The FDA's recent draft guidance on diversity action plans (DAPs) aims to enhance the inclusion of underrepresented populations in clinical studies. Mandated by the 2022 Food and Drug Omnibus Reform Act (FDORA), the guidance outlines requirements for sponsors to develop and submit DAPs for Phase 3 and pivotal trials. This initiative focuses on improving the representation of diverse groups, including age, sex, race, and ethnicity, in clinical trials.
Establishing Enrollment Goals: A Key Challenge
One of the most debated aspects of the draft guidance is the establishment of enrollment goals. Sponsors are expected to set goals based on the estimated prevalence of the relevant disease in the U.S. intended use population. However, determining accurate prevalence estimates can be difficult due to the limitations and potential biases of available data sources, such as registries, literature, and electronic health records.
David Peloquin, a partner at Ropes & Gray, noted, "In many cases, it will be difficult to arrive at a prevalence estimate for a condition in the U.S... sponsors will need to consider the limitations and potential biases of each data source, and potentially rely on multiple data sources to come up with a prevalence estimate for their DAP."
For multi-regional clinical trials, the guidance states that enrollment goals should align with the U.S. intended use population, which presents logistical challenges. The FDA acknowledges the difficulties in setting enrollment goals for international sites due to the lack of uniformity in population descriptors across the globe.
Measures to Meet Enrollment Goals
The draft guidance suggests various measures for sponsors to meet diversity enrollment goals, including decentralized study designs. Decentralization can potentially improve access for underrepresented groups, including those in rural areas far from academic medical centers.
Peloquin added, "This is not the first time FDA has said decentralization has the potential to assist in reaching underrepresented groups in clinical trials... it adds to the momentum we’ve seen among industry and other stakeholders as well as at FDA itself to foster the use of decentralized trials in cases where a decentralized design may make sense."
Consequences of Missing Enrollment Goals
A significant concern among sponsors is the outcome of failing to meet enrollment goals. While the guidance does not specify enforcement mechanisms, the FDA has tools to address non-compliance. Sarah Blankstein, counsel at Ropes & Gray, suggests that the FDA might use post-marketing requirements (PMRs) and post-marketing commitments (PMCs) to gather additional data on underrepresented subgroups post-approval.
Blankstein stated, "Realistically, I’d expect it to depend on a variety of factors like how far off the sponsor was, the impact of the missed goal on the sufficiency of the data in a given subgroup, the reasons the sponsor missed their goal, as well as the interactions that they’ve had with FDA along the way."
Impact of the Presidential Election
The upcoming presidential election introduces uncertainty regarding the future of the DAP guidance. A new administration could potentially lead to changes in the final guidance, particularly concerning diversity, equity, and inclusion (DEI) efforts.
Peloquin commented, "Maybe DAPs don’t get wrapped up in any efforts to minimize focus on DEI generally, but it’s certainly possible, and in that case, maybe we see a much less rigorous version of the DAP guidance when it’s finalized."
Waivers and Data Privacy
The statute allows the FDA to issue waivers from DAP requirements based on the prevalence of the disease in the patient population. However, the FDA has indicated that waivers will be infrequent, even for rare diseases. Industry groups have pushed back on this approach, arguing for more flexibility.
Data privacy is another critical consideration. Sponsors must comply with U.S. state and international privacy laws, such as GDPR, when collecting information to meet DAP requirements. These laws often treat race and ethnicity as sensitive information, requiring additional protections.
