Sex, Racial, and Ethnic Representation in COVID-19 Clinical Trials

Abstract

ImportanceSince the onset of the COVID-19 pandemic, there have been calls for COVID-19 clinical trials to be fully representative of all demographic groups. However, limited evidence is available about the sex, racial, and ethnic representation among COVID-19 prevention and treatment trials.ObjectiveTo investigate whether female participants and racial and ethnic minority individuals are adequately represented in COVID-19 prevention and treatment trials in the US.Data SourcesIdentified studies were registered on ClinicalTrials.gov or published in the PubMed database from October 2019 to February 2022.Study SelectionIncluded studies must have provided the number of enrolled participants by sex, race, or ethnicity. Only interventional studies conducted in the US for the primary purpose of the diagnosis, prevention, or treatment of (or supportive care for) COVID-19 conditions were included.Data Extraction and SynthesisData on counts of enrollments by demographic variables (sex, race, and ethnicity) and location (country and state) were abstracted. Studies were broadly categorized by primary purpose as prevention (including vaccine and diagnosis studies) vs treatment (including supportive care studies). A random effects model for single proportions was used. Trial estimates were compared with corresponding estimates of representation in the US population with COVID-19.Main Outcomes and MeasuresSex, racial, and ethnic representation in COVID-19 clinical trials compared with their representation in the US population with COVID-19.ResultsOverall, 122 US-based COVID-19 clinical trials comprising 176 654 participants were analyzed. Studies were predominantly randomized trials (n = 95) for treatment of COVID-19 (n = 103). Sex, race, and ethnicity were reported in 109 (89.3%), 95 (77.9%), and 87 (71.3%) trials, respectively. Estimated representation in prevention and treatment trials vs the US population with COVID-19 was 48.9% and 44.6% vs 52.4% for female participants; 23.0% and 36.6% vs 17.7% for Hispanic or Latino participants; 7.2% and 16.5% vs 14.1% for Black participants; 3.8% and 4.6% vs 3.7% for Asian participants; 0.2% and 0.9% vs 0.2% for Native Hawaiian or Other Pacific Islander participants; and 1.3% and 1.4% vs 1.1% for American Indian or Alaska Native participants. Compared with expected rates in the COVID-19 reference population, female participants were underrepresented in treatment trials (85.1% of expected; P < .001), Black participants (53.7% of expected; P = .003) and Asian participants (64.4% of expected; P = .003) were underrepresented in prevention trials, and Hispanic or Latino participants were overrepresented in treatment trials (206.8% of expected; P < .001).Conclusions and RelevanceIn this systematic review and meta-analysis, aggregate differences in representation for several demographic groups in COVID-19 prevention and treatment trials in the US were found. Strategies to better ensure diverse representation in COVID-19 studies are needed, especially for prevention trials.

Axes of social inequities in COVID-19 clinical trials: A systematic review

“…This might be explained by the public policies and guidelines from the National Health Institute to enhance the participation of racial and ethnic groups and other minorities in clinical trials (36). However, reporting does not necessarily imply better representativeness, as suggested by a recent study that found underrepresentation of Black and Asian groups in trials about COVID-19 prevention (37). The representativeness of a trial not only depends on who is included, but also on who completed the follow-up (38).…”

Factors Associated With Enrollment into Inpatient Coronavirus Disease 2019 Randomized Controlled Trials: A Cross-sectional Analysis

“…The underrepresentation has even persisted in large-scale US-based COVID-19 trials, including the phase 3 Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies trial (NCT04427501) for the monoclonal antibody combination bamlanivimab plus etesevimab, in which only 12.6% of patients self-identified as non-White [ 15 ], and the Pfizer-BioNTech and Moderna vaccine trials in which patients self-identifying as non-White represented 18.1% and 20.6% of the trial cohorts, respectively [ 12 ]. Furthermore, in a systematic review and meta-analysis of 122 US-based COVID-19 trials, Xiao et al described aggregate differences in trial representation relative to COVID-19 incidence between racial/ethnic groups in both vaccine and treatment studies [ 13 ]. Amid a global pandemic that disproportionately affects communities of color [ 18 ], opportunities for early access to potentially effective treatments through trials, coupled with the need for findings that are generalizable to those bearing the greatest burden of COVID-19, necessitate diverse trial enrollment and the addressing of factors that discourage participation by underrepresented groups.…”

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“…The underrepresentation of minoritized groups in health research is well established (18)(19)(20). The reasons for this lack of representation are not singular; they can be attributed to distrust of health research, lack of opportunity, and structural barriers.…”