The Power of Inclusion: Navigating the FDA’s Diversity Action Plan

In December 2022, Congress passed the Food and Drug Omnibus Reform Act (FDORA), which requires, among other things, that drug and device sponsors submit diversity action plans for clinical trials that commence enrollment 180 days after publication of the final guidance. FDORA codifies a long-standing push by the US Food and Drug Administration (FDA) to ensure that the populations studied in clinical trials are representative of patients who will be treated with the drug or device in clinical practice and reflect US demographics. To that end, the FDA just published, in June 2024, a Draft Guidance for Industry titled Diversity Action Plans to Improve Enrollment of Participants From Underrepresented Populations in Clinical Studies,¹ which is open for public comment for 90 days. So, you should be asking yourself, do you have a diversity action plan for your planned clinical trials?

When the FDA talks diversity, the Agency is thinking beyond race and ethnicity. The FDA definition of diversity includes age, sex, race/ethnicity, gender identity, pregnancy status, lactation status, comorbidities, disability, and socioeconomic status. All these need to be considered, as appropriate, when developing a diversity action plan. The goals are to ensure that clinical trials better reflect the diversity of populations expected to use a product and identify potential effects on safety or efficacy associated with, or that may occur more frequently within, certain subpopulations.

The FDA expects diversity action plans to

1. Identify operational measures to facilitate enrollment of representative numbers of participants from clinically relevant, underrepresented populations in clinical trials
2. Ensure adequate participation and analysis of data collected from those subpopulations

Why is this important?

When clinical trials are not representative of patients who are most likely to use a product, knowledge gaps are created in our understanding of the safety and efficacy of that product in distinct subpopulations of patients.² Diverse trial populations contribute to a more accurate assessment of a medical product and ultimately improve the quality of healthcare decision making.² According to the FDA’s guidance,¹ consistent implementation of actions to improve representativeness in clinical studies can achieve a number of goals, including

• Supporting more equitable and timely access to medical discoveries and innovations
• Improving the generalizability of results across the intended patient populations
• Improving our understanding of the disease and/or medical product under study
• Informing the safe and effective use of the medical product for all patients

The first step is to identify underrepresented populations in clinical trials. For example, Black/African Americans represented ~13.6% of the US population in 2021; however, their average representation in clinical trials was only ~7% of study populations (2015-2019 estimate).³ Other underrepresented populations include older individuals (eg, >65 years of age); individuals with significant comorbidities such as heart, liver, or kidney disease; pregnant women; and individuals with lower socioeconomic status.

Demographics of trial participation in the US (2015-2019)⁴

Underrepresentation in clinical trials of certain segments of the population can occur for a variety of reasons, including lack of knowledge or understanding of medical research and historical distrust of medical research. In other cases, certain groups (eg, older individuals and those with significant comorbidities) may be excluded from clinical trial participation by recruitment criteria.

What should a diversity action plan contain?

There are 5 key elements that should be include in a diversity action plan, as follows.

1. Disease Overview: An assessment of data that may indicate the potential for a medical product to have differential safety and/or efficacy profile within a clinically relevant, underrepresented group demographic.
2. Trial Design: The intended assessment of the identified underrepresented populations in addition to other factors with known potential to affect the safety and/or efficacy of the product. These planned assessments should also be detailed in the protocol and the statistical analysis plan. In addition, the plan should describe the intended study population, including eligibility criteria, comorbidities, geographic locations, etc, and how these will address inclusion of underrepresented populations.
3. Enrollment Goals: Enrollment goals for underrepresented participants, disaggregated by race, ethnicity, sex, and age group, should be defined as early as possible, based in part on the prespecified protocol objectives of the study. This should include a description of potential barriers to enrollment, such as patient population size and geographic location. The plan must also include the sponsor’s rationale for the enrollment goals with sufficient information and analysis to explain how the sponsor determined its enrollment goals.
4. Operational Measures: Detailed measures and metrics to enroll and retain potential participants with underrepresented demographics, including site location and access, sustained community engagement, and decreasing trial-related burden. Enrollment strategies may include demographic-specific outreach, study-site selection, inclusion and exclusion criteria, and diversity training for trial personnel.
5. Status Updates: Outline the plan to collect data and explore the potential for differences in safety and/or efficacy in underrepresented group demographics throughout the entire development life cycle of the product and not just during the pivotal trial(s). This should include status of enrollment goals and action(s) to be implemented if those goals are not met.

When should a diversity action plan be discussed with the FDA?

The diversity action plan is typically discussed with the FDA at or before the end of phase 2 meeting and is an important part of seeking feedback from FDA on the pivotal trial design. Feedback on the plan may be requested by including specific questions in a formal milestone meeting request or meeting package and should be included in the marketing application, along with a description of the successes and challenges in implementing the plan. According to the new draft guidance, sponsors must submit the required diversity action plan as soon as practicable but no later than the date on which the sponsor submits the protocol to FDA for the phase 3 or other pivotal study.

Where can you go for help?

Healthcare Communications Group (HCG) has a Diversity, Equity, Inclusion, and Belonging Council and is uniquely positioned to help our clients address disparities and inequities in clinical trials. We can help raise awareness, train and educate key stakeholders, and report diversity information from clinical trials. Given our expertise in this area, we can support our clients in several ways.

• Support development of multilingual, patient-friendly recruitment materials that are more accessible and inclusive to support patient education across populations
• Identify gaps, unmet needs, and target populations in clinical development programs
• Support protocol and diversity action plan development and review
• Develop training and education materials for investigators and other healthcare providers involved in clinical trial enrollment and patient care
• Contextualize and report diversity information associated with clinical trial results

If you are involved in clinical research, it’s important to recognize that a diversity action plan is a mandatory strategic blueprint that is required from sponsors for ensuring diversity among clinical trial participants. HCG remains committed to addressing diversity in clinical trials, and we can help our clients in this area.

Jeff Riegel, PhD
SVP, Scientific Communications

Jeff combines his scientific expertise in molecular biology and immunology with more than 28 years of global healthcare agency experience guiding medical and regulatory communication strategies for biopharma companies. Jeff helps clients prepare for FDA Advisory Committee meetings and other health authority interactions. Connect with Jeff on LinkedIn.

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References:

1. U.S. Department of Health & Human Services. Diversity Action Plans to Improve Enrollment of Participants from Underrepresented Populations in Clinical Studies Guidance for Industry. June 2024. Accessed July 3, 2024. https://www.fda.gov/media/179593/download.
2. National Institutes of Health. Accessed June 15, 2023. https://www.nimhd.nih.gov/resources/understanding-health-disparities/diversity-and-inclusion-in-clinical-trials.html.
3. United States Census Bureau. Accessed June 15, 2023. https://www.census.gov/quickfacts/fact/table/US/PST045221.
4. US Food and Drug Administration. 2015-2019 Drug Trials Snapshots Summary Report.