Women, Minorities Underrepresented in US COVID-19 Clinical Trials

Hong Xiao, PHD

Patient sociodemographic diversity—a core issue in many US clinical trials—is not representative of the general population in COVID-19 studies, according to a new analysis.

In data from a systematic review and meta-analysis of US-based COVID-19 clinical trials, a multinational team of investigators observed underrepresentation of female, Black and Asian participants compared to the expected rates of the virus in these populations. Interestingly, the findings also showed an overrepresentation of Hispanic or Latino participants in these clinical trials.

Led by Hong Xiao, PhD, of the Fred Hutchinson Cancer Center in Seattle, investigators sought to interpret female and racial/ethnic minority representation across US trials assessing COVID-19 prevention and treatment strategies. COVID-19 has been repeatedly observed to disproportionately impact racial and ethnic minority groups in outcomes including incidence, hospitalization and death. There’s also been discernible outcome differences based on gender and sex, as well as variation in drug and vaccine efficacy and effects based on patient demographics.

“Prevention and treatment regimens shown to be effective in clinical trials cannot be confidently applied to all populations when individuals with diverse backgrounds are not adequately represented,” investigators wrote. “However, clinical trials have often lacked equitable inclusion of female participants and individuals identifying as members of specific racial and ethnic groups, including Black, Hispanic, and Native American.”

Xiao and colleagues conducted their analysis including US-based clinical trials that included numbers of enrolled patients based on sex, race or ethnicity. The trials had to include an intervention being assessed for the primary use of diagnosing, preventing or treating COVID-19-related conditions.

They then stratified studies by primary purpose of prevention—including vaccines and diagnostics—versus treatment—including supportive care methodology.A random effects model for single proportions was used to interpret relative demographic representation.

The final analysis included 122 clinical trials including 176,654 participants. A majority of trials (n = 103) regarded COVID-19 treatments, and included randomized populations (n = 95). Patient sex was reported in 109 (89.3%) trials; race was reported in 95 (77.9%); and ethnicity was reported in 87 (71.3%).

Among prevention and treatment trials, estimated representation for female participants weas 48.9% and 44.6%, respectively—compared to the US population representation of 52.4%. Among Black participants, estimated representation was 7.2% and 16.5%, respectively, versus 14.1% of the US population. Among Asian participants, rates were 3.8% and 4.6% versus 3.7%; among Hispanic or Latino participants, rates were 23.0% and 36.6% versus 17.7%, respectively.

When comparing the expected rates in the COVID-19 reference population, investigators noted that female participants were underrepresented in treatment trials (85.1% of expected; P <.001). Black (53.7% of expected; P = .003) and Asian participants (64.4% of expected; P = .003) were underrepresented in prevention trials.

However, Hispanic or Latino participants were overrepresented in treatment trials by more than two-fold (206.8% of expected; P <.001).

Investigators wrote the findings highlight “the ongoing struggle in the US to provide equitable access to clinical studies regardless of an individual’s demographic background.”

“This analysis reaffirms prior evidence that industry-sponsored trials enrolled fewer racially diverse participants compared with federally sponsored trials,” they wrote. “Industry-sponsored trials have not been subject to NIH mandates regarding proportional racial representation. Because the majority of COVID-19 vaccination and treatment trials are industry sponsored, and pharmaceutical companies contribute the most to production, marketing, and distribution of novel therapeutics and devices, poor representation of racial minority groups is of vital scientific interest and has unique implications for disparities in treatment efficacy, adverse effects, and access.”

They called for additional strategies to ensure COVID-19 clinical trial sponsors are more accountable for appropriate representation of both female and racial and ethnic minority individuals.

The study, “Sex, Racial, and Ethnic Representation in COVID-19 Clinical Trials,” was published online in JAMA Internal Medicine.