A Non-Representative Sample: Racial and Ethnic Diversity in Clinical Trials of FDA-Approved Drugs

OBJECTIVES: Given recent emphasis on clinical trial diversity by both the FDA and ICER, we sought to evaluate racial and ethnic representation in pivotal trials of FDA-approved drugs.

METHODS: Demographic data were extracted from pivotal trials for all New Drug and Biologic License Applications approved by the FDA from January 2017 through December 2022. Patient demographics were assessed as a median percentage across trials and compared to US Census Bureau 2022 population estimates, with additional subgroup analyses conducted by therapeutic area (per ICD-10 classification).

RESULTS: Across 297 FDA approvals for 293 therapies, Black, Asian, and Hispanic/Latino participants were notably underrepresented, comprising a median 4%, 5%, and 8% of pivotal trial populations, respectively, vs 13.6%, 6.3%, and 19.1% of the overall US population. These trends varied little over the time period evaluated, aside from a small uptick in Asian patients.

When demographics were assessed by therapeutic area, Black (2%-5%) and Hispanic/Latino patients (3.5%-9%) were underrepresented in nearly all categories, with the notable exception of infectious disease (18% and 15%, respectively), most commonly HIV. Asian patients were underrepresented (2.5%-4%) in approvals for endocrine and nervous system diseases but were well-represented in blood disorder approvals (9.2%).

In the subset of approvals with ≥90% white participants (n=64), most FDA reviews (59%) noted this lack of diversity, with only 27% described as consistent with the target patient population. Moreover, three recent reviews cited insufficient diversity as the rationale for requiring a post-marketing commitment. Although diversity limitations are frequently attributed to ex-US patient populations, 60% of approvals with a majority-US population (n=102) overrepresented white patients relative to the US national average (75%).

CONCLUSIONS: Appropriate racial and ethnic representation in clinical trials remains an elusive goal. Manufacturers should anticipate increasing focus on representation in both regulatory and reimbursement decisions, and adapt their clinical development programs accordingly.