IMPORTANCEThe underenrollment of women in randomized clinical trials represents a threat to the validity of the evidence supporting clinical guidelines and potential disparities in access to novel treatments. OBJECTIVE To determine whether women were underenrolled in contemporary randomized clinical trials of acute stroke therapies published in 9 major journals after accounting for their representation in underlying stroke populations.DATA SOURCES MEDLINE was searched for acute stroke therapeutic trials published between January 1, 2010, and June 11, 2020.STUDY SELECTION Eligible articles reported the results of a phase 2 or 3 randomized clinical trial that enrolled patients with stroke and/or transient ischemic attack and examined a therapeutic intervention initiated within 1 month of onset.DATA EXTRACTION Data extraction was performed by 2 independent authors in duplicate. Individual trials were matched to estimates of the proportion of women in underlying stroke populations using the Global Burden of Disease database. MAIN OUTCOMES AND MEASURESThe primary outcome was the enrollment disparity difference (EDD), the absolute difference between the proportion of trial participants who were women and the proportion of strokes in the underlying disease populations that occurred in women. Random-effects meta-analyses of the EDD were performed, and multivariable metaregression was used to explore the associations of trial eligibility criteria with disparity estimates. RESULTSThe search returned 1529 results, and 115 trials (7.5%) met inclusion criteria. Of 121 105 randomized patients for whom sex was reported, 52 522 (43.4%) were women. The random-effects summary EDD was −0.053 (95% CI, −0.065 to −0.040), indicating that women were underenrolled by 5.3 percentage points. This disparity persisted across virtually all geographic regions, intervention types, and stroke types, apart from subarachnoid hemorrhage (0.117 [95% CI, 0.084 to 0.150]). When subarachnoid hemorrhage trials were excluded, the summary EDD was −0.067 (95% CI, −0.078 to −0.057). In the multivariable metaregression analysis, an upper age limit of 80 years as an eligibility criterion was associated with a 6-percentage point decrease in the enrollment of women.CONCLUSIONS AND RELEVANCE Further research is needed to understand the causes of the underenrollment of women in acute stroke trials. However, to maximize representation, investigators should avoid imposing age limits on enrollment.

Background and Purpose: When reporting primary results from randomized controlled trials, recommendations include reporting results by sex. We reviewed the reporting of results by sex in contemporary acute stroke randomized controlled trials. Methods: We searched MEDLINE for articles reporting the primary results of phase 2 or 3 stroke randomized controlled trials published between 2010 and June 2020 in one of nine major clinical journals. Eligible trials were restricted to those with a therapeutic intervention initiated within one month of stroke onset. Of primary interest was the reporting of results by sex for the primary outcome. We performed bivariate analyses using Fisher exact tests to identify study-level factors associated with reporting by sex and investigated temporal trends using an exact test for trend. Results: Of the 115 studies identified, primary results were reported by sex in 37% (n=42). Reporting varied significantly by journal, with the New England Journal of Medicine (61%) and Lancet journals (40%) having the highest rates ( P =0.03). Reporting also differed significantly by geographic region (21% Europe versus 48% Americas, P =0.03), trial phase (13% phase 2 versus 40% phase 3, P =0.05), and sample size (24% <250 participants versus 61% >750 participants, P <0.01). Although not statistically significant ( P =0.11), there was a temporal trend in favor of greater reporting among later publications (25% 2010–2012 versus 48% 2019–2020). Conclusions: Although reporting of primary trial results by sex improved from 2010 to 2020, the prevalence of reporting in major journals is still low. Further efforts are required to encourage journals and authors to comply with current reporting recommendations.

Introduction: When reporting primary results, it is recommended that RCTs report sex-specific outcomes. We reviewed the reporting of sex-specific outcomes in contemporary acute stroke RCTs. Methods: We searched MEDLINE for manuscripts published between 2010 and June 2020 in one of nine major clinical journals reporting the primary results of phase 2 or 3 stroke RCTs. Eligible trials tested a therapeutic intervention initiated within one month of stroke onset. Reporting of sex-specific primary results was the outcome of interest. We also investigated whether the trial formally tested for an interaction between sex and treatment and if that interaction test was statistically significant. We performed bivariate analyses using Fisher’s exact tests to identify study-level factors associated with sex-specific reporting including journal, geographic region, trial phase, sample size, stroke type, trial type (e.g. thrombolytic, EVT, secondary prevention), and industry funding. Temporal trends using two-year time periods were also explored. Results: Of the 115 studies identified, sex-specific primary outcome data were reported in 37% (n=42). Reporting varied significantly by journal, with NEJM (61%) and Lancet journals (40%) having the highest rates (p=0.03) (Table). Reporting also differed by geographic region (p=0.03), trial phase (p=0.05), and sample size (p<0.01). Reporting did not vary significantly by stroke type, trial type, or industry involvement. While not significant, there was a positive temporal trend in favor of greater reporting in later publications (p=0.09). Of the 29 trials that formally tested for an interaction between sex and treatment, only one significant interaction was found. Conclusions: Although reporting of sex-specific outcomes improved from 2010 to 2020, the prevalence of reporting in major journals is still low. Further efforts are required to ensure that journals and authors comply with reporting guidelines.

Introduction: The inadequate enrollment of women in RCTs represents a threat to trial generalizability and potential inequities in access to novel treatments. We sought to determine whether women were under-enrolled in contemporary acute stroke trials. Methods: We searched MEDLINE for completed RCTs published in one of nine major journals between 2010 and 2020. Eligible studies were phase 2 or 3 trials undertaken to test therapeutic interventions within one month of stroke onset. For each trial we calculated the proportion of trial participants that were women (PPW). We used Global Burden of Disease (GBD) data to estimate the expected proportion of strokes occurring in women in the underlying stroke populations (PSW). We matched individual estimates from the GBD data to each trial based on geographic location, year, and stroke type. To quantify disparities, we calculated the enrollment disparity difference (EDD), defined as EDD = PSW - PPW. A positive EDD indicates that women were under-represented in the trial. We used random effects meta-analysis to pool individual EDDs and conducted subgroup analyses. Results: We identified 115 trials that met eligibility criteria. The random effects summary EDD was 0.053 (95% CI = 0.040, 0.053), indicating that women were under-enrolled in acute stroke trials by 5% relative to their representation in the underlying stroke population. However, there was substantial between-trial variability in the EDD (I 2 =84.4%). In subgroup analyses, the EDD was similar across subgroups except for stroke type (figure); trials that only included subarachnoid hemorrhages enrolled women in excess of their representation in the underlying population (summary EDD = -0.117 [95% CI = -0.150, -0.084]). Conclusions: Overall, women were modestly under-represented in contemporary acute stroke trials compared to their representation among all strokes. Further study is needed to elucidate factors driving sex differences in enrollment between RCTs.