Sex and gender considerations in randomized controlled trials in critical care nephrology: a meta-epidemiologic study

Abstract

Background: How sex and gender are considered in randomized controlled trials (RCTs) in critical care nephrology is unclear. We aimed to perform a meta-epidemiologic study to describe the representation, sex and gender reporting, and sex- and gender-based analyses (SGBA) in high-impact RCTs in critical care nephrology. Methods: We searched the Web of Science Core Collection for critical care nephrology papers from 2000 to 2024. We included trials published in high-impact journals in general medicine, pediatrics, critical care, and nephrology. The main outcome was the proportion of female/woman participants enrolled and the association with trial characteristics, findings, and women authorship. We estimated the participation-to-prevalence ratio (PPR) to evaluate the representativeness of females within identified RCTs and selected case-mix and disease populations. Sex and gender reporting and SGBA were investigated. Results: A total of 117 RCTs, including 106,057 participants, were included. Sex (54.7%), gender (26.5%), both (2.6%), or none (16.2%) terminology were used for reporting. Male/female (82.1%), men/women (11.1%), both (4.3%), boys/girls (0.9%) and none (1.7%) were used as descriptors. Of the 115 RCTs with available sex/gender data, the median proportion of female/women participants was 35.4% (interquartile range (IQR) 31.2%-40.8%). Pediatric age group and process of care as an intervention were independently associated with the proportion of female/women participants. The median PPR was 0.89 (IQR 0.8-1.06), except in major surgery, for which PPR was 0.67 (IQR 0.29-0.73). Twelve (10.9%) and 49 (41.9%) studies used sex and/or gender as inclusion and exclusion criteria, respectively; 5 (4.3%) studies used sex/gender-stratified randomization; and 35 (29.9%) studies performed SGBA. RCTs with pregnancy, lactation, or women of childbearing age as exclusion criteria had a lower enrollment of female/women participants than RCTs that did not (33.6% vs. 36.8%, P = 0.04). Exclusion criteria of pregnancy, lactation, or childbearing age were considered strongly justified, potentially justified, and poorly justified in 36.1%, 14.9%, and 48.9%, respectively. There were no changes in the representation of females/women and SGBA across identified RCTs over the search range. Conclusions: Females/women are less frequently represented in critical care nephrology RCTs. Significant gaps exist in sex- and gender-specific eligibility criteria, reporting, and analysis.