Large U.S. covid-19 vaccine trials are halfway enrolled, but lag on participant diversity
Moderna and Pfizer, the companies leading the U.S. race for a coronavirus vaccine, disclosed this week they have enrolled more than half the people needed for the 30,000-person trials that represent the final phase of testing. But only about a fifth of participants are from Black and Hispanic communities, which have been hit hardest by the virus — lagging what several experts said should be the bare minimum of diversity.
An online registry that people can use to express interest in the vaccine trials — a list of about 350,000 volunteers — had only about 10 to 11 percent Black and Hispanic people as of late last week, according to James Kublin, executive director of the federal HIV Vaccine Trials Network, based at the Fred Hutchinson Cancer Research Center in Seattle. The HIV trials network is being repurposed to test coronavirus vaccines.
“We are working a bit uphill, in the Sisyphean task to get the studies representing the diversity [of the U.S.] — and that goes into the historical legacy of not just discrimination, but of outright unethical medical practices” on minority communities, Kublin said.
Creating vaccine trials that, at minimum, mirror the racial and ethnic breakdown of the American population, which is about one-third total Black, Hispanic and Native American, has been a major focus — a necessity to make sure any vaccine works for everyone and is broadly accepted. Current enrollment numbers lag even that target.
And, in recent weeks, debate in scientific circles focused on how trials for a coronavirus vaccine need to go beyond simply reflecting the composition of the nation’s population. Instead, many scientists argue, enrollment efforts should reflect the disproportionate burden of disease, hospitalizations and deaths borne by Black, Hispanic and Native American communities.
“The intent is to make a vaccine safe and effective for all Americans. Since there’s disproportionate burden of disease, enrolling people based on census numbers is a minimal target. I personally don’t think we should go below that,” said Nelson Michael, director of the Center for Infectious Disease Research at the Walter Reed Army Institute of Research. Michael is working on community engagement for vaccine trials in Operation Warp Speed, the federal program to speed up development of vaccines and treatments.
“What I can tell you is that lots of people are spending lots of times, right now, trying to make sure we can move the needle away from that minimal target to something better than that,” Michael said.
According to the Centers for Disease Control and Prevention, the rate of coronavirus cases is more than 2.5 times higher among Black, Hispanic and Native American communities as in the White community, and hospitalization rates are 4 to 5 times higher. Death rates from covid-19, the illness caused by the coronavirus, are twice as high in Black communities and 1.4 times higher in Native American communities, compared with the White community.
Moderna, the biotechnology company partnered with the federal government to develop a coronavirus vaccine, disclosed on a Wednesday call with investors that it had enrolled 15,239 people in its trial. Blacks, Hispanics and Native Americans made up 19 percent of those participants, according to the company.
Pharmaceutical giant Pfizer is also more than halfway through enrollment, and 19 percent of the participants are Black or Hispanic, and 4 percent are Asian, Pfizer senior director of Vaccine Clinical Research and Development Nicholas Kitchin told a CDC advisory committee.
Leaders from both companies have said they are committed to trials that reflect the people at highest risk. Scientists say diversity matters critically for understanding how a vaccine is likely to perform in the real world.
“A question we always ask ourselves, when we do clinical trials, are how generalizable will results be to people who suffer from the disease?” said Onyema Ogbuagu, who is leading a study of the Pfizer vaccine at Yale New Haven Hospital. “If you did a study in a majority-White population with very little Black individuals, when we do get results from the study, it will always be a question: Does it work the same in Black [people] as compared to others? And that’s even more so for covid.”
The numbers illustrate the speed at which trials, which began administering first doses of a vaccine or placebo at the end of July, have moved. But they also lay out the urgent challenge in improving diversity in ongoing trials and to make it a priority in future studies. Such outreach typically takes time and requires building trust with communities that may distrust the medical system because of systemic racism and a legacy of research abuse against minorities.
HIV physicians and scientists, who have provided much of the federal infrastructure for the clinical trial effort, have been building relationships with some marginalized communities for decades, but a much wider swath of the population and older people are at risk for covid-19.
Hala Borno, a medical oncologist at the University of California at San Francisco, studied a handful of coronavirus clinical trials that disclosed racial data and found that Blacks were underrepresented. She said trials must reflect the diversity of the population and should strive for more.
“That’s sort of the bare minimum,” Borno said. “The reality is, the way that scientific research goes, is you need a sufficient sample to power your analysis, to determine there is a real difference for that population. You need to oversample racial and ethnic minorities.”
Peter Hotez, dean of the School of Tropical Medicine at Baylor College of Medicine, said he thinks U.S. coronavirus vaccine trials should at least have 35 percent representation among minority groups.
“Given that Covid-19 has disproportionately caused severe illness and deaths among Hispanic, African American, and Native American populations in the U.S., it’s of critical importance that vaccine trials adequately reflect this reality,” Hotez said in an email.
To increase diversity, recruitment at clinical trial sites that are mostly enrolling White people may slow while others intensify their efforts. Clinical trial sites are also planning to use mobile vans to go into communities, instead of forcing volunteers to travel to their sites — and are working on other forms of outreach.
“We do have a community engagement effort, and in a strange way all the community engagement and materials development such as TV ads, radio — these have taken longer than getting through some of these [scientific] steps with the vaccines,” Kublin said. “It’s very exasperating for me.”