Clinical trial diversity: Sponsors seek clarity on data sources, timing

Drugmakers and clinician organizations praised the US Food and Drug Administration’s (FDA) recent draft guidance containing recommendations on developing a Race and Ethnicity Diversity Plan to improve enrollment of underrepresented racial and ethnic groups in clinical trials. But in public comments, they also called for greater details on the types of data that should be used to assess adequate enrollment of these populations, how these diversity plans should be applied to global clinical trials and more specifics on the timing of plan submissions and updates.
 
FDA issued the draft guidance in April 2022, recommending that sponsors submit a Race and Ethnicity Diversity Plan with investigational new drug (IND), biologics license application (BLA), and investigational device exemption (IDE) submissions. (RELATED: FDA recommends sponsors plan to include race, ethnicity in clinical trial design, Regulatory Focus 13 April 2022)
 
Data sources
 
The draft guidance advises sponsors to begin with an assessment of any data indicating the potential for a product to have “differential safety or effectiveness associated with race or ethnicity.” However, drugmakers commented on the need for more clarity on the types of data that should be used. “It is not clear what ‘any data’ is meant to include. For example, does this refer to data on potential differences in drug safety and effectiveness associated with race and ethnicity due to biological factors only, or is the intent to include data on any differences, including those due to behavioral or environmental factors?” Pfizer wrote in comments on the draft guidance.
 
Amgen asked FDA for examples of disease areas where race and ethnicity are known to impact the safety and effectiveness of drugs and examples of disease-specific benchmarks of race and ethnicity distribution. “This information could also help promote a more consistent diversity strategy among sponsors which would reduce potential operational bias in evaluating the benefit-risk assessment within the therapeutic area and drug class,” Amgen commented.
 
The Association of Clinical Research Organizations (ACRO) called on FDA to clarify the types of real-world data that can be used in setting enrollment goals. “Real-world data is not always complete, especially for race and ethnicity. It will be important for the FDA to advocate for completeness of real-world datasets,” the organization noted.
 
The Cleveland Clinic suggested that FDA consider the use of genetic ancestry estimation to help characterize the differential effects of medical products, rather than self-report of race and ethnicity alone. In terms of determining enrollment goals, the Cleveland Clinics asked FDA to clarify those goals will be defined by a particular geography or the United States in general.
 
The Association of Community Cancer Centers (ACCC) Community Oncology Research Institute commented that FDA should explicitly recommend that sponsors collect social determinants of health (SDOH) data as part of the Diversity Plan. “Given the significant impact of SDOH on outcomes and efficacy and the barriers that these social factors may create in underrepresented racial and ethnic populations, we feel strongly that sponsors should address SDOH in their Plans and make efforts to document social needs data throughout the development life cycle of the medical product,” commented Randall A. Oyer, MD, chair of the ACCC Community Oncology Research Institute Task Force.
 
Timing
 
Commenters also raised concerns about the ability of sponsors to have the Diversity Plan ready at the End of Phase 2 (EOP2) meeting. Amgen noted that it makes sense to discuss some elements of the Diversity Plan at the EOP2 meeting but that some part of the phase 3 program, including feasibility and site selection, may not be completed until later.
 
The Biotechnology Innovation Organization (BIO) also commented on the need for clear expectations on what information should be submitted at various stages of development and when and how updates should be made to the diversity plan. BIO also asked for information on the review duration of the plan and its location within the dossier.
 
Global clinical trials
 
Drug makers asked for more information about how the diversity plan recommendations, which refer to underrepresentation of racial and ethnic groups in the US population, would be applied in the context of global clinical trials. Pfizer commented that the draft guidance does not explicitly state if the diversity plan should focus on US data or global data. BIO recommended that FDA convene public meetings with industry and other to discuss the best practices for recruiting, enrolling, and retaining diverse patient populations in global clinical trials.
 
Public comments on draft diversity plan guidance