We have written before about the persistent problem of insufficient diversity in clinical trials. Adequate representation of patient diversity is important as older adults, children, pregnant women, and racial and ethnic minorities are often affected differently by health conditions and may respond to treatment in a variety of ways. To add to that, individuals with co-morbidities or those who are otherwise taking multiple medications further contribute to the diversity in patient populations. Despite efforts over the last decade to increase representation of these diversities in clinical trials, many groups – especially racial and ethnic minorities – still remain significantly under-represented compared to the incidence of the relating health problem in those particular populations. For example, only 8 of the 101 new drugs approved in the United States in 2019 and 2020 included an enrollment of black and Hispanic participants proportional to the indicated condition’s prevalence in those populations. Such limited trial diversity has led to delayed discoveries of population-related adverse event risks, as well as potentially overlooked treatment benefits for specific patient populations.
In April 2022, the U.S. Food and Drug Administration issued draft guidance to industry for increasing diversity in U.S. clinical trials, especially among under-represented racial and ethnic groups. The guidance called for trial sponsors to submit a “Race and Ethnic Diversity Plan” to the agency in the early planning process when clinical studies are intended to support marketing approval for drugs or certain types of medical devices. Such plans would be required to include defined enrollment goals aimed at understanding how treatment outcomes might vary across racial and ethnic groups. They would also require the sponsor to describe specific measures to be undertaken to ensure enrollment and retaining of trial participants. Sponsors would furthermore need to discuss the expected challenges in implementing diversity plan requirements and how success in meeting plan objectives would be defined. Consequently, the guidance also calls for sponsors to discuss potential changes to the diversity plan if enrollment goals fall below expectations. On their side, the FDA’s Office of Minority Health and Health Equities would provide sponsors with overall support for meeting diversity objectives through an ongoing public health education and outreach campaign to the targeted populations.
While experts considered the FDA’s draft guidance a step in the right direction, it lacked any legal force. However, in December 2022 the U.S. Congress passed Public Law 117-328, included in the Food and Drug Omnibus Report Act. The law now requires clinical trial sponsors to submit a diversity action plan and specific enrollment goals early in pivotal trial planning, including specific strategies for reaching a broad study population.
Efforts to significantly tackle the diversity problem can substantially increase the time and cost of clinical trials. Sponsors will need to address a number of obstacles to enrolling and retaining a diverse population, including language barriers, accessibility to clinical trial sites, and the frequency of required site visits. A February 2022 report issued by the National Academy of Sciences and opinions from other industry advisers suggest the FDA could help balance these challenges and drive compliance by providing incentives to trial sponsors through the expansion of existing regulatory programs – such as tax credits, fast track eligibility, reduced fees, or extended market exclusivities – to those who meet diversity goals. They also suggest that the FDA might aid patient recruitment and retention within minority populations by giving trial sponsors more freedom to reimburse study participants, and to cover their expenses for transportation costs, dependent care, and lost wages. The FDA has a year to issue its final guidance, and there could be waivers and exceptions issued for some types of trials, such as bioequivalence studies.