Coronavirus has been deadlier for people of color, yet they go underrepresented in clinical trials: Study
In the nationally funded Adaptive Covid-19 Treatment Trial, which is testing the efficacy of the antiviral remdesivir, Black Americans accounted for 20% of the patient population
Racial and ethnic disparities in disease burden have gained the spotlight in the US during the coronavirus pandemic. However, despite disproportionately higher rates of Covid-19 infection, hospitalization and death among people of color, minority groups are significantly underrepresented in Covid-19 clinical trials for vaccines and treatment.
Researchers have found that among the Covid-19 treatment-related clinical research studies published in the US, a third did not report race or ethnicity data. Black patients were underrepresented in all studies relative to the affected population in the cities in which the studies took place. According to experts, trials need more people of color to generalize results to a larger US population.
"Inclusive therapeutic clinical research is an important mechanism for addressing disparities in health outcomes. Given that racial/ethnic disparities in Covid-19 disease burden and outcomes have emerged in the US, it is essential that all investigators uniformly report race/ethnicity data as well as attempt, in earnest, to obtain representativeness among study participants to ensure that we do not develop a further widening of the treatment gap during this pandemic," write authors from the University of California San Francisco, US, in the report published in Contemporary Clinical Trials Communications. They add, "There are about 221 Covid-19 clinical trials recruiting in the US. It is critical that they aim to achieve representation among participants."
For the analysis, all published Covid-19 treatment-related clinical research studies with participants in the US were identified. For each, the date published, treatment investigated, study design, race/ethnicity of participants, sample size and study site were recorded. The race/ethnicity demographics of confirmed coronavirus positive cases were identified utilizing online publicly available department of public health data. The researchers found that six studies, three observational and three randomized clinical trials, have been published to date with US participants. A subset reported race/ethnicity data in the publication. The investigators were able to obtain race/ethnicity data from one additional work by contacting authors directly.
The results were striking, says the team. In the New York City-based report, 11% of the study population were Non-Hispanic Black (Black) and 51% were Hispanic. The authors state that according to the New York Department, 30.5% of New York City’s cases were Black and 32.7% were Hispanic. Therefore Black patients were underrepresented in this study and Hispanic patients were overrepresented.
In the study based out of Boston, Black and Hispanic patients were underrepresented relative to the affected population in the city (Black: 23% (study) versus 38% (city burden); Hispanic: 17% (study) versus 26% (city burden). Similarly, Black and Hispanic patients in the Minneapolis-based study were also underrepresented compared to the affected population in the city (Black: 5% (study) versus 33% (city burden); and Hispanic: 5% (study) versus 28% (city burden), reveals analysis. Two of the six studies were conducted across multiple sites in the US and globally, so data describing city-level burden could not be obtained. The analysis further shows that in another study, Hispanic patients comprised 23.4% of the study, while 20.6% were Black and 12.6% were Asian. In another, Black patients were 10.5% and Asian patients were 10% of clinical trial participants; it did not report the proportion of Hispanic patients.
"We observed that, to date, race/ethnicity is not uniformly collected or reported in clinical research studies related to Covid-19 treatments. Among racial/ethnic data we were able to assess, Black patients were consistently underrepresented relative to their disease burden. Given that three of the six studies are retrospective observational research, these data may also suggest that there are disparities in utilization patterns of novel Covid-19 treatments based on race/ethnicity. However future research will need to examine this further," say investigators.
Another analysis also found that Covid-19 clinical trials lack diversity. According to the authors, in the nationally funded Adaptive Covid-19 Treatment Trial, which is testing the efficacy of the antiviral remdesivir, Black Americans accounted for 20% of the total patient population. In the Gilead-funded clinical trial of the drug, only roughly one out of every 10 patients given remdesivir were Black. Latinx and Native Americans comprised 23% of the former trial and less than 1% of the latter. The investigators emphasize that it is alarming that long-standing racial health disparities have been extended to Covid-19 clinical trials when racial and ethnic minority groups have so much to gain from this research, including the opportunity to receive life-saving treatment.
Authored by faculty from the University of Georgia (UGA) and the University of Colorado and pharmacists from Phoebe Putney Memorial Hospital in Albany, the findings have been published by the New England Journal of Medicine (NEJM). "The overwhelming majority of the patients in both of those large clinical trials were Caucasians. Knowing that African Americans die at a higher rate than Caucasians, can I say that this medication will work in them as well? Yes, they enrolled a bunch of patients, and yes they got these data out as fast as possible, but can we use this information to inform treatments in all patients?" questions lead author Daniel Chastain, a clinical assistant professor of pharmacy at UGA’s Albany campus.
The team argues that as the US strives to overcome the social and structural causes of healthcare disparities, it must recognize the underrepresentation of minority groups in Covid-19 clinical trials. They explain that the remdesivir trials showed patients given the drug recovered from Covid-19 slightly faster than those who received placebos, but Black, indigenous and people of color often experience more severe symptoms and complications from the disease. The modest benefit seen in time to clinical improvement with remdesivir may not be generalizable to minority populations, given the differences in disease severity and outcomes, and it remains undetermined whether they will respond as well to the medication, the authors caution.
"Why aren't we putting up the infrastructure for clinical trial sites in areas that were heavily hit by Covid-19? If we would've included Albany, those clinical trials would've been more diversified and would’ve been much more representative of what the coronavirus pandemic looks like in our area and throughout the US," writes Chastain.
According to the experts, the lack of diversity in these clinical trials may stem from long-standing medical distrust on the part of minority communities. But the problem may be compounded by cost (in particular, hidden costs for such requirements as fuel, parking, meals and lodging), poor health literacy, lack of information, language barriers, limited accessibility and implicit biases against minorities, they add.
Another possible explanation is the lack of diversity among principal investigators who can obtain funding "since such diversity might curtail bias in recruitment of participants from underrepresented populations," says the team. However, despite these barriers, federal law and National Institutes of Health (NIH) policy mandate inclusion of minorities in NIH-funded research, they emphasize. "Furthermore, NIH-defined phase 3 clinical trials are required to report outcomes stratified according to sex or gender and according to race and ethnicity unless data are presented to suggest that differences are unlikely to be observed. These requirements, as well as the principle of justice, demand equitable selection and enrollment of participants and detailed presentation of demographic data and outcomes," the findings state.
To provide the necessary data for generalizing efficacy and safety outcomes across racial groups, Covid-19 clinical trials must prioritize the inclusion of patient populations that reflect the demographics of the ongoing pandemic, especially in the US, and funding for scientists from underrepresented ethnic groups must be increased, suggests the report. "Appropriate random sampling and the expansion of clinical trial sites to vulnerable communities with high-risk patients would improve the representativeness of samples. Furthermore, standardized reporting of race and ethnicity categories would allow for improved assessment of the generalizability of evidence-based interventions," the investigators conclude.