Abstract
BACKGROUND: Equality in clinical trial enrollment by sex is optimal for detecting sex-specific differences in treatment safety and efficacy. Little is known about how representation may vary among psychiatric disorders under study or interact with other clinical trial features. This study assessed sex differences in enrollment for ClinicalTrials.gov-registered psychiatric drug clinical trials and identified trial characteristics associated with enrollment disparities.
METHODS: This cross-sectional study assessed, for ten psychiatric disorders, enrollment by sex for US-based phase 1-3 interventional drug trials open to both sexes in ClinicalTrials.gov between 2000 and 2024 (441 total trials; 63,254 participants). Enrollment proportions were compared to parity (50 % each sex) and proportionality (sex-specific disease prevalence) expectations using one-sample Wilcoxon signed rank tests. Two-way ANOVA tests with interaction analyzed effects of disorder and trial characteristics on enrollment.
RESULTS: Significant (p < 0.01) female underrepresentation by both standards was detected in trials for schizophrenia (26.6 % female vs. 50.0 % sex-specific prevalence), opioid use disorder (29.2 % vs. 49.4 %), and post-traumatic stress disorder (36.2 % vs. 74.2 %). Significant male underrepresentation was noted for eating disorders (18.4 % male vs. 30.9 % sex-specific prevalence). Female enrollment improved significantly in newer trials for attention deficit hyperactivity disorder (female <2015 vs. ≥ 2015: 29.0 % vs. 53.2 %, p < 0.001) and alcohol use disorder (22.0 % vs. 37.7 %, p = 0.04).
CONCLUSIONS: Enrollment disparities by sex were observed for psychiatric drug clinical trials, with male and female participants underrepresented in different areas of research. Most disorders have not demonstrated progress toward improving representation over time. Psychiatric disorders with unequal and disproportionate enrollment may benefit from support to improve representation.