Lack of consideration of sex and gender in COVID-19 clinical studies

Abstract

Sex and gender differences impact the incidence of SARS-CoV-2 infection and COVID-19 mortality. Furthermore, sex differences influence the frequency and severity of pharmacological side effects. A large number of clinical trials to develop new therapeutic approaches and vaccines for COVID-19 are ongoing. We investigated the inclusion of sex and/or gender in COVID-19 studies on ClinicalTrials.gov, collecting data for the period January 1, 2020 to January 26, 2021. Here, we show that of the 4,420 registered SARS-CoV-2/COVID-19 studies, 935 (21.2%) address sex/gender solely in the context of recruitment, 237 (5.4%) plan sex-matched or representative samples or emphasized sex/gender reporting, and only 178 (4%) explicitly report a plan to include sex/gender as an analytical variable. Just eight (17.8%) of the 45 COVID-19 related clinical trials published in scientific journals until December 15, 2020 report sex-disaggregated results or subgroup analyses.

Long COVID risk - a signal to address sex hormones and women's health

“…Failure to explore sex-specific risk and outcomes in COVID-19 is unethical [10] and associated with several risks. Firstly, it threatens opportunities for identifying mechanisms and treatment targets, where at present, no treatments exist.…”

“…Looking ahead, there is urgent need for robust research to help understand the epidemiological basis, as well as the underlying biological mechanisms for sex-differences in Long COVID. The deficit in sex and gender-specific outcomes within clinical trials is recognised, with calls for the systematic application of sex-specific methodologies [10] . Sex-disaggregated data underpins this vital research, along with power calculations which consider sex as an analytical variable a priori [10] .…”

“…The deficit in sex and gender-specific outcomes within clinical trials is recognised, with calls for the systematic application of sex-specific methodologies [10] . Sex-disaggregated data underpins this vital research, along with power calculations which consider sex as an analytical variable a priori [10] .…”

Sex-related susceptibility in coronavirus disease 2019 (COVID-19): Proposed mechanisms

“…According to the study of Brady et al, only 4% of registered COVID-19 studies considered sex/gender as an analytical variable, while few (21.2%) mentioned sex/gender solely as a recruitment criterion ( Brady et al, 2021 ). Ignoring sex biases in drug efficacy and reactivity may cause increased adverse reactions or even deaths ( Bischof et al, 2020b ).…”

Just a Reflection: Does Drug Repurposing Perpetuate Sex-Gender Bias in the Safety Profile?

“…This situation leads to poor scientific rigor, and it makes it difficult to compare the efficacy of different therapies [ 17 , 20 ]. Currently, only very few registered clinical trials for COVID-19 in ClinicalTrials.gov present sex and gender as explicit criteria of enrollment or analytical variables [ 77 ]. In particular, women are under-enrolled, the outcomes are scarcely disaggregated by sex, and sex and gender differences are inadequately considered in the analysis of the data [ 78 ].…”