Women now account for roughly half of all participants in NIH-supported clinical research, which is subject to NIH's Policy on the Inclusion of Women in Clinical Research. However, more often than not, basic and preclinical biomedical research has focused on male animals and cells. An over-reliance on male animals and cells may obscure understanding of key sex influences on health processes and outcomes.
Accounting for sex as a biological variable begins with the development of research questions and study design. It also includes data collection and analysis of results, as well as reporting of findings. Consideration of sex may be critical to the interpretation, validation, and generalizability of research findings. Adequate consideration of both sexes in experiments and disaggregation of data by sex allows for sex-based comparisons and may inform clinical interventions. Appropriate analysis and transparent reporting of data by sex may therefore enhance the rigor and applicability of preclinical biomedical research.
NIH expects that sex as a biological variable will be factored into research designs, analyses, and reporting in vertebrate animal and human studies. Strong justification from the scientific literature, preliminary data, or other relevant considerations must be provided for applications proposing to study only one sex. Investigators are strongly encouraged to discuss these issues with NIH program staff prior to submission of applications. Further information regarding NIH expectations for the consideration of sex as a biological variable is provided in this guidance document (PDF - 74.6KB).
The 4 Cs of Studying Sex to Strengthen Science
- Consideration of Relevant Biological Variables in NIH Grant Applications
- Considering sex as a biological variable in preclinical research, (PDF - 791.3KB) September 28, 2016
- FAQs on Consideration of Relevant Biological Variables, Such as Sex
- Highlights of NIH Women's Health and Sex Differences Research, 1990–2010 (PDF - 1.6MB) (PDF - 1.6MB)
- Monitoring the Implementation of the National Institutes of Health Strategic Plan for Women's Health and Sex/Gender Differences Research: Strategies and Successes (PDF - 3.8MB) (PDF - 3.8MB)
- NHLBI Sex Bias in Cardiovascular Research Working Group Executive Summary, September 22, 2014
- NIH's Policy on the Inclusion of Women and Minorities in Clinical Research
- NIH Rigor and Reproducibility Web Portal
- Reproducibility Issues in Research with Animals and Animal Models: Workshop in Brief
- Research Reporting Guidelines and Initiatives: By Organization (SAGER Guidelines)
- Sex-Specific Reporting of Scientific Research
- Studying Both Sexes: A Guiding Principle for Biomedicine
- What Does It Mean to Consider Sex as a Relevant Biological Variable in Your NIH Grant Application?