Women are under-enrolled in acute stroke studies by up to 5.3 percentage points, an under-representation possibly caused by trials using strict age limit inclusion criteria, according to research findings in JAMA Neurology.

A team of researchers from the United States and Australia performed a meta-analysis of 115 phase 2 and 3 randomized clinical trials that included patients with stroke and/or transient ischemic attacks. All studies examined a treatment for stroke that started within a 1-month period of stroke onset.

In the analysis, the study investigators evaluated the enrollment disparity difference (EDD), the absolute difference between trial participants who were women and the proportion of strokes that occurred in women.


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The pooled analysis included 121,105 patients who are randomly assigned to an active intervention or placebo or other therapy. Approximately 43.4% (n=52,522) of participants in these trials were women. The study investigators noted that women were under-enrolled by approximately 5.3 percentage points, as evidenced by the random-effects summary EDD of -0.053 (95% CI, -0.065 to -0.040).

Overall, the sex disparity was observed across all geographic regions, types of interventions, and stroke types aside from subarachnoid hemorrhage (EDD, 0.117; 95% CI, 0.084-0.150).

In an analysis that excluded subarachnoid hemorrhage trials, the summary EDD was -0.067 (95% CI, -0.078 to -0.057), suggesting women were under-represented in stroke trials by 6.7 percentage points relative to the overall stroke population.

Additionally, an upper age limit of 80 years or younger as a study eligibility criterion correlated with a 6–percentage point reduction in female enrollment in a multivariable meta-regression analysis (β, -0.061; 95% CI, -0.099 to -0.023).

This study may have been limited by its meta-regression model due to the potential for residual confounding at the patient or trial level.

While “further research is needed to understand the causes of the [under-enrollment] of women in acute stroke trials,” the study investigators concluded that “authors imposing an upper age limit as an eligibility criterion should provide a clear rationale for doing so.”

Reference

Strong B, Pudar J, Thrift AG, et al. Sex disparities in enrollment in recent randomized clinical trials of acute stroke: A meta-analysis. Published online April 26, 2021. JAMA Neurol. doi:10.1001/jamaneurol.2021.0873