Representation of Women in Stroke Clinical Trials: A Review of 281 Trials Involving Over 500,000 Participants

Background and Aim: Women have been under-represented in clinical trials areas of cardiovascular disease but there is less certainty over the level of disparity specifically in stroke and whether there is any influence of pathological subtype, age and time. We examined the participation of women in trials according to stroke prevalence in the population. Methods: Randomized controlled trials with ≥100 participants enrolled between 1990 and 2020 identified from ClinicalTrials.gov, using keywords “stroke” and “cerebrovascular accidents”, and subsequently published (identified using PubMed, Google Scholar, and Scopus) were included. To quantify sex disparites in enrolment we calculate the participation to prevalence ratio (PPR), defined as the percentage of women participating in a trial against the prevalence of women in the disease population. Results: There were 281 stroke trials eligible for analyses with a total of 588,887 participants, of whom 37.4 % were women. Overall, women were represented at a lower proportion relative to their prevalence in the underlying population (mean PPR 0.84; 95% confidence interval [CI] (0.81 to 0.87)). The greatest differences were observed in trials of hemorrhagic stroke (PPR 0.73; 95% CI 0.71 to 0.74), trials with a mean age of participants <70 years (PPR 0.81; 95% CI (0.78 to 0.84)), non-acute interventions (PPR 0.80; 95% CI (0.76 to 0.84)) and rehabilitation trials (PPR 0.77; 95% CI 0.71 to 0.83)). For 77% of trials, participation was lower than the prevalence of stroke in the population (i.e. PPR <1.0). These findings did not significantly change over the period from 1990 to 2020 (p for trend = 0.201). Conclusion: Women are disproportionately represented in stroke trials relative to the burden of disease in the population. Clear guidance and effective implementation strategies are required to improve the inclusion of women and thus broader knowledge of the impact of interventions in clinical trials. Funding: None to declare Declaration of Interest: ECS reports receiving fees for speaking at seminars for Bayer and Novartis. CSA reports receiving speaker fees and research grants from Takeda China. MW is a consultant for Amgen CC acknowledges the support of the National Heart Foundation of Australia (Postdoctoral fellowship 102741). SAEP is supported by a UK Medical Research Council Skills Development Fellowship (MR/P014550/1). CSA holds a Senior Investigator Fellowship of the National Health and Medical Research Council (NHMRC) of Australia.