Why “sex as a biological variable” conflicts with precision medicine initiatives
Marina DiMarco, Helen Hailin Zhao, Marion Boulicault, Sarah S. Richardson
Abstract
Policies that require male-female sex comparisons in all areas of biomedical research conflict with the goal of improving health outcomes through context-sensitive individualization of medical care. Sex, like race, requires a rigorous, contextual approach in precision medicine. A “sex contextualist” approach to gender-inclusive medicine better aligns with this aim. Policies that require male-female sex comparisons in all areas of biomedical research conflict with the goal of improving health outcomes through context-sensitive individualization of medical care. Sex, like race, requires a rigorous, contextual approach in precision medicine. A “sex contextualist” approach to gender-inclusive medicine better aligns with this aim. Main textIn recent years, biologists and women’s health advocates in the field of “sex-based biology” have aligned their work with the goals of precision medicine.1Clayton J. Minority Health: A Milestone on the Road to Precision Medicine. Office of Research on Women’s Health. April 25, 2016.2016https://orwh.od.nih.gov/about/director/messages/milestone-precision-medicineGoogle Scholar Attending to sex, they argue, is part and parcel of both an individualized approach to patient care and a precise approach to gender-specific medicine. This is most clear in the literature supporting the NIH’s Sex as a Biological Variable (SABV) policy requiring the inclusion of male and female materials in preclinical research. Dr. Janine Clayton of the NIH Office of Research on Women’s Health (ORWH), a leading advocate of the much-debated mandate, has characterized the policy as “one step toward the more individualized approach to human health that is the trajectory of medical practice and the aim of the Precision Medicine Initiative.”1Clayton J. Minority Health: A Milestone on the Road to Precision Medicine. Office of Research on Women’s Health. April 25, 2016.2016https://orwh.od.nih.gov/about/director/messages/milestone-precision-medicineGoogle ScholarPrecision medicine advocates aim to account for individual variability using large multidimensional genomic, environmental, and lifestyle datasets.2Geneviève L.D. Martani A. Shaw D. Elger B.S. Wangmo T. Structural Racism in Precision Medicine: Leaving No One Behind.BMC Med. Ethics. 2020; 21: 17https://doi.org/10.1186/s12910-020-0457-8Crossref PubMed Scopus (26) Google Scholar Policies that require male-female sex comparisons in all areas of biomedical research are in tension with the goal of improving health outcomes through context-sensitive individualization of medical care. As critics of SABV mandates, including ourselves, have argued, an intensive focus on documenting sex differences risks producing decontextualized results with little relevance to human health.3Richardson S.S. Reiches M. Shattuck-Heidorn H. LaBonte M.L. Consoli T. Opinion: Focus on Preclinical Sex Differences Will Not Address Women’s and Men’s Health Disparities.Proc. Natl. Acad. Sci. USA. 2015; 112: 13419-13420https://doi.org/10.1073/pnas.1516958112Crossref PubMed Scopus (50) Google Scholar For example, early claims that excess male COVID-19 mortality was due to biological sex differences obscured within-sex differences in mortality, such as the fact that Black women died at higher rates than white women and white men, and neglected important social candidate causes, such as patterns of occupational exposure, compliance with masking and hand-washing advice, and access to healthcare.4Rushovich T. Boulicault M. Chen J.T. Danielsen A.C. Tarrant A. Richardson S.S. Shattuck-Heidorn H. Sex Disparities in COVID-19 Mortality Vary Across US Racial Groups.J. Gen. Intern. Med. 2021; 36: 1696-1701https://doi.org/10.1007/s11606-021-06699-4Crossref PubMed Scopus (31) Google ScholarA one-size-fits-all approach to sex also comes at the expense of the rigor and precision at which precision medicine aims. In a recent reanalysis of 147 articles identified by Nicole C. Woitowich and colleagues5Woitowich N.C. Beery A. Woodruff T. A 10-Year Follow-up Study of Sex Inclusion in the Biological Sciences.ELife. 2020; 9: e56344https://doi.org/10.7554/eLife.56344Crossref PubMed Scopus (80) Google Scholar as conforming to best practices for sex-based biology, Yesenia Garcia-Sifuentes and Donna L. Maney6Garcia-Sifuentes Y. Maney D.L. Reporting and Misreporting of Sex Differences in the Biological Sciences.ELife. 2021; 10: e70817https://doi.org/10.7554/eLife.70817Crossref PubMed Scopus (28) Google Scholar showed that over 70% of papers claiming to find differences in treatment responses between males and females did not perform the statistical comparisons that would be necessary to demonstrate that a sex difference existed. Similarly, a reanalysis of a headline-making paper purporting to show sex differences in immune response to COVID-19 demonstrated that the evidence overwhelmingly pointed to null findings of sex similarity.7Shattuck-Heidorn H. Danielsen A.C. Gompers A. Bruch J.D. Zhao H. Boulicault M. et al.A Finding of Sex Similarities Rather Than Differences in COVID-19 Outcomes.Nature. 2021; 597: E7-E9https://doi.org/10.1038/s41586-021-03644-7Crossref PubMed Scopus (7) Google Scholar Furthermore, researchers who study sex differences rarely specify how they operationalize sex. All too commonly, researchers assert sex differences based on aggregations of data by physician- or patient-reported “sex” or “gender” without specification and actual analysis of underlying variables that account for these differences, and an a priori study design suitable to doing so. These results replicate long-standing concerns that methodological shortcomings render sex comparisons in biomedical research spurious at worst and unintelligible at best,8Patsopoulos N.A. Tatsioni A. Ioannidis J.P.A. Claims of Sex Differences: an Empirical Assessment in Genetic Associations.JAMA. 2007; 298: 880-893https://doi.org/10.1001/jama.298.8.880Crossref PubMed Scopus (115) Google Scholar resulting in a “catalogue of differences”9Springer K.W. Mager Stellman J. Jordan-Young R.M. Beyond a Catalogue of Differences: a Theoretical Frame and Good Practice Guidelines for Researching Sex/Gender in Human Health.Soc. Sci. Med. 2012; 74: 1817-1824https://doi.org/10.1016/j.socscimed.2011.05.033Crossref PubMed Scopus (186) Google Scholar with little relation to real-life, embodied health disparities. As epidemiologist Janet Rich-Edwards and colleagues warn, “without careful methodology, the pursuit of sex difference research, despite a mandate from funding agencies, will result in a literature of contradiction.”10Rich-Edwards J.W. Kaiser U.B. Chen G.L. Manson J.E. Goldstein J.M. Sex and Gender Differences Research Design for Basic, Clinical, and Population Studies: Essentials for Investigators.Endocr. Rev. 2018; 39: 424-439Crossref PubMed Scopus (77) Google ScholarPrecision medicine visionaries understand these issues well when it comes to race. For example, in a recent high-profile perspective in Cell, Joshua Denny, director of the NIH’s “All of Us” initiative, and NIH Director Francis Collins sketched an expansive vision for the future of “Precision Medicine in 2030.”11Denny J.C. Collins F.S. Precision Medicine in 2030 - Seven Ways to Transform Healthcare.Cell. 2021; 184: 1415-1419https://doi.org/10.1016/j.cell.2021.01.015Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Race, they argued, is just the sort of crude category that precision medicine is poised to As they the of as a a of and biological and A precision medicine by would in the of social of health in both research and care in with more precise of and and and and Collins precision medicine with the aim of the of crude biological such as in biomedical research and in the In doing they a of and who have that race, as a biological is at best a and at worst a of social M. D. of Human PubMed Scopus Google are better to the analysis of variables in biomedical research, that well with the of precision medicine. For example, in to to and data by male and female sex, a “sex contextualist” the and of sex as a biomedical research S.S. Sex and Practice in 2021; Google Scholar this in practice is and biological variables including individual social and and or and of biological This biologists well that with biological of biological from to and of “sex” not in or In such as sex be well as a in such as it Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar Furthermore, such as over the of an and are as for by and social Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar Sex that male-female in are or to and that findings of sex differences in not be to this variables are not as or not the of a research or to the of research and that researchers by for sex in and preclinical research, and for of biological and social variables in of health and This that and with the and the of these this with the relevance of of sex to be an than an a priori race, variables be to for and for As L. and Shattuck-Heidorn are and when of sex are on to in this the are as for and biological differences are to be as to by Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar A approach the of the between biological variables and which researchers in pursuit of and treatment the social of sex-based such as the of that from also that the of sex in more than advocates Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar As to by funding mandates, a approach researchers both the and the of sex-based in that better the and social of and which research medicine such as the “All of Us” will research and funding for to as of sex and the of precision medicine on the rigor and with which of precision are to crude such as male and female sex. of concerns and L.D. Martani A. Shaw D. Elger B.S. Wangmo T. Structural Racism in Precision Medicine: Leaving No One Behind.BMC Med. Ethics. 2020; 21: 17https://doi.org/10.1186/s12910-020-0457-8Crossref PubMed Scopus (26) Google Precision Medicine Scholar a precision approach to biomedical research a of sex and from and “sex” and toward of biological with the study of social and that to of sex precision medicine as SABV in the of decontextualized and claims of differences as or sex as a biological from research social and from and is Main textIn recent years, biologists and women’s health advocates in the field of “sex-based biology” have aligned their work with the goals of precision medicine.1Clayton J. Minority Health: A Milestone on the Road to Precision Medicine. Office of Research on Women’s Health. April 25, 2016.2016https://orwh.od.nih.gov/about/director/messages/milestone-precision-medicineGoogle Scholar Attending to sex, they argue, is part and parcel of both an individualized approach to patient care and a precise approach to gender-specific medicine. This is most clear in the literature supporting the NIH’s Sex as a Biological Variable (SABV) policy requiring the inclusion of male and female materials in preclinical research. Dr. Janine Clayton of the NIH Office of Research on Women’s Health (ORWH), a leading advocate of the much-debated mandate, has characterized the policy as “one step toward the more individualized approach to human health that is the trajectory of medical practice and the aim of the Precision Medicine Initiative.”1Clayton J. Minority Health: A Milestone on the Road to Precision Medicine. Office of Research on Women’s Health. April 25, 2016.2016https://orwh.od.nih.gov/about/director/messages/milestone-precision-medicineGoogle ScholarPrecision medicine advocates aim to account for individual variability using large multidimensional genomic, environmental, and lifestyle datasets.2Geneviève L.D. Martani A. Shaw D. Elger B.S. Wangmo T. Structural Racism in Precision Medicine: Leaving No One Behind.BMC Med. Ethics. 2020; 21: 17https://doi.org/10.1186/s12910-020-0457-8Crossref PubMed Scopus (26) Google Scholar Policies that require male-female sex comparisons in all areas of biomedical research are in tension with the goal of improving health outcomes through context-sensitive individualization of medical care. As critics of SABV mandates, including ourselves, have argued, an intensive focus on documenting sex differences risks producing decontextualized results with little relevance to human health.3Richardson S.S. Reiches M. Shattuck-Heidorn H. LaBonte M.L. Consoli T. Opinion: Focus on Preclinical Sex Differences Will Not Address Women’s and Men’s Health Disparities.Proc. Natl. Acad. Sci. USA. 2015; 112: 13419-13420https://doi.org/10.1073/pnas.1516958112Crossref PubMed Scopus (50) Google Scholar For example, early claims that excess male COVID-19 mortality was due to biological sex differences obscured within-sex differences in mortality, such as the fact that Black women died at higher rates than white women and white men, and neglected important social candidate causes, such as patterns of occupational exposure, compliance with masking and hand-washing advice, and access to healthcare.4Rushovich T. Boulicault M. Chen J.T. Danielsen A.C. Tarrant A. Richardson S.S. Shattuck-Heidorn H. Sex Disparities in COVID-19 Mortality Vary Across US Racial Groups.J. Gen. Intern. Med. 2021; 36: 1696-1701https://doi.org/10.1007/s11606-021-06699-4Crossref PubMed Scopus (31) Google ScholarA one-size-fits-all approach to sex also comes at the expense of the rigor and precision at which precision medicine aims. In a recent reanalysis of 147 articles identified by Nicole C. Woitowich and colleagues5Woitowich N.C. Beery A. Woodruff T. A 10-Year Follow-up Study of Sex Inclusion in the Biological Sciences.ELife. 2020; 9: e56344https://doi.org/10.7554/eLife.56344Crossref PubMed Scopus (80) Google Scholar as conforming to best practices for sex-based biology, Yesenia Garcia-Sifuentes and Donna L. Maney6Garcia-Sifuentes Y. Maney D.L. Reporting and Misreporting of Sex Differences in the Biological Sciences.ELife. 2021; 10: e70817https://doi.org/10.7554/eLife.70817Crossref PubMed Scopus (28) Google Scholar showed that over 70% of papers claiming to find differences in treatment responses between males and females did not perform the statistical comparisons that would be necessary to demonstrate that a sex difference existed. Similarly, a reanalysis of a headline-making paper purporting to show sex differences in immune response to COVID-19 demonstrated that the evidence overwhelmingly pointed to null findings of sex similarity.7Shattuck-Heidorn H. Danielsen A.C. Gompers A. Bruch J.D. Zhao H. Boulicault M. et al.A Finding of Sex Similarities Rather Than Differences in COVID-19 Outcomes.Nature. 2021; 597: E7-E9https://doi.org/10.1038/s41586-021-03644-7Crossref PubMed Scopus (7) Google Scholar Furthermore, researchers who study sex differences rarely specify how they operationalize sex. All too commonly, researchers assert sex differences based on aggregations of data by physician- or patient-reported “sex” or “gender” without specification and actual analysis of underlying variables that account for these differences, and an a priori study design suitable to doing so. These results replicate long-standing concerns that methodological shortcomings render sex comparisons in biomedical research spurious at worst and unintelligible at best,8Patsopoulos N.A. Tatsioni A. Ioannidis J.P.A. Claims of Sex Differences: an Empirical Assessment in Genetic Associations.JAMA. 2007; 298: 880-893https://doi.org/10.1001/jama.298.8.880Crossref PubMed Scopus (115) Google Scholar resulting in a “catalogue of differences”9Springer K.W. Mager Stellman J. Jordan-Young R.M. Beyond a Catalogue of Differences: a Theoretical Frame and Good Practice Guidelines for Researching Sex/Gender in Human Health.Soc. Sci. Med. 2012; 74: 1817-1824https://doi.org/10.1016/j.socscimed.2011.05.033Crossref PubMed Scopus (186) Google Scholar with little relation to real-life, embodied health disparities. As epidemiologist Janet Rich-Edwards and colleagues warn, “without careful methodology, the pursuit of sex difference research, despite a mandate from funding agencies, will result in a literature of contradiction.”10Rich-Edwards J.W. Kaiser U.B. Chen G.L. Manson J.E. Goldstein J.M. Sex and Gender Differences Research Design for Basic, Clinical, and Population Studies: Essentials for Investigators.Endocr. Rev. 2018; 39: 424-439Crossref PubMed Scopus (77) Google ScholarPrecision medicine visionaries understand these issues well when it comes to race. For example, in a recent high-profile perspective in Cell, Joshua Denny, director of the NIH’s “All of Us” initiative, and NIH Director Francis Collins sketched an expansive vision for the future of “Precision Medicine in 2030.”11Denny J.C. Collins F.S. Precision Medicine in 2030 - Seven Ways to Transform Healthcare.Cell. 2021; 184: 1415-1419https://doi.org/10.1016/j.cell.2021.01.015Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Race, they argued, is just the sort of crude category that precision medicine is poised to As they the of as a a of and biological and A precision medicine by would in the of social of health in both research and care in with more precise of and and and and Collins precision medicine with the aim of the of crude biological such as in biomedical research and in the In doing they a of and who have that race, as a biological is at best a and at worst a of social M. D. of Human PubMed Scopus Google are better to the analysis of variables in biomedical research, that well with the of precision medicine. For example, in to to and data by male and female sex, a “sex contextualist” the and of sex as a biomedical research S.S. Sex and Practice in 2021; Google Scholar this in practice is and biological variables including individual social and and or and of biological This biologists well that with biological of biological from to and of “sex” not in or In such as sex be well as a in such as it Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar Furthermore, such as over the of an and are as for by and social Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar Sex that male-female in are or to and that findings of sex differences in not be to this variables are not as or not the of a research or to the of research and that researchers by for sex in and preclinical research, and for of biological and social variables in of health and This that and with the and the of these this with the relevance of of sex to be an than an a priori race, variables be to for and for As L. and Shattuck-Heidorn are and when of sex are on to in this the are as for and biological differences are to be as to by Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar A approach the of the between biological variables and which researchers in pursuit of and treatment the social of sex-based such as the of that from also that the of sex in more than advocates Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar As to by funding mandates, a approach researchers both the and the of sex-based in that better the and social of and which research medicine such as the “All of Us” will research and funding for to as of sex and the of precision medicine on the rigor and with which of precision are to crude such as male and female sex. of concerns and L.D. Martani A. Shaw D. Elger B.S. Wangmo T. Structural Racism in Precision Medicine: Leaving No One Behind.BMC Med. Ethics. 2020; 21: 17https://doi.org/10.1186/s12910-020-0457-8Crossref PubMed Scopus (26) Google Precision Medicine Scholar a precision approach to biomedical research a of sex and from and “sex” and toward of biological with the study of social and that to of sex precision medicine as SABV in the of decontextualized and claims of differences as or sex as a biological from research social and from and is In recent years, biologists and women’s health advocates in the field of “sex-based biology” have aligned their work with the goals of precision medicine.1Clayton J. Minority Health: A Milestone on the Road to Precision Medicine. Office of Research on Women’s Health. April 25, 2016.2016https://orwh.od.nih.gov/about/director/messages/milestone-precision-medicineGoogle Scholar Attending to sex, they argue, is part and parcel of both an individualized approach to patient care and a precise approach to gender-specific medicine. This is most clear in the literature supporting the NIH’s Sex as a Biological Variable (SABV) policy requiring the inclusion of male and female materials in preclinical research. Dr. Janine Clayton of the NIH Office of Research on Women’s Health (ORWH), a leading advocate of the much-debated mandate, has characterized the policy as “one step toward the more individualized approach to human health that is the trajectory of medical practice and the aim of the Precision Medicine Initiative.”1Clayton J. Minority Health: A Milestone on the Road to Precision Medicine. Office of Research on Women’s Health. April 25, 2016.2016https://orwh.od.nih.gov/about/director/messages/milestone-precision-medicineGoogle Scholar Precision medicine advocates aim to account for individual variability using large multidimensional genomic, environmental, and lifestyle datasets.2Geneviève L.D. Martani A. Shaw D. Elger B.S. Wangmo T. Structural Racism in Precision Medicine: Leaving No One Behind.BMC Med. Ethics. 2020; 21: 17https://doi.org/10.1186/s12910-020-0457-8Crossref PubMed Scopus (26) Google Scholar Policies that require male-female sex comparisons in all areas of biomedical research are in tension with the goal of improving health outcomes through context-sensitive individualization of medical care. As critics of SABV mandates, including ourselves, have argued, an intensive focus on documenting sex differences risks producing decontextualized results with little relevance to human health.3Richardson S.S. Reiches M. Shattuck-Heidorn H. LaBonte M.L. Consoli T. Opinion: Focus on Preclinical Sex Differences Will Not Address Women’s and Men’s Health Disparities.Proc. Natl. Acad. Sci. USA. 2015; 112: 13419-13420https://doi.org/10.1073/pnas.1516958112Crossref PubMed Scopus (50) Google Scholar For example, early claims that excess male COVID-19 mortality was due to biological sex differences obscured within-sex differences in mortality, such as the fact that Black women died at higher rates than white women and white men, and neglected important social candidate causes, such as patterns of occupational exposure, compliance with masking and hand-washing advice, and access to healthcare.4Rushovich T. Boulicault M. Chen J.T. Danielsen A.C. Tarrant A. Richardson S.S. Shattuck-Heidorn H. Sex Disparities in COVID-19 Mortality Vary Across US Racial Groups.J. Gen. Intern. Med. 2021; 36: 1696-1701https://doi.org/10.1007/s11606-021-06699-4Crossref PubMed Scopus (31) Google Scholar A one-size-fits-all approach to sex also comes at the expense of the rigor and precision at which precision medicine aims. In a recent reanalysis of 147 articles identified by Nicole C. Woitowich and colleagues5Woitowich N.C. Beery A. Woodruff T. A 10-Year Follow-up Study of Sex Inclusion in the Biological Sciences.ELife. 2020; 9: e56344https://doi.org/10.7554/eLife.56344Crossref PubMed Scopus (80) Google Scholar as conforming to best practices for sex-based biology, Yesenia Garcia-Sifuentes and Donna L. Maney6Garcia-Sifuentes Y. Maney D.L. Reporting and Misreporting of Sex Differences in the Biological Sciences.ELife. 2021; 10: e70817https://doi.org/10.7554/eLife.70817Crossref PubMed Scopus (28) Google Scholar showed that over 70% of papers claiming to find differences in treatment responses between males and females did not perform the statistical comparisons that would be necessary to demonstrate that a sex difference existed. Similarly, a reanalysis of a headline-making paper purporting to show sex differences in immune response to COVID-19 demonstrated that the evidence overwhelmingly pointed to null findings of sex similarity.7Shattuck-Heidorn H. Danielsen A.C. Gompers A. Bruch J.D. Zhao H. Boulicault M. et al.A Finding of Sex Similarities Rather Than Differences in COVID-19 Outcomes.Nature. 2021; 597: E7-E9https://doi.org/10.1038/s41586-021-03644-7Crossref PubMed Scopus (7) Google Scholar Furthermore, researchers who study sex differences rarely specify how they operationalize sex. All too commonly, researchers assert sex differences based on aggregations of data by physician- or patient-reported “sex” or “gender” without specification and actual analysis of underlying variables that account for these differences, and an a priori study design suitable to doing so. These results replicate long-standing concerns that methodological shortcomings render sex comparisons in biomedical research spurious at worst and unintelligible at best,8Patsopoulos N.A. Tatsioni A. Ioannidis J.P.A. Claims of Sex Differences: an Empirical Assessment in Genetic Associations.JAMA. 2007; 298: 880-893https://doi.org/10.1001/jama.298.8.880Crossref PubMed Scopus (115) Google Scholar resulting in a “catalogue of differences”9Springer K.W. Mager Stellman J. Jordan-Young R.M. Beyond a Catalogue of Differences: a Theoretical Frame and Good Practice Guidelines for Researching Sex/Gender in Human Health.Soc. Sci. Med. 2012; 74: 1817-1824https://doi.org/10.1016/j.socscimed.2011.05.033Crossref PubMed Scopus (186) Google Scholar with little relation to real-life, embodied health disparities. As epidemiologist Janet Rich-Edwards and colleagues warn, “without careful methodology, the pursuit of sex difference research, despite a mandate from funding agencies, will result in a literature of contradiction.”10Rich-Edwards J.W. Kaiser U.B. Chen G.L. Manson J.E. Goldstein J.M. Sex and Gender Differences Research Design for Basic, Clinical, and Population Studies: Essentials for Investigators.Endocr. Rev. 2018; 39: 424-439Crossref PubMed Scopus (77) Google Scholar Precision medicine visionaries understand these issues well when it comes to race. For example, in a recent high-profile perspective in Cell, Joshua Denny, director of the NIH’s “All of Us” initiative, and NIH Director Francis Collins sketched an expansive vision for the future of “Precision Medicine in 2030.”11Denny J.C. Collins F.S. Precision Medicine in 2030 - Seven Ways to Transform Healthcare.Cell. 2021; 184: 1415-1419https://doi.org/10.1016/j.cell.2021.01.015Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar Race, they argued, is just the sort of crude category that precision medicine is poised to As they the of as a a of and biological and A precision medicine by would in the of social of health in both research and care in with more precise of and and and and Collins precision medicine with the aim of the of crude biological such as in biomedical research and in the In doing they a of and who have that race, as a biological is at best a and at worst a of social M. D. of Human PubMed Scopus Google Scholar Similarly, are better to the analysis of variables in biomedical research, that well with the of precision medicine. For example, in to to and data by male and female sex, a “sex contextualist” the and of sex as a biomedical research S.S. Sex and Practice in 2021; Google Scholar this in practice is and biological variables including individual social and and or and of biological This biologists well that with biological of biological from to and These of “sex” not in or In such as sex be well as a in such as it Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar Furthermore, such as over the of an and are as for by and social Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar Sex that male-female in are or to and that findings of sex differences in not be to this variables are not as or not the of a research or aim. to the of research and that researchers by for sex in and preclinical research, and for of biological and social variables in of health and This that and with the and the of these this with the relevance of of sex to be an than an a priori race, variables be to for and for As L. and Shattuck-Heidorn are and when of sex are on to in this the are as for and biological differences are to be as to by Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar A approach the of the between biological variables and which researchers in pursuit of and treatment the social of sex-based such as the of that from also that the of sex in more than advocates Shattuck-Heidorn H. the and the of J. 2021; PubMed Scopus Google Scholar As to by funding mandates, a approach researchers both the and the of sex-based in that better the and social of and which research Precision medicine such as the “All of Us” will research and funding for to as of sex and the of precision medicine on the rigor and with which of precision are to crude such as male and female sex. of concerns and L.D. Martani A. Shaw D. Elger B.S. Wangmo T. Structural Racism in Precision Medicine: Leaving No One Behind.BMC Med. Ethics. 2020; 21: 17https://doi.org/10.1186/s12910-020-0457-8Crossref PubMed Scopus (26) Google Precision Medicine Scholar a precision approach to biomedical research a of sex and from and “sex” and toward of biological with the study of social and that to of sex precision medicine as SABV in the of decontextualized and claims of differences as or sex as a biological from research social and from and is to the at and for that to the of this and and and and and