Considering sex as a biological variable; new NIH requirement effective Jan. 2016

Women comprise slightly more than half of the population–and their representation is relatively well balanced in NIH-sponsored clinical research, where they now account for roughly half of all participants. But this shift has not occurred in the preclinical realm. Today, most NIH-sponsored animal studies are focused on males, and many investigators do not report on the sex of the subjects from whom cells are obtained for cell line work. This lack of balance may obscure key sex differences and lead to confusing and  irreproducible results.

In order to address this imbalance, the NIH announced plans in May 2014 to adopt a new policy requiring a deliberate approach to the consideration of sex as a biological variable in preclinical research. Later in the year, a Request for Information went out to the research community seeking input on areas of science with the greatest opportunity or need for this consideration, the main impediments to implementation, how considering sex as a biological variable might affect reproducibility or generalizability of research, and how NIH could best facilitate sex as a biological variable in NIH-supported research. Response affirmed the need for such consideration, but most respondents expressed concern about practical aspects such as costs and constraints on methodology or experimental design. We surmise there must have been many comments to accommodate, since the full notice was released 7 months later than planned.

Last week, the full notice finally arrived, announcing NIH’s expectations that scientists now account for the possible role of sex as a biological variable in animal and human studies. Once the Office of Extramural Research’s updates are approved by the Office of Management and Budget, applications submitted for the January 25, 2016 due date and thereafter must include such consideration. Expectations include:

  • Sex as a biological variable will be factored into research designs, analyses, and reporting in vertebrate animal and human studies.
  • Strong justification must be provided for applications proposing to study only one sex.

Additional guidance can be found here, and you can read commentary on this new requirement here.