Sex Representation in US Stroke Clinical Trials: A Decade of Trends and Challenges

Stroke remains a major cause of disability and mortality in the US, with significant sex-based disparities, and females remain underrepresented in stroke clinical trials. We aimed to examine sex representation in US-based stroke clinical trials, identify trial characteristics associated with higher female enrollment (≥ 50%), and explore factors influencing recruitment strategies.

This mixed-methods study analyzed US-based stroke clinical trials registered on ClinicalTrials.gov between January 1, 2010 and December 31, 2020. A thematic analysis of recruitment strategies and eligibility criteria was conducted for trials with ≥ 50% female enrollment. We examined the proportion of female participants enrolled in each trial and trial characteristics, including funding source, principal investigator sex, participant age, and recruitment strategies.

Of 456 eligible trials, only 102 (22%) enrolled ≥ 50% female participants. Compared with trials with < 50% female enrollment, these trials more often included both sexes (99.0% vs. 65.5%) and enrolled a greater median number of female participants (22.5 vs. 10). Female-led studies were more common among trials with higher female representation (40.2% vs. 37.6%). Qualitative analysis revealed that broader inclusion criteria, hybrid recruitment strategies (e.g., combining hospital outreach), and targeted accommodations for stroke-related disability were associated with higher female enrollment. Common barriers included exclusionary eligibility criteria, logistical challenges (e.g., transportation), and language limitations.

Inclusive design, community-engaged recruitment, and structural accommodations including support for sex-based roles like caregiving are potentially influential in promoting equitable participation. Addressing sex disparities in stroke research is essential for improving the relevance, effectiveness, and fairness of stroke interventions in clinical practice.