COVID-19 trials risk excluding those most vulnerable to virus
The elderly and communities of color have suffered disproportionately from the COVID-19 pandemic — and those groups are also at risk of being short-changed by fast-paced clinical trials with participants that skew younger and whiter than the general U.S. population.
Older adults may be willing to participate in research but may not be appealing candidates to drug companies, due to their poorer underlying health. People from minority groups may be less inclined to trust the system, given historical injustices and a lack of diversity among the people actually conducting the research.
Experts warn that many COVID-19 studies are likely excluding the elderly and that medical researchers still have a long way to go before minority communities more actively participate.
"We can't just go to Black and brown communities and say, 'Sign up for clinical trials, participate in clinical trials,' if there is not deep representation upstream in the science and the management of the processes that bring about the science," Michelle A. Williams, dean of the Harvard T.H. Chan School of Public Health, said in a Journal of the American Medical Association interview last week.
Only two companies in large-scale vaccine testing have publicly reported participants' demographics. The data fall short of an ideal level of diversity, and information on age groups is too limited to be helpful, experts say.
Pfizer Inc. says it will likely be the first company to report results, probably in mid-November. The company's trial is the largest; it's aiming for 60,000 enrollees and as of Monday, had recruited nearly 40,000, with approximately 34,600 so far receiving both required doses.
The company also is providing the most detail about its trial participants. Among U.S. participants, 10 percent are Black and 13 percent are Hispanic.
Pfizer's trial doesn't quite reflect the U.S. population or the population afflicted with COVID-19. According to the Census Bureau, approximately 13 percent of the population is Black and 18.5 percent is Hispanic. Since May, 19 percent of COVID-19 deaths were among Black people and 24 percent were among Hispanic people, according to a CDC study published Friday.
Among the COVID-19 cases for whom ethnic background data was available, 17.4 percent were Black and 28.1 percent of cases were Hispanic.
The vaccine from Moderna Inc. is in the same development stage, with results anticipated by late November. The company had enrolled more than 29,500 participants in its 30,000 person study as of Friday, and said approximately 36 percent are from "diverse communities." It didn't provide more specific information about participants' ethnicity or age.
While COVID-19 cases come from all age groups, nearly 95 percent of the deaths were from people aged 50 or older, and risk increases by age, underscoring how important it will be to protect seniors. Some vaccine trials have an explicit age cut-off, while others may have other criteria that could result in seniors' exclusion.
A recent JAMA study looked at hundreds of clinical trials, finding around half had such exclusions. Among 18 vaccine trials, 11 had an age cut-off — and all were "considered high risk for excluding older adults."
Sharon Inouye, a Harvard Medical School professor of medicine and an author of the JAMA study, told CQ Roll Call that a lack of inclusion could make it harder to know if seniors are getting the right vaccine dosage or face increased risk of adverse side effects.
Inouye and her co-authors acknowledged that some exclusions are appropriate to protect older adults, but said that generally, researchers need to avoid restrictions that could exclude mostly healthy older adults, like having high blood pressure or requiring communications with researchers via text messages.
Inouye, also a geriatrician at Hebrew SeniorLife, a Boston-based geriatric care provider, worries that in the rush to develop vaccines and treatments, some companies or researchers simply find it easier to exclude older adults.
When conducting studies in nursing homes, she said, "we deliver educational materials, we hold talks with the staff, we hold talks with the patients, and their families, and we have hotlines set up to get your questions answered, and I just don't know if all of those steps are being done."
Pfizer may have more seniors than many trials, since it reported that nearly half of its U.S. participants are between the ages of 56 and 85.
But without a more specific breakdown, it's hard to conclude much from that statistic, given the wide gaps in health status between people in their 50s and people in their 80s, said Inouye.
Another recent report examined six U.S.-based trials of two drugs that have been studied as potential COVID-19 treatments: remdesivir and hydroxychloroquine. Among the studies that reported race and ethnicity, in most cases they did not represent the ethnic makeup of the cities where they were conducted. In a Minneapolis-based study, Black participants were 5 percent of the study population versus 33 percent of cases, and Hispanics were 5 percent of the study compared to 28 percent of cases.
Consequences of distrust
The lack of representation could have repercussions once a vaccine is approved. A significant portion of Black Americans already say they wouldn't take an approved vaccine, according to a recent poll from the Kaiser Family Foundation and news outlet The Undefeated. The poll found that roughly 50 percent of Black Americans said they likely wouldn't get a COVID-19 vaccine, even if it was free and determined to be safe, compared to 37 percent of Hispanics and 33 percent of whites. Roughly two-thirds of Black respondents said they weren't confident that the development process takes the needs of Black people into account.
If large numbers of Americans refuse to take a vaccine, that could prevent immunity among the population from building and allow the coronavirus' spread to continue longer.
Researchers are trying to address a lack of diversity but experts say it will take time.
Stephaun Wallace, director of external relations for a network trying to recruit patients for COVID-19 trials at Seattle's Fred Hutchinson Cancer Research Institute, said outreach to underrepresented communities, partnerships with trusted community groups, culturally-sensitive staff and welcoming and accessible trial sites are important. But he said it will also take more commitment to reckon with the reasons for the distrust, like historical instances of research abuses involving Black participants. He also said it's important to have more representation among the people conducting the research.
"I don't imagine that this process will happen overnight by any stretch of the imagination," he said. So far, among the 430,000 volunteers who volunteered to participate in a clinical trial through the Fred Hutch network, just 11 percent identify as Black/African American or Latino.
Congress in recent years took steps to try to promote trial diversity through the National Institutes of Health, where grantees are generally required to try to have representative participants. The agency also has sought to promote younger and more diverse groups of researchers.
But Ellie Dehoney, vice president of policy and advocacy at Research!America, a nonprofit that advocates for health research funding, said it's important to respect the reasons that groups distrust the health system— including how the COVID-19 response might have sown added distrust.
"One of those reasons is that the response to these awful disparities in death rates, particularly, came so slowly," she said.