Sex as a Biological Variable: A 5-Year Progress Report and Call to Action

Abstract

A little over 5 years ago, the U.S. National Institutes of Health (NIH) announced the intention to develop policies to require applicants to report plans to balance male and female cells and animals in preclinical investigations. Soon thereafter, the NIH issued a request for information from the scientific community and consulted with various stakeholders. The feedback received was considered during development of policy requiring the consideration of sex as a biological variable (SABV) in NIH-funded research on vertebrate animals and humans, which went into effect for applications due on or after January 25, 2016. We identified NIH programs related to SABV and reviewed SABV-relevant scientific literature. We find that the application of SABV throughout the research process can serve as a guiding principle to improve the value of biomedical science. The NIH is engaged in ongoing efforts to develop resources to help investigators consider SABV in their research. We also provide an update on lessons learned, highlight ways that different disciplines consider SABV, and describe the opportunities for scientific discovery that applying SABV offers. We call on NIH's various stakeholders to redouble their efforts to integrate SABV throughout the biomedical research enterprise. Sex- and gender-aware investigations are critical to the conduct of rigorous and transparent science and the advancement of personalized medicine. This kind of research achieves its greatest potential when sex and gender considerations are integrated into the biomedical research enterprise in an end-to-end manner, from basic and preclinical investigations, through translational and clinical research, to improved health care delivery.

Keywords: National Institutes of Health; clinical trial; gender; personalized medicine; policy; preclinical research; sex as a biological variable; women's health.