This month the U.S. Food and Drug Administration (FDA) released its PDUFA V-mandated action plan to enhance the collection and availability of demographic subgroup data (age, sex, race and ethnicity) in applications for FDA-regulated medical products. The action plan was developed after an extensive FDA assessment of applications for recently-approved drugs, biologics and medical devices. The agency subsequently engaged in robust interaction with patient groups, provider organizations and industry to determine how to improve the completeness and quality of demographic subgroup data collection, reporting and analysis; how to identify barriers to subgroup enrollment in clinical trials and employ strategies to encourage greater participation; and how to make demographic subgroup data more available and transparent.
I attended a FDA meeting where a draft of this action plan was discussed for public comment. Many groups turned out to present their views on the underrepresentation of subgroups in clinical trials and the lack of accessible information available in product labels. While a lot of opinions were raised about what the FDA should require of those conducting clinical trials and what the FDA should do itself, there were few concrete suggestions from the community on how the agency could operationalize any of it. I am not surprised that some of these groups in attendance at the meeting were underwhelmed by the FDA’s final action plan. Their expectation was that the FDA should require inclusion of subgroups as a condition of drug, biologic and device approval. These individuals should not be surprised by FDA’s response. It is all that we can expect right now in order for there to continue to be drug, biologic and device development.
Clinical trial recruitment and retention of trial participants is difficult. Alzheimer’s disease is a well-documented example where you would expect to have a large number of people agreeing to participate in clinical trials given the increasing number of people with the disease and the lack of available treatments. Unfortunately, people affected by the disease are not lining up at the doors of trial sites saying, “Let me in.” It takes a tremendous amount of effort and time just to recruit the number of people necessary to show the effect from a new Alzheimer’s treatment. Many trials for this disease have suffered extensive delays in completing enrollment under current standards. Putting additional requirements on those running trials to include subgroups of the population based solely on age, sex, race and ethnicity as a condition for FDA approval will lead to further delays in development in an area where people with the disease have no time to spare.
I applaud those groups that have taken meaningful steps to chip away at the underlying problems behind the underrepresentation of subgroups. The Society for Women’s Health Research has worked with NIH to ensure that mouse studies of disease occur in mice of both sexes so that differences can be observed and documented. The National Minority Quality Forum launched a Clinical Trials Engagement Network to serve as a resource to improve the representation of African Americans, Asian Americans and Hispanics in clinical trials. These two separate actions are meaningful for different reasons. The first will lead to better knowledge of how sexes experience disease differently in order to demonstrate when subgroup information should be essential in clinical trials of new interventions. The second is aimed at accelerating the recruitment of a representative sample of diverse patients who are already anticipated to benefit from a proposed intervention.
Rather than wasting their voices talking to the press about how the FDA’s plan does not go far enough, groups that are disappointed with the state of drug and device development should be using their voices to call for representation of subgroups in basic research and encouraging older adults, women and all racial and ethnic minorities to volunteer for clinical trials. FDA has done its part on this issue. Now it is up to all of us to implement the changes that need to happen to increase subgroup representation in clinical trials.