The Milken Institute celebrates the publication of the second iteration of the Food and Drug Administration (FDA) draft guidance on Diversity Action Plans (DAP) to improve clinical trial diversity by enrolling underrepresented populations in the US.

FasterCures at the Milken Institute has been at the forefront of advancing health equity across the biomedical innovation ecosystem. In 2020, FasterCures initiated a body of work focused on developing strategies and policies to increase diversity and inclusion in all stages of clinical research and to change the culture of systems within the biomedical research community to value diversity and representation in the development and execution of clinical trials.

We also supported and applauded the inclusion of the DEPICT Act in the Food and Drug Omnibus Report Act of 2022 (FDORA), which aimed to remove barriers and improve diversity and inclusion in populations to involve participants in clinical trials mirroring the prevalence and incidence of diseases and conditions.

We believe the draft guidance created a pathway for diverse and inclusive clinical trials, particularly with the recommendations below within the guidance.

• The expanded categories for enrollment of underrepresented populations in the US include race, ethnicity, sex, and age, and disaggregated enrollment is required for categories.

• The FDA also encouraged sponsors to consider geographic locations, gender identity, sexual orientation, physical and mental disabilities, pregnancy status, lactation status, and co-morbidity as factors when developing the DAP.

• The FDA recommended that sponsors increase the proportional enrollment of a certain population (over-enrollment) to evaluate outcomes or other relevant factors in that group if they think certain populations might respond differently to the medical product.

• The guidance clarified that the prevalence or incidence among the US intended use population should be the foundation for determining the enrollment goals, except for products like vaccines targeting the entire population. For the latter, US Census data can be used. It encourages the industry to have ownership and leadership in designing clinical trials based on such data.

• For multi-regional clinical studies, the DAP requires the description of the participant enrollment goals for the entire study, not limited to US-enrolled participants. It also requires site selection to account for the need to enroll a population representative of the US intended use population.

We want to emphasize the key points below, which might need additional clarification and enforcement.

• It would be important to clarify what protocols the FDA would put in place if the enrollment goals were not met despite the best efforts from an industry sponsor. The first iteration of the draft guidance states, “In the event that recruitment goals are not met despite best efforts, sponsors should discuss with the FDA a plan to collect this data in the post-marketing setting.” This point is not repeated in the second draft guidance.

• The guidance states that sponsors should consider that "certain demographic groups may have a different response to medical products based on factors such as differential pharmacokinetics (PK), pharmacodynamics (PD),” etc. Although the FDORA requires sponsors to submit the DAP for phase 3 or other pivotal studies, it is essential to highlight that PK/PD studies are conducted in phases 1 or 2. These analyses determine an appropriate dose for a clinical trial. It will be necessary for the FDA and sponsor to ensure these factors are considered when setting enrollment goals.

“We look forward to working with the FDA to refine the guidance to maximize the full potential of the Diversity Action Plans,” said Esther Krofah, executive vice president of health at the Milken Institute. “It is imperative that clinical trials, and thus access to potential treatments and interventions, reflect prevalence and incidence of US intended population, including communities of color and other historically underrepresented populations.”