Medical research: Lack of sex and gender variables in many COVID-19 clinical studies

Only 4% of studies investigating therapeutic approaches for the treatment of COVID-19 registered on ClinicalTrials.gov explicitly reported a plan to include sex and/or gender as an analytical variable, according to a paper published in Nature Communications.

Sex and gender differences impact the incidence of SARS-CoV-2 infection and COVID-19 mortality. The inclusion of sex as a variable could aid in the identification of effective interventions and provide insights into COVID-19 pathology. Gender (a socially constructed variable that can describe identity, norms and relations between individuals) can affect access to testing, diagnosis, medical care and treatments and also influences the availability of social, economic and logistical support. Excluding sex differences in reporting results of clinical trials could lead to an increase in the risk of side effects for the excluded sex, while not addressing gender as a variable misses an opportunity to address healthcare inequality.

Sabine Oertelt-Prigione and colleagues analysed the inclusion of sex and gender in COVID-19 studies registered on ClinicalTrials.gov (a US clinical trial registration site) between 01 January 2020 and 26 January 2021. The authors identified 237 studies that planned sex-matched or representative samples or emphasised sex and/or gender reporting, and 178 studies that reported a plan to include sex and/or gender as an analytical variable. However, out of the 4,420 studies registered, the majority (2,496 studies) did not refer to sex or gender in the registration of the trial, and 935 studies mentioned sex or gender solely in the context of recruitment. Furthermore, out of the 45 randomised control trial publications for pharmacological interventions for COVID-19, only 8 reported disaggregated results by sex or subgroup analyses.

The authors caveat that their findings only examine ClinicalTrials.gov, which may affect the global applicability of their findings. They also state that sample sizes and disciplinary cultures may affect the inclusion of sex or gender within studies and that researchers may not have provided full information about sex and/or gender analyses when they registered their studies. However, they argue all researchers working in COVID-19 and SARS-CoV-2 research should implement a sex-specific methodology and more comprehensive analysis should address gender-related impacts and identify specific subgroup experiences and barriers to access.