Survey Highlights Need for More FDA Clarity on Clinical Trial Diversity Plans

By Tanvi Mehta

A new ELIQUENT Life Sciences survey of biopharmaceutical companies shows that drug developers are stepping up efforts to increase clinical trial diversity, but they need more guidance and clarity from the U.S. Food and Drug Administration (FDA) to navigate the significant challenges—in the U.S. and globally—to achieving diversity goals.

Initial efforts show promise

The qualitative survey, funded by Eli Lilly and Company, included 12 biopharmaceutical companies and was designed to assess companies’ actions, experiences, and progress during the initial stage of planning and implementation of U.S. Diversity Plans. Conducted in the fourth quarter of 2023, survey responses were based on companies’ early experience with the 2022 FDA Draft Guidance[1]. Participants included large, medium, and smaller companies, based on 2022 annual revenue.

All surveyed companies reported positive progress in developing their diversity plans:

• All but one had submitted at least one plan to FDA.
• All 12 had already created and executed diversity plans – primarily for pivotal trials, but in some cases for earlier-phase studies, as well.
• Eleven of the 12 surveyed have created a dedicated team that focuses on diversity goals for the company’s clinical trials and guides product teams on plan development.
• Companies reported incorporating a variety of methods to make studies more accessible for patients, more reflective of real-world conditions, and enable more diverse participation. Community engagement, educational efforts, and expanding the use of community-based (decentralized) trials to reach and facilitate enrollment of individuals who have traditionally been underrepresented in clinical trials were described as  cornerstones of company efforts.

Uncertainty remains

Despite progress, as companies develop and submit diversity plans to FDA, they face significant uncertainties that limit their ability to set goals and enroll diverse participants. These arise from factors that include ambiguity on acceptable methodologies and data sources. Specifically,  the survey revealed 3 major concerns:

• Diversity enrollment goals are meant to apply to the U.S. market, based on U.S. disease prevalence and incidence rates.  Yet, most development programs are global and integrating these goals with data collection in global settings is difficult. For example, disease prevalence and incidence data are not systematically gathered in all countries.
• Assessment of diversity is complicated by the lack of harmonization in how race and ethnicity are defined. The U.S. Office of Management and Budget (OMB) definitions – which FDA follows – do not always translate effectively to other countries’ populations and in some cases may even be challenging to apply even in the U.S.
• Regulatory consequences of not meeting diversity goals are unknown. Given that methods for increasing trial diversity (from innovative study designs to new types of recruitment efforts) are in early stages of testing, the chances of meeting a stated diversity goal remain unknown.  Similarly, as learning about how to meet them well evolves,  there is the potential for sponsors to be unable to achieve set diversity goals despite best efforts. Companies surveyed said that lack of clarity on how FDA will respond when this occurs is concerning. They cited further concerns that any post-marketing data collection effort in follow-up could result in the same missed goals, calling into question whether meeting some goals may not be feasible to achieve.

What’s needed from regulators: A path forward

The survey findings confirm the need for engagement with and clarity from FDA to address these and other uncertainties based on experience to date.  Key areas cited that require more clear, consistent guidance were:

• How data from diverse patients outside of the United States can be used to meet U.S. trial diversity goals. Those surveyed reported that FDA feedback has been inconsistent across its divisions (and even within divisions) regarding the applicability of global diversity data to meeting U.S. diversity goals.
• The methodologies and data sources FDA will allow for setting diversity goals. Companies noted many resources they currently use (e.g., Surveillance, Epidemiology, and End Results (SEER) Program, various sources of real-world evidence (RWE)) but cited a lack of clarity on which sources are acceptable and to what extent.
• The need for global harmonization of approaches to the collection of representative patient data. Sponsors surveyed called for consistent definitions of race and ethnicity across countries. They also cited the need for regulators to acknowledge the challenges of setting diversity goals due to the lack of epidemiological data available in some countries.

Since the survey was conducted, FDA updated the Diversity Action Plan Draft Guidance[2] on June 26, 2024. Companies are now assessing the latest guidance to determine whether (or to what extent) their concerns have been addressed.

On a positive note, the companies surveyed described the positive impact of FDA’s Diversity Plans Draft Guidance[3] on their clinical trial enrollment efforts, expressing that it has resulted in more attention and focus on the recruitment process among teams and within their companies overall. While it has brought focus to obstacles to ensuring representativeness in clinical trials,  in addition to guidance from regulators, these may best be addressed through collaborations among clinical trial stakeholders.