Recommendations for incorporating sex and gender in research
EDI Update
The following summary was prepared by Dr. Lisa Isaac, Director of Equity, Diversity and Inclusion, Department of Anesthesiology and Pain Medicine, University of Toronto.
Dear colleagues,
I am excited to share a new article, published in Nature Neuroscience, that outlines recommendations for incorporating and studying sex and gender as variables in research. The article highlights the importance of considering sex and gender in research to improve reproducibility, reduce variability, and enhance the translatability of findings. The recommendations were developed by the international PAINDIFF Network, comprising 32 experts, of whom three are from the University of Toronto, one of whom worked with the Hospital for Sick Children chronic pain clinic (Dr. Jennifer Stinson, NP PhD), and from 22 institutions across eight countries, supported by ERA-NET NEURON. Although focused on pain research, The PAINDIFF Network provided broad recommendations on methodological approaches for best practices in studying and reporting sex and gender (as variables in pain research), separated into Universal, Preclinical and Human/Research Recommendations (but are applicable to research more broadly).
Key Recommendations:
Universal Recommendations (Applicable to both preclinical and human/clinical studies, and therefore focusing on sex, rather than gender):
Include both males and females as standard practice unless a valid reason exists not to do so.
Account for sex in randomization, counterbalancing, and testing order.
Use adequately powered study designs to detect sex differences when they are the primary experimental variable.
Provide detailed reporting of experimental design, including the sex of the experimenter when possible.
Conduct sex-disaggregated analysis and reporting, and make raw data publicly available.
Preclinical Research Recommendations:
Report the sex of cell lines, primary cells, and tissues used in research.
Testing for estrous cycle stage is not always necessary; decisions should be informed by existing evidence.
Include detailed reporting of housing, environmental conditions, and experimental design.
Human/Clinical Research Recommendations:
Ask participants about their sex assigned at birth and self-identified gender.
Include a "prefer/choose not to say" option for sex and gender questions.
Provide an open-text box for gender identity to capture nuances.
Report the number of individuals with diverse gender identities and make raw data accessible for further study while ensuring anonymity.
Collect and report sex-specific variables, such as hormonal status, to better inform analyses.
Methodology:
The recommendations were developed through:
A literature review of existing guidelines and practices.
An international cross-sectional survey of 483 pain researchers.
Multidisciplinary network meetings and consensus discussions.
Outcomes:
The survey revealed that while most researchers consider sex as a variable, many do not routinely include both sexes or analyze sex differences. Gender is even less frequently considered in human/clinical research. Barriers include lack of resources, time, and expertise, as well as perceived irrelevance to research questions.
Stakeholder Recommendations:
The document emphasizes the need for researchers, journal editors, reviewers, funding agencies, policymakers, and healthcare providers to adopt and support sex and gender considerations in research. This includes allocating resources, ensuring diverse representation, and delivering research-informed care.
Conclusion:
The recommendations aim to standardize methodological approaches for studying sex and gender in pain research, reduce variability, and facilitate reproducibility across research settings. While developed for pain research, the guidelines are broadly applicable across biopsychosocial sciences. Widespread adoption is expected to lead to better and more equitable treatment outcomes.
