Updated instructions for the Approach section of the Research Strategy ask the applicant to:
Explain how relevant biological variables, such as sex, are factored into research designs and analyses for studies in vertebrate animals and humans. For example, strong justification from the scientific literature, preliminary data, or other relevant considerations, must be provided for applications proposing to study only one sex.
Several blog posts have been devoted to sex as biological variable so today we will focus on other biological variables you may need to consider.
As with sex, the clarifying instructions on consideration of relevant biological variables do not prescribe that the biological variable itself be studied. If biological variables are known to affect a system or disease model proposed forstudy, the application should discuss how you will control for these factors, if necessary.
So, what are some biological variables, other than sex, that might need to be considered when doing research in vertebrate animals? Let’s start with an example of early vaccine development in mice. It’s been well-established that C57BL/6 and Balb/c strains of mice produce different immune responses due to differing genetic backgrounds. Therefore, if an application proposes to study an immune response in mice, it may be necessary to indicate which strain will be used and why. Other variables that might be important include the vendor source or supplier, the age of the animals, since both can affect immune responses. Depending on the field and the research question, housing conditions may need to be considered, including the room temperature and light/dark cycles. Studies with mouse tissues or primary cells should also consider relevant biological variables, including sex, in proposing and reporting research.
Let’s next turn to biological variables in human studies. The NIH has already established that sex must be considered in proposing studies in humans. Other biological variables that may need to be considered include age, body mass index (BMI), socioeconomic status, or underlying health conditions. Many clinical studies already take these variables into account, but it is important that observations be reported. Variables such as sex, age, BMI, and underlying health conditions may also need to be considered when proposing and reporting studies with human biological samples, including blood and tissue. Consideration of other variables is critical to enable reviewers and the scientific community to assess the internal validity of a study – whether the findings hold up after accounting for confounding and selection biases – and the external validity of a study – whether the findings, even if internally valid, apply to the “real world.”
We believe that attention to relevant biological variables in your research design, analysis, and reporting will help enhance the reproducibility and translatability of biomedical research.
Coming up next: addressing authentication of key biological and/or chemical resources in your NIH grant applications.