Post-traumatic stress disorder (PTSD) randomized clinical trials: predicting sex differences in enrollment patterns.

BACKGROUND

Equality in clinical trial enrollment by sex is important for detecting sex-specific differences in treatment safety and efficacy. This study analyzed sex differences in enrollment for Post-traumatic Stress Disorder (PTSD) randomized controlled clinical trials (RCTs) to determine the contexts in which enrollment disparities are most pronounced and inform strategies to improve equitable representation in future PTSD clinical trials.

METHODS

Data were obtained from the PTSD Repository, which encompasses all US-based and international RCTs published across a 36-year period between January 1, 1988 and April 1, 2024. One-sample Wilcoxon signed rank tests compared the median sex composition of RCT enrollment to that of U.S. PTSD cases and tested whether median deviation from sex parity in enrollment (50% each sex) differed from zero. Hierarchical multiple regression models predicted female enrollment proportion and deviation from sex parity based on trial characteristics including location, timing, size, eligibility criteria, and intervention.

RESULTS

Across all 527 PTSD RCTs encompassing 47,699 participants (44.9% female), median female enrollment was consistently lower than population-based expectations (53.0% female [95% CI: 44.1%-57.5%] vs. 74.2% expected). Lower female enrollment was predicted by requirement of active military or veteran-only status at all trial sites (B=-60.60, β=-0.810, p < 0.001), inclusion of comorbid substance use disorder (B=-9.42, β=-0.117, p = 0.002), and pharmacotherapy (B=-10.58, β=-0.137, p < 0.001). Only 12.7% of all PTSD RCTs enrolled between 40 and 60% of each sex.

CONCLUSIONS

Female patients are under-enrolled in PTSD RCTs compared to population-based expectations. Eligibility criteria emphasizing male-dominant subpopulations (e.g., military cohorts, comorbid substance use) appear to contribute to these disparities.