Sex Disparity in Enrolment to Clinical Trials for Onchocerciasis and Trachoma

To determine whether female enrolment in randomized interventional clinical trials for onchocerciasis and trachoma reflects the real-world sex distribution of disease burden, and to evaluate sex-based differences across trial characteristics.

We performed a cross-sectional analysis of completed randomized interventional clinical trials registered on ClinicalTrials.gov evaluating onchocerciasis or trachoma and initiated between 1974 and 2020. Eligible trials used double masking or greater and reported results through ClinicalTrials.gov or peer-reviewed publication. Female representation was assessed using population-to-prevalence ratios (PPRs), calculated as the proportion of female trial participants divided by the proportion of females in the real-world disease population using Global Burden of Disease estimates. A PPR of 0.8-1.2 indicated adequate representation. Secondary analyses examined representation by disease type, intervention category, study phase, masking, and sponsor location.

A total of 103 trials including 327,468 participants were analysed (42 onchocerciasis, 61 trachoma). Overall female enrolment was slightly lower than expected (PPR 0.88; 95% confidence interval [CI] 0.80-0.96). Trachoma trials demonstrated equitable representation (PPR 1.06; 95% CI 0.98-1.13), whereas onchocerciasis trials showed substantial underrepresentation (PPR 0.62; 95% CI 0.49-0.76), with 29% enrolling no female participants. Drug-based interventions (PPR 0.79) and phase II trials (PPR 0.44) most frequently under-enrolled women, while surgical trials overrepresented women (PPR 1.40).

Women were substantially underrepresented in onchocerciasis trials despite balanced enrolment in trachoma trials, highlighting the need for improved sex-disaggregated reporting and equitable recruitment in clinical trials for neglected tropical eye diseases.