By: Allen Pinn, Policy Coordinator

After years of advocacy work across the patient community and health care ecosystem, the Food and Drug Administration (FDA) issued updated draft guidance on clinical trial diversity earlier this summer. The draft guidance, which is open for public comment until September 20, provides a new outline for Diversity Action Plans (DAPs) to improve participation of historically underrepresented populations in clinical trials, and to improve data on patient use of medical devices and drugs approved by the FDA.

In the draft guidance, the FDA outlines how drug and medical device manufacturers should consider the responses to their products based on demographic groups, and how they should set recruitment goals based on race, ethnicity, sex, and age group. The FDA also recommends that manufacturers be transparent in their recruitment strategies. While DAPs will only be required for one of the four phases of clinical trials – Phase III of clinical trials, the FDA will encourage manufacturers to take a comprehensive approach to diversifying all four clinical trial phases. Below is an overview of the key aspects of the guidance.

Diversity Action Plans
DAPs emphasize the importance of enrolling and retaining participants of underrepresented populations in clinical trials with an overall goal of improving representativeness of the general population.

Enrollment Goals:

• Goals should be disaggregated by race, ethnicity, sex, and age group, reflecting the estimated prevalence or incidence of the disease in the US population.
• For rare diseases, achieving representative enrollment might not yield sufficient data to assess safety and effectiveness across all demographic groups. Sponsors should use available data sources, such as registries and epidemiological surveys, to estimate disease prevalence or incidence across different demographic groups where feasible.

Rationale for Enrollment Goals:

• Provide background information on the disease or condition.
• Include a detailed explanation if the goals deviate from the estimated disease prevalence or incidence in the intended population.
• Justify these goals with background information, detailed explanations, and any relevant data suggesting potential differences in drug or device response across populations.

Measures to Meet Enrollment Goals:

• Strategies to achieve these goals may include community engagement, cultural competency training for investigators, improved participant communication materials, reducing participant burden, and improving access to study sites.
• Consider factors like geographic location, gender identity, sexual orientation, socioeconomic status, disabilities, comorbidities, and pregnancy/lactation status when designing DAPs.

Regarding DAP submissions for biologics and drugs, the DAP must be submitted no later than the protocol submission for a Phase III or pivotal study. The FDA encourages submission at the End-of-Phase II meeting. As for devices, DAPs are required for Investigational Device Exemption (IDE) applications for significant risk devices. If an IDE is not required, a DAP must be included in premarket notifications, requests for classification, or premarket approval applications.

NHC Actions
The draft DAP guidance was required by legislation that NHC supported and was informed by earlier FDA draft guidance on which NHC provided input. Earlier this month, the NHC held an ad hoc meeting on the draft guidance with over 110 participants across multiple patient organizations, universities, research organizations, and medical companies who shared their initial reactions to and enthusiasm for measures that will assist in trial diversification. Input from that meeting will help inform the NHC’s response to the draft guidance, which we will publish by September 26.

Recent Congressional Action
Improving participation in clinical trials continues to gain support across the political spectrum on Capitol Hill. On May 16, 2024, Representatives Larry Bucshon (R-IN) and Raul Ruiz (D-CA) introduced H.R. 8412 the Clinical Trial Modernization Act (CTMA), the latest and most recent bipartisan effort to address the challenge. The CTMA addresses economic barriers that weaken clinical trial participation for people with serious or life-threatening conditions and would allow the Department of Health and Human Services (HHS) to issue grants to support outreach and recruitment for diseases that disproportionately affect historically underrepresented groups. Key features of the legislation include:

• Exempting free digital health technology that enables trial participation from the Anti-Kickback statute when doing so will facilitate clinical trial participation by underrepresented populations;
• Allowing patient cost-sharing by a drug or device manufacturer in a clinical trial when specific criteria are met, and;
• Excluding remuneration for participation in clinical trials from taxable income.

NHC Actions
The NHC has signed on to support the CTMA, as well as several earlier clinical trial diversity bills, and will continue to work with members of Congress to advance legislation that supports diversity in clinical trials.

If you have any questions about the NHC’s upcoming comments on the draft guidance, please contact Eric Gascho, Senior Vice President, Policy and Government Affairs at egascho@nhcouncil.org.