The increasing trend toward conducting global trials has watered down representation of some U.S. ethnic and racial minorities in drug development, according to one FDA official.

While there are some benefits to global trials, said Jamie Brewer, clinical team lead with the FDA’s Office of Oncologic Diseases, such as capitalizing on different geographic regions, the agency’s view of such trials is that they dilute racial and ethnic minority representation compared to the U.S. population.

The FDA’s definition of diversity goes beyond racial and ethnic demarcations, Brewer stressed, encompassing a range of clinical, demographic, geographic and social dimensions, including differences in gender and sexual orientation.

“While we want to continue fast drug development and getting drugs on the market quickly,” she told attendees at this year’s SCOPE Summit, “we also want to make sure … that these drugs are evaluated in clinical trial populations that are representative of the population that it is intended [for] when the drug product comes to market.”

“In many disease settings, but specifically in oncology, we’re seeing that more and more trials are being conducted across an international landscape, so there’s more global drug development,” Brewer noted. While this approach may have been taken for a multitude of reasons that help propel the development of drugs in general, “we notice that it kind of changes the composition of our clinical trial populations.”

She noted that most multinational clinical trials occur in Europe and Canada and other countries with predominantly White populations, while Latin America and Africa get left behind as trial locations. Diversity in trials not only increases generalizability of study results by evaluating variable effects in diverse populations, stressed Brewer, but is also a critical factor in ensuring more adequate access to trials, often the recommended treatment step for patients.

While the FDA wants to encourage global drug development, sponsors must be more intentional in enrolling and submitting trials that have populations more representative of the U.S., she said. The increasing trend toward conducting trials abroad has led to fewer U.S. citizens being part of clinical trials of drugs approved by the FDA and intended for use in the U.S.

In addition, Brewer took aim at excessively restrictive eligibility criteria that often fail to define a trial population that represents the disease population in the real world. To combat this, Brewer said the FDA has issued multiple guidances aimed at broadening study eligibility criteria and increasing diversity, including an April 2022 draft guidance encouraging sponsors to develop a diversity plan for each trial (CenterWatch Weekly, April 18, 2022).

The guidance is intended to establish an opportunity for the FDA to engage with industry and other stakeholders on strategies for enrolling diverse populations. “This should really begin early in the drug development or clinical development program or pipeline,” Brewer said, “in those early dose-finding and pharmacokinetic studies, in the activity-estimating studies, all the way through the clinical development pipeline to the postmarketing setting.”

But, she explained, “the guidance is intentionally not prescriptive on the specific measures or approaches that must be included in whatever strategy is used to achieve diversity on a clinical trial.” Instead, she said, the guidance is meant to serve as framework “to think about what strategy should be present, how likely is this strategy to work, is this strategy appropriate for this particular patient population based on the epidemiology of the disease?”

The FDA wants to ensure that any diversity strategy is fully integrated into the clinical development program at both the beginning and end of the program, Brewer said, with reassessment of the diversity plan following talks with the agency.