gender; this was reported in only 61 percent of trials run from 2007 to 2010, although the percentage rose to 91 percent among trials from 2017 to 2019. The Tufts analysis included 943 trials conducted for more than 440 drugs seeking European Commission approval.

“Dr. Janet Woodcock, now the Principal Deputy Commissioner, speaks of the need to enroll a population that ‘looks like this country,’” noted Jon Bigelow, executive director of the Coalition for Healthcare Communication “These reports reflect yet another difficulty in assessing whether clinical trials reflect the efficacy and safety of new medicines across the full range of patients to whom they may be given.”

In an April 13 announcement of a new FDA draft guidance for industry on enrolling more participants from underrepresented racial and ethnic populations, Califf said that “going forward, achieving greater diversity will be a key focus throughout the FDA to facilitate the development of better treatments and better ways to fight diseases that often disproportionally impact diverse communities.”

Califf noted that the new guidance, which expands on the agency’s previous guidance on this issue and is aligned with the Biden administration’s Cancer Moonshot goal of addressing inequities in cancer care, will help to make sure that “every community in America has access to cutting-edge cancer diagnostics, therapeutics and clinical trials.”

Specifically, the draft guidance – “Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Subgroups in Clinical Trials” – recommends that sponsors of medical products develop and submit a Race and Ethnicity Diversity Plan to the agency early in clinical development, based on a framework outlined in the guidance. Such plans should define enrollment goals for underrepresented racial and ethnic participants as early as practicable in clinical development for a given indication, and include data collection goals.

It is worth noting that these plans are not required, but the FDA states in the draft guidance that “the collection of sufficient pharmacokinetic (PK), pharmacodynamic (PD), and pharmacogenomic data from a diverse population is strongly encouraged to inform analyses of drug exposure and response.”

Bigelow noted that the situation is improving, but still not great.

“A priority for the FDA is to engage more patients in clinical trials from groups that have previously been underrepresented, including people with various racial and ethnic backgrounds, seniors, rural residents, pregnant and lactating women, and rural residents,” Bigelow said. “The new draft guidance reflects the FDA’s determination to see progress.”