Racial, ethnic, gender and age representation of clinical trials supporting FDA approval of cancer therapies

Abstract Background Pivotal clinical trials provide the primary evidence base for US FDA oncology drug approvals; however, persistent demographic imbalances in trial enrollment may compromise generalizability and exacerbate inequities in cancer care. We quantified disparities in the representation of women, racial and ethnic minority groups, and older adults in pivotal trials supporting FDA oncology approvals and evaluated trial-level characteristics associated with underrepresentation. Methods We identified pivotal trials underpinning US FDA oncology drug approvals between January 2018 and February 2026 using the FDA Hematology/Oncology Approvals database. Demographic information on sex, race, ethnicity, and age was abstracted from published trial reports and registry entries. For each subgroup, we quantified representativeness using enrollment incidence ratios (EIRs), defined as the ratio of the subgroup’s share in the trial to its share of SEER incidence (EIR < 1 indicating underrepresentation). We pooled log-transformed EIRs with random-effects models and used meta-regression to examine time trends and trial-level factors associated with disparities. We additionally conducted stratified analyses by pediatric status, accelerated approval, and other trial characteristics. Results Among 372 pivotal trials supporting US FDA oncology drug approvals (2018–2026), women, older adults, Black, and Hispanic individuals remained underrepresented relative to US cancer incidence. Pooled EIRs showed underenrollment of women (EIR, 0.92; 95% CI, 0.88–0.95), Black participants (EIR, 0.25; 95% CI, 0.21–0.28), Hispanic participants (EIR, 0.51; 95% CI, 0.45–0.58), and older adults (≥ 65 years) (EIR, 0.67; 95% CI, 0.61–0.73). Meta-regression suggested a modest increase in female representation over time (β = 0.02, p = 0.03), with no significant temporal improvement for Black or Hispanic participants. Older adult representation declined slightly. Trial-level correlates of underrepresentation included industry sponsorship, use of overall survival as the primary endpoint, and accelerated approval designation. Conclusions Despite recent regulatory initiatives, substantial demographic imbalances persist in pivotal oncology trials supporting FDA approvals. Women, Black and Hispanic individuals, and older adults remain underrepresented, potentially limiting the generalizability of efficacy and safety evidence to real-world cancer populations. Strengthened, accountable approaches—spanning more inclusive eligibility criteria and site selection, targeted recruitment, and enforceable diversity requirements—are needed to ensure equitable evidence generation in oncology drug development.