Objectives: Sex is a critical biological variable influencing pharmacokinetics and pharmacodynamics.While global initiatives like the Sex as a Biological Variable policy of the U.S. National Institute of Health which aims to enhance sex inclusivity, Phase 1 trials often exclude women due to safety concerns.This study quantitatively evaluates sex representation in Korean Phase 1 trials compared to global trends.Methods: All clinical trials initiated between 2004 and 2023 were retrieved from ClinicalTrials.gov using the public application programming interface.Studies were categorized as Global or Korea and classified by phase (Phase 1-4).We assessed protocol-defined eligibility criteria, pooled female participation rates, and target conditions.Trends in recruitment patterns and discrepancies between initiated and results-posted studies were examined.Findings: In Phases 2-4, trials predominantly enrolled participants of all sexes (>90%) both globally and in Korea, with female participation rates near 50%.In contrast, Phase 1 trials in Korea demonstrated a marked male predominance.While globally maleonly Phase 1 trials remained stable at 10%-15%, they frequently exceeded 40%-50% in Korea.Actual female enrollment in Korean Phase 1 trials was consistently lower and more variable than the global average (~40%).This disparity was largely driven by healthy volunteer studies, which accounted for approximately half of male-only trials in Korea.Although sex data were reliably reported when results were posted, the overall rate of result reporting in Korean Phase 1 trials was low.Conclusions: While Korean clinical trials have achieved quantitative growth and secured sex diversity comparable to global standards in late phase trials (Phases 2-4), a male-centric composition persists in Phase 1 clinical trials.To enhance the generalizability of data across all potential patient populations, continuous institutional improvements and sustained attention are required to encourage the inclusion of diverse demographic groups, starting from early phase studies.
Seonghae Yoon (2026) studied this question.