Importance of Sex and Gender Differences in Enrollment and Interpretation of Stroke Clinical Trials.

OBJECTIVES: This review aims to reinforce the importance of improving sex balance in preclinical trials and sex and gender diversity and proportional balance in clinical trials enrollment and how this influences interpretation of stroke clinical trials. It also aims to identify strategies for improvement in data collection.

MATERIALS AND METHODS: A PubMed search was conducted of publications in English, using MeSH terms sex, sex characteristics, gender identity, transgender, gender-nonconforming persons, clinical trials as topic, stroke. Of 249 search results, 217 were human or animal studies related to stroke, the majority of which were reviews, secondary analyses of stroke clinical trials, meta analyses, or retrospective studies, subject to the methods of sex and gender acquisition per the primary data source. Articles were reviewed, noting inclusion or absence of sex and gender definitions and trial design. Selected articles were supplemented with United States Food and Drug Administration, National Institutes of Health, and National Academy of Science, Engineering, and Medicine publications.

RESULTS: The majority of preclinical studies continue to report sex as a binary variable, and the majority of stroke clinical trials report sex and gender as interchangeable and binary. Mindful trial design and statistical analysis can improve accuracy in the interpretation of sex and gender differences. Guidance exists to improve reporting on currently accepted sex and gender definitions, recommended data collection instruments, and appropriate statistical analyses.

CONCLUSIONS: Despite acknowledgement of having failed to achieve diverse and proportionally balanced enrollment, sex and gender imbalance across the research continuum remains prevalent. Responsible incorporation of sex and gender in stroke clinical trials can be achieved through thoughtful study design, use of contemporary sex and gender definitions, inclusive prospective data collection, balanced enrollment with prespecified goals, and appropriate statistical analysis.