Diversity Action Plan Guidance Part I: Implications for Sponsors

When we consider unmet need in drug development, we typically think of specific indications or disease states for which safe and effective therapies do not exist.  If we zoom out to look at it from a societal level through a regulatory lens, we see an impetus to address broader unmet needs in the history of Food and Drug Law.  Examples include the need for a means to ensure properly branded and unadulterated drugs, leading to the passage of the 1906 Food and Drug Act, and the need to prevent dangerous or ineffective drugs from entering the market, resulting in the passage of the Kefauver-Harris Drug Amendments in 1962. 

As the science behind regulatory approvals advances to incorporate smaller patient populations, novel study designs, surrogate endpoints, and real-world evidence, an important unmet need has become increasingly apparent:  the need for drug approvals supported by generalizable data obtained through recruiting more diverse patient populations.  This is the focus of the FDA’s recently released draft guidance “Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies”, which is a highly anticipated update to the Agency’s 2022 draft guidance “Diversity Plans to Improve Enrollment of Participants From Underrepresented Racial and Ethnic Populations in Clinical Trials.”  While the two guidances are similar in many respects, sponsors should understand that the 2024 guidance is also supported by laws which succeeded the 2022 guidance.  This and other important differences are summarized below: 

Legal Foundation:

While the 2022 guidance was non-binding, the updated guidance will have a binding effect upon finalization.  Section 3601 of the Food and Drug Omnibus Reform Act of 2022 (FDORA) describes the specific legal requirements for Diversity Action Plans.  Starting 180 days after publication of the final diversity guidance, sponsors planning pivotal clinical studies for the approval, licensing, or clearance of most drugs and devices must submit a Diversity Action Plan when they submit key trial documents to the FDA.  

Expanded Definition of Diversity:

The scope of the new guidance has expanded beyond the racial/ethnic definition of diversity described in the earlier guidance to include additional factors such as gender, age, and socioeconomic status.  This expanded scope is in line with the goals of FDORA and is anticipated to increase diversity in pivotal trials by: 

• tailoring recruitment strategies to address barriers unique to specific underrepresented groups,
• reinforcing more inclusive and representative data collection through a wider range of demographic factors, and
• strengthening collaboration with community organizations, patient advocacy groups and stakeholders to engage diverse groups.

Waiver Process:

The updated guidance also details the criteria for sponsors seeking a waiver of the Diversity Action Plan Requirements under section 505(z)(4) and section 520(g)(9)(C) of the FD&C Act (as amended by section 3601 of FDORA). Based on the following criteria,  FDA may waive (with a full or partial waiver) the requirement to submit a Diversity Action Plan either on the Agency’s initiative or at a sponsor’s request:

• the prevalence or incidence in the U.S. of the disease or condition that the patient population that may use the drug or device 
• conducting a clinical investigation in accordance with a Diversity Action Plan may be impracticable
• it’s necessary to protect public health during a public health emergency

Sponsors are advised to submit the waiver request early in the planning stages of the clinical study or clinical development program, but no later than 60 days before the Diversity Action Plan is required.

Diversity Action Plan Content and Monitoring: 

The updated guidance is also more specific in describing the content of Diversity Action Plans, including specific recommendations for enrollment goals and associated rationales as well as guidance on measures to meet goals for both enrollment and retention.  The section is notable for contextualizing diversity planning as an ongoing and iterative process during which the effectiveness of plans can be assessed and adjusted throughout the clinical trial.  Stay tuned for part II on this topic, which gives expert insights on how such monitoring plans might be conducted.

The Future of Diversity Action Plans

Sponsors should note that the comment period for the current draft guidance closes on Sept 26, 2024 and that FDORA requires the FDA to finalize the current draft guidance within 9 months of the comment period closing.  The requirements for Diversity Action Plans will go into effect 180 days after finalization of the guidance.  Based on these targets, sponsors can expect these requirements to legally go into effect around Q4 of 2025.  Given the complexity and need for advance planning associated with large pivotal trials, as well longer-term considerations for pooling data across studies, sponsors should begin considering how these guidelines might affect their clinical development plans now.  Timely engagement with the Agency will be critical in ensuring strong and generalizable data in future NDAs and BLAs.  For more information on how to structure these or other critical regulatory engagements, please contact us at (email) or using the question box below.

References https://www.fda.gov/news-events/press-announcements/fda-guidance-provides-new-details-diversity-action-plans-required-certain-clinical-studies

This article was written by
Nancy Hsu, Regulatory Affairs Associate,
Ben Kaspar, Regulatory Affairs and Strategic Consulting Senior Director at MMS Holdings