Lack of consideration of sex and gender in clinical trials for COVID-19

Abstract

Sex and gender differences impact the incidence of SARS-CoV-2 infection and COVID-19 mortality. Furthermore, sex differences characterize the frequency and severity of pharmacological side effects. A large number of clinical trials are ongoing to develop new therapeutic approaches and vaccines for COVID-19. We investigated the inclusion of sex and/or gender in currently registered studies on ClinicalTrials.gov. Only 416 (16.7%) of the 2,484 registered SARS-CoV-2/COVID-19 trials mention sex/gender as recruitment criterion and only 103 (4.1%) allude to sex/gender in the description of the analysis phase. None of the 11 clinical trials published in scientific journals on June 2020 reported sex-disaggregated results. Hence, lack of consideration upon registration does not seem to be corrected during trial execution and reporting. Given the biological relevance and the potential risks of unwanted side effects, we urge researchers to focus on sex-disaggregated analyses already at the planning stage of COVID-19 trials.

Inadequate reporting of COVID-19 clinical studies: a renewed rationale for the Sex and Gender Equity in Research (SAGER) guidelines

“… 10 In a recent systematic review by Brady et al of COVID-19 registered studies, only 4.1% mention sex and/or gender in the analysis, with only ‘20 of the 1381 interventional trials planning to consider sex as a variable upon analysis’. 11 This analysis confirms the persistent lack of consideration for sex and gender at the planning stages of clinical trials on COVID-19 and in reporting. A recent report of the adverse effects following the administration of the Pfizer-BioNTech COVID-19 Vaccine in the USA reveals that more than 90% of anaphylaxis and non-anaphylaxis allergic reactions occurred in women, illustrating the importance of capturing these trends during clinical trials.…”

“…The gender blind reporting is particularly worrisome in the context of COVID-19, when scientific articles are being produced in an unprecedented volume and speed and risk generating biased and incomplete evidence that can hamper more tailored and effective response. 11 13–15 …”

Molecular and Biological Mechanisms Underlying Gender Differences in COVID-19 Severity and Mortality

“…There are currently several vaccines against SARS-CoV-2 that have been rolled out (158). Early reports of clinical trials for SARS-CoV-2 vaccination have not addressed sexual differences (159)(160)(161). Studies reported promising immunogenicity and safety outcomes.…”

Gender issues during the times of COVID‐19 pandemic

“…However, pregnant or breastfeeding women were eligible for the randomized controlled trial investigating the efficacy of dexamethasone on the 28-day mortality in patients who were hospitalized with COVID-19 [26] Both the Food and Drug Administration and European Medicines Agency have recommended the inclusion of sufficient numbers of subjects of both sexes in clinical trials, possibly at percentages adequate in representing the prevalence rates within the general population. In addition, the National Institutes of Health has adopted a code for the inclusion of both genders and ethnic minorities within clinical trials [27] A recent paper has investigated the inclusion of sex and/or gender data in currently registered COVID-19 studies on ClinicalTrials.gov [28] The authors found that only 416 (16.7%) of the 2484 registered SARS-CoV-2/COVID-19 trials mention sex/ gender as a recruitment criterion, and only 103 (4.1%) allude to sex/ gender in the description of the analysis phase. None of the 11 clinical trials published in scientific journals on June 2020 reported sexdisaggregated results.…”