Evaluating sex as a biological variable in preclinical research: The devil in the details

Abstract

Translating policy into action is a complex task, with much debate surrounding the process whereby US and Canadian health funding agencies intend to integrate sex and gender science as an integral component of methodological rigor and reporting in health research. Effective January 25, 2016, the US National Institutes of Health implemented a policy that expects scientists to account for the possible role of sex as a biological variable (SABV) in vertebrate animal and human studies. Applicants for NIH-funded research and career development awards will be asked to explain how they plan to factor consideration of SABV into their research design, analysis, and reporting; strong justification will be required for proposing single-sex studies. The Canadian Institutes of Health Research is revising their peer review accreditation process to ensure that peer reviewers are skilled in applying a critical lens to protocols that should be incorporating sex and gender science. The current paper outlines the components that peer reviewers in North America will be asked to assess when considering whether SABV is appropriately integrated into research designs, analyses, and reporting. Consensus argues against narrowly defining rules of engagement in applying SABV, with criteria provided for reviewers as guidance only. Scores will not be given for each criterion; applications will be judged on the overall merit of scientific innovation, rigor, reproducibility, and potential impact.