Inclusion of sex and gender in biomedical research: survey of clinical research proposed at the University of Pennsylvania

Abstract

BackgroundThe 2015 National Institutes of Health (NIH) policy that sex be considered as a biological variable (SABV) is now a critical part of the peer-review process for NIH funding as well as publication in several high-impact scientific journals. We sought to determine the degree to which biomedical researchers at the University of Pennsylvania already consider SABV or gender in their research.MethodsWe reviewed 240 research protocols approved by the University of Pennsylvania Investigational Review Board (IRB) consecutively submitted between January and July 2016. Each protocol was searched for the terms sex, gender, male, female, man, and woman and justifications related to the population under study. A PubMed search was conducted to determine the current state of knowledge regarding potential sex and/or gender differences with respect to protocol topic. Data were summarized using descriptive statistics.ResultsOf the 165 (68.8%) protocols that included one of the search terms, only 24 (14.5%) provided justification for the choice of the sex/gender of the population studied. Sixty-three percent (n = 151) of the protocols focused on topics for which the extant literature supports at least a moderate degree of sex/gender differences in some aspect of the disorder/condition being studied. Of these, only three (2.0%) indicated that the investigator would consider sex or gender impact on their primary outcomes.ConclusionsReview of a subset of IRB protocols submitted at a major research institution suggests that very few investigators are considering sex or gender as important variables in their clinical research at the stage of protocol development. IRBs are in an excellent position to encourage investigators to consider SABV and gender in order to enhance the rigor of research design, maximize the importance of the resulting knowledge, and ensure that subject selection is equitable. These findings serve as the basis for developing an intervention at the level of IRB protocol development and submission that will promote consideration of SABV and/or gender, factors with critical import to patient safety and efficacy of interventions.

Inclusion of Sex and Gender in Emergency Medicine Research—A 2018 Update

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Sex-related differences in markers of immune activation in virologically suppressed HIV-infected patients

“…In 2015, the National Institutes of Health (NIH) established that sex is a biological variable (SABV) to take into account for NIH funding and scientific publication [1]. This statement was based on scientific evidence that sex affects innate and adaptive immunity and results in sex-specific outcomes of autoimmune pathologies, malignancies, infectious diseases, and vaccines [2].…”

Non-alcoholic Fatty Liver Disease as a Canonical Example of Metabolic Inflammatory-Based Liver Disease Showing a Sex-Specific Prevalence: Relevance of Estrogen Signaling

“…Despite the extensive, although probably underestimated, awareness on hepatic sex differences, the molecular mechanisms determining the sex-specific incidence of liver pathologies such as NAFLD are far to be unraveled. This knowledge has been prevented and affected by several limitations that stem from: (a) the paucity of available data on both sexes coming from pre- and clinical studies in which females are often underrepresented ( 12 , 417 ); (b) the inability to enroll females in clinical studies ( 418 – 420 ); (c) the limited and, in some cases, misleading conclusions reached by experimental designs that did not take into account the relative contribution of genetic and hormonal backgrounds and exclude the sexual hormones as potential confounding factors ( 12 , 417 ); (d) the lack of proper research tools helpful in investigating the genetic and/or hormonal factors relevant for the hepatic sexual dimorphism or the inability to use the available research tools in the best way ( 421 , 422 ); (e) the fragmentary and still incomplete view coming from several studies that often do not share common protocols or lack of significance for the low number of the samples analyzed ( 422 , 423 ); (f) the low, still insufficient commitment dedicated to dissemination of the results obtained from sex/gender research, such as educational programs addressed to health professionals (researchers, clinicians, scientific training programs, health institutions, etc.) and to society in general ( 419 , 423 – 425 ); g) the still limited policies aimed at promoting sex/gender research programs ( 426 – 428 ).…”