In 2014, NIH announced plans for policy changes to ensure that NIH-supported investigators consider relevant measures, including sex as a biological variable (SABV), in preclinical research. NIH solicited feedback through a request for information, and we invited the research community to participate in workshops and resource development. These activities led to new guidelines for addressing SABV as an aspect of rigor and reproducibility in NIH research project grant applications and mentored career development award applications due January 25, 2016, and beyond.
As you prepare applications and think about addressing the new instructions we wanted to offer some reminders about the policy’s origin, and about the application and review information. In particular, we wanted to point out what including SABV does not mean.
Dr. Janine Clayton, Director of the NIH Office of Research on Women’s Health, just published an article in The FASEB Journal that provides background and additional detail about the policy and its goals. The article clears up some potential misunderstandings. We have heard concerns about needs to double the numbers of animals used or to reduce project aims to accommodate additional costs. Others have interpreted the policy to mean that NIH is now mandating all experiments to be powered for both sexes. Not so. To quote from Dr. Clayton’s article:
In its efforts to enhance reproducibility and transparency by expecting investigators to consider SABV, NIH will not require any specific research design or method for accomplishing this goal. Rather, the existing state of knowledge in a particular scientific area and the specific research question under study will both affect how an investigator considers sex and other basic biological variables. On that note, it is important to point out that NIH policy changes to ensure the consideration of basic biological variables like sex do not imply the necessary doubling of research animals in every experiment, contrary to what some in the research community have assumed. It is true, however, that investigators aiming to differentiate sex effects—that is, to look explicitly for sex differences—may require larger numbers of animals, or equal numbers of animals of both sexes, for adequate power to detect statistically significant effects. Typically, these types of projects grow from preliminary data that provide hints of sex-based influences that generate a testable hypothesis in larger sample sizes.
In other words, “considering sex as a biological variable” is not the same as “sex differences research.”
We’d also like to remind you of the specific revised application instructions and review language related to rigor and reproducibility. Relevant biological variables such as sex will be assessed as part of the approach review criterion for research project grant applications, and as part of the research plan criterion for mentored career development award applications.
As previously noted by NIH leadership, consideration of relevant biological variables, such as sex, is crucial in the development of rigorous and reproducible experimental design. We hope you find helpful our posted guidance, ORWH additional guidance, and Dr. Clayton’s recent article, and we look forward to ongoing dialogue as we work to maximize the impact of our nation’s investment in biomedical research.