Sex Representation in U.S. Clinical Trials: A Statistical Benchmarking Study

Background Sex equity in clinical research is essential for generalizable and safe medical care. Historical underrepresentation of women in trials has prompted decades of policy reform. Whether these reforms have succeeded remains inadequately assessed with statistical rigor. Methods We analyzed 1,825 U.S.-based clinical trials registered between 2000 and 2024 using ClinicalTrials.gov data. Trials were classified by sex inclusion criteria and therapeutic area. Chi-square tests were applied to assess deviation from expected female representation (50.8%) based on national demographic data. Trends across three periods (2000–2009, 2010–2018, 2019–2024) were also analyzed. Results Overall, 50.1% of trials included female participants—statistically indistinguishable from the expected 50.8% (p = 0.844). No therapeutic category showed a significant deviation. Temporal analysis revealed consistent improvement: inclusion rates rose from 92.8% in 2000–2009 to 98.8% in 2019–2024 (p = 0.0014). Conclusions Sex representation in U.S. clinical trial design now matches population expectations, indicating successful policy implementation. However, design equity does not guarantee equity in enrollment or outcome analysis. Further work is needed to translate design inclusion into participant-level and analytical equity.