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Considering sex as a biological variable in research design, data analyses and reporting



Jelstrom, Eve; Matthews, Abigail G; Shmueli-Blumberg, Dikla; Lindblad, Robert; Van Veldhuisen, Paul; Rosa, Carmen

SCT Annual Meeting

Liverpool, UK


Statistical Analysis Trial Management & Research Coordination Outcomes

In January 2016, a new National Institutes of Health (NIH) policy went into effect requiring that researchers consider sex as a biological variable in animal and human studies (see NOT-OT-15-102 Guidance). This requires grant applicants of NIH-funded research studies to explain how sex will be factored into research design, data analyses and reporting, requiring strong justification for studying only one sex. The policy is meant to increase the quality and generalizability of biomedical research, thus enhancing the reproducibility and translatability of research in the biomedical field. We will present best practices for implementation of sex as a biological variable in the various phases of a clinical trial, and will include examples from the National Institute on Drug Abuse (NIDA)-funded grants. The first step in implementation involves a rigorous literature review that would explain how sex may influence the study design based on previous preclinical or clinical research. If there is a reasonable foundation of existing research, sex-specific hypotheses could be generated, including primary, secondary or exploratory hypotheses. The next step entails developing a study design, which should include a statistical analysis plan that provides for subgroup analyses identifying differences in the intervention effect by sex. Such subgroup analyses should be implemented using interaction models to test whether the treatment effect differs across sexes, or an analogous approach if there is no modeling. Recognizing that most clinical trials are not powered to detect differences based on gender, these analyses are exploratory in nature. In progress reports and publications, the study findings should include whether sex differences were, or were not, detected. Grantees are also required to report annually on the enrollment of males and females so that this can be monitored throughout the implementation of the trial. This new policy guides researchers to take into account whether there are biological factors related to sex which should be explored in the study design or approached differently than originally planned. The NIH policy will have an impact on the planning and the conduct of clinical trials in humans and potentially new relationships between disease entities and sex will be explored and given more weight.

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