Diversity in Clinical Trials: FDA Draft Guidance on Diversity Action Plan Requirements

This blog was authored by Ashni Parekh, Global Compliance and Strategy Analyst at Medidata.

The topic of diversity in clinical trials has received much attention from the FDA over the past few decades, but this wasn’t always the case. In 1977, the FDA recommended that women of childbearing potential be excluded from clinical trials, due to their fluctuating hormones, making them a more complex group to treat. Until the NIH Revitalization Act of 1993, which mandated the inclusion of women and minorities, clinical trials mostly comprised white men. Since the early 90’s the FDA has taken steps to improve diversity and inclusion in clinical trials by introducing numerous guidelines and mandates. 

The highly anticipated draft guideline, Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials as part of the Federal Drug and Omnibus Reform Act (FDORA)^[1], was recently released on June 26th, 2024. This is an updated version of the draft guidance released in April 2022, prior to the enactment of FDORA.

This new guidance substantiates the content to be included in the Diversity Action Plan (DAP), which will be required upon late-stage trial protocol submission, as outlined in FDORA. Unlike most other FDA draft recommendations, which are not legally binding, this draft guidance will create legally binding guidelines that are expected of the sponsor. However, these requirements will not take effect until 180 days after the guidance is finalized in June 2025. All clinical trial enrollment that takes place after the 180 days will need to comply with the new requirements. 

What Is the Diversity Action Plan?

The DAP is designed to increase enrollment from historically underrepresented groups and collect data that is more representative of the population intended to use the investigational product. In line with the FDORA Act’s goals, the draft guidance aims to ensure that sponsors not only take age, sex, racial, and ethnic demographic characteristics into account when creating their DAP, but also socioeconomic status, geographic location, disabilities, and sexual orientation. 

What Content Is Expected in the Diversity Action Plan?

• The enrollment goals for the study—these should reflect the populations in which the given disease or condition is most prevalent. 
• The rationale for the study’s enrollment goals—including any necessary background information on the disease, analysis, and potential varying effectiveness across the different populations included.
• The plans to meet the enrollment goals—this may include community engagement, language assistance, and reducing the financial burden on participants. 

When to Submit the DAP?

For drugs, sponsors must submit the DAP no later than the day of the phase 3 protocol submission. However, sponsors are encouraged to submit their DAP at the end-of-phase 2 meeting.

For medical devices, sponsors must submit the DAP with the IDE application, if the study requires it. If no IDE application is required, the DAP must be submitted as part of the device’s premarket notification (510(k)), PMA application, or De Novo classification request, as applicable.

Impact of the DAP on Clinical Trials

The new Diversity Action Plan requirement should lead to the collection of representative results. This is especially important as patients of different races and ethnicities can respond to drugs in different ways. When the demographics of trial participants don’t match that of the population affected by the disease, we cannot be certain that treatments will be safe and effective for the populations that need them. This is especially important in diseases that disproportionately affect diverse populations such as cardiovascular disease, autoimmune disease, and cancer.

How Does Medidata Support These New Requirements?

AI is a powerful tool that can both aid in setting enrollment goals and predict which sites and countries are best suited to achieve those set goals. Medidata’s diversity module helps sponsors identify sites that have historically high enrollment performance. Sponsors can select sites that are not only top enrollers but also have historically enrolled the populations of interest.

References 

• 1. 1. Commissioner, Office of the. “Diversity Action Plans to Improve Enrollment of Participants.” U.S. Food and Drug Administration, FDA, www.fda.gov/regulatory-information/search-fda-guidance-documents/diversity-action-plans-improve-enrollment-participants-underrepresented-populations-clinical-studies. Accessed 30 July 2024.