FDA’s New Post-Market Diversity Expectations
(Thursday, August 17, 2023)
Despite extensive advocacy from the FDA, most pre-approval clinical trials lack diversity owing primarily to the unwillingness of certain segments of the population to participate in clinical trials. However, once a drug is approved by the FDA, its use is more diverse and representative of the demographic distribution of the general population. To take advantage of that, the FDA is proposing that post-market trials be used to collect drug usage data from diverse populations. Under a new guidance released recently, FDA could ask the manufacturers of newly approved drugs to collect clinical data from diverse populations via a post-market requirement (PMR) or a post-market commitment (PMC).
Clinical trials often lack diversity, leaving gaps in our understanding of how drugs work across various groups. The FDA recognizes that women, older adults, racial and ethnic minorities, and non-heterosexual subjects are often underrepresented. To combat this issue, the FDA encourages early collection of data from diverse patient groups during drug development. But FDA’s requirement of a diversity plan for clinical trials and robust efforts by the industry in recruiting underrepresented populations in their trials have been unsuccessful so far in assuring such populations in pre-market clinical trials.
Acknowledging the challenges of gathering data from underrepresented populations before approval, the FDA's draft guidance focuses on post-marketing strategies for a more comprehensive view of product performance. When existing data in the market approval application on adverse events or risks are insufficient, the FDA issues a PMR as a condition for approval. For instance, if a particular adverse event affects a specific group but was not well-studied, a PMR can trigger further evaluation in a diverse population in post-marker clinical trials. Alternatively, the FDA and sponsors can reach an agreement to conduct additional studies post-approval under a PMC where the sponsors collect more safety and efficacy data through trials or real-world sources.
There are four ways to collect such post-market clinical experience data from diverse populations. First, single-arm trials with statistically powered sample size can be conducted where the drug is administered to specific subpopulations to evaluate its safety and efficacy. Second sponsors can collect and review real world data from electronic health records and registries to get insights into drug performance in diverse populations. Third, sponsors can pool data from various trials (pre- and post-market) for broader assessment of drug performance across diverse subpopulations. All three of these trials can be conducted relatively easily because once a drug is approved by the FDA, underrepresented populations will likely be more comfortable getting these treatments. The fourth way is the classical randomized clinical trials where the sponsor can aim to include higher proportion of underrepresented groups, although such trials would be harder as post-approval giving a patient a placebo or an inferior control may raise ethical concerns.
FDA is open to meet with the sponsor to discuss the post-market trial designs. FDA also is supportive of the sponsors collecting post-market data in underrepresented populations in international clinical trials with assurance of the application of data from other countries to the US population and medical practices.
With this new guidance, the FDA has added one more way to address the acute shortage of data from certain populations segments not represented proportional to their share of the population. This approach seems more feasible for the sponsors, and acceptable to the targeted populations.
Dr. Mukesh Kumar
Founder & CEO, FDAMap
Linkedin: Mukesh Kumar, PhD, RAC