Early coronavirus drug trials tested vaccines mostly on White people; next phase aims for diversity
- The first large-scale clinical trials of Covid-19 vaccines in the U.S. got underway this week.
- Communities of color are among priority groups for enrollment given the disproportionate toll of the disease.
- More than 150,000 people have already expressed interest, but ensuring diversity is a challenge.
With chronic asthma, food allergies and a heart condition, Thomas Silvera does everything he can to safeguard his health, including getting vaccines. So if and when a Covid-19 vaccine becomes available, he said, he's leaning toward getting that, too.
But before vaccines reach the market, they go through wide-scale testing for safety and efficacy. The first two trials in the U.S. officially started Monday, from drug companies Moderna and Pfizer.
Silvera, 44, said he's less likely to try a vaccine as part of a clinical trial.
"I would wait for a more robust data analysis," said Silvera, who is a certified surgical technologist. He noted he'd especially want to know the long-term effects for people with asthma first.
As someone with pre-existing health conditions and who is both African American and Hispanic, Silvera might be exactly the kind of participant clinical trial organizers are looking for. The Covid-19 Prevention Network, formed by the National Institutes of Health, is prioritizing enrolling people at highest risk of the disease into the late-stage clinical trials: those with underlying health issues, the elderly, essential workers as well as the Native American, Latino and Black communities.
"We really need to be incredibly mindful of reaching out to those communities who are hardest hit to ensure that we are getting individuals who are at heightened risk," said Michele Andrasik, a clinical assistant professor of global health at the University of Washington and director of community engagement for the Covid-19 Prevention Network.
Racial and ethnic minorities are not only getting Covid-19 at higher rates but also having worse outcomes, studies have shown.
Silvera said many in his community may be hesitant to enroll in clinical trials.
"It's all about trust and not seeing that this vaccination is going to be another experiment on them," he said.
The issue of medical mistrust among communities of color "is entirely justified, if you go way back," said Linda Goler Blount, chief executive officer of the Black Women's Health Imperative.
History of experiments
She pointed to J. Marion Sims, a gynecologist who experimented on enslaved women, and Henrietta Lacks, whose cells were taken without her family's knowledge in 1951 and then used to develop everything from the polio vaccine to in vitro fertilization. Goler Blount also noted the Tuskegee study, in which Black men with syphilis were not offered treatment for decades after penicillin became available in the 1940s, so that government researchers could study the long-term effects of the disease.
"What happens is this is in the lore," Goler Blount said. "So even though there are African Americans who weren't even alive when Tuskegee was happening, they hear about it. And they have their own experiences of doctors not recommending certain treatments, or being mistreated in the medical setting."
Inclusion in clinical trials matters to ensure drugs or vaccines work for everyone who needs them. Goler Blount pointed out this can mean some medicines aren't as effective for certain groups.
"Historically, people of color have been left out of clinical trials," she said. "And we've seen plenty of examples of where drugs have been developed or therapeutics developed and it turns out they don't work as well in communities of color."
She cited research that shows dexamethasone is a promising treatment for Covid-19. It's a steroid that's commonly used as an anti-inflammatory drug to treat asthma and allergies, among other things. But dexamethasone works differently in Black people, and the clinical trials looking at it as a Covid-19 treatment may not have included enough minorities to ensure it's safe for them, according to Johns Hopkins Medicine pharmacologist Namandje Bumpus.
Vaccine trials in particular are sometimes "done in relatively healthy populations, middle-aged, sometimes more geared toward men, White men," said Aisha Langford, an assistant professor in the department of population health at New York University's School of Medicine. "There's nothing wrong with that, but if you're a middle-aged Black woman and you're someone who is 75 years old who could get some of these very same conditions that are being studied in clinical research, you won't really know how, if at all, there are any differences in response."
Leaders of the Covid-19 Prevention Network agree.
"If we're going to make a vaccine that works for all of us, we need to be able to make sure that all of those key populations are included," said Dr. Nelson Michael, who's director of the Center for Infectious Disease Research at the Walter Reed Army Institute of Research and is part of the Trump Administration's Operation Warp Speed.
The earliest human studies of Covid-19 vaccines didn't prioritize racial diversity.
In the Moderna trial, run by the National Institute of Allergy and Infectious Diseases, or NIAID, 40 of 45 participants were White, while Oxford University researchers noted the findings of their initial trial with AstraZeneca "are not easily generalisable, as this is a first-in-human study of fairly young and healthy volunteers, the majority of whom were White."
A spokeswoman for AstraZeneca, which is partnered with Oxford on its Covid-19 vaccine, said the larger clinical trials will include participants "drawn from diverse populations" and that its clinical trial sites "will focus on areas where there is a high amount of disease present and where we know the vaccine disproportionately impacts populations that are typically underrepresented in clinical trials."
Pfizer and BioNTech, which also began a late-stage clinical trial of their Covid-19 vaccine in the U.S. this week, made a similar note about their early study population and plans for phase three.
The NIAID said its phase one trial of Moderna's vaccine did not target a specific ethnicity. So the population enrolled reflects those who responded to recruitment at participating sites and who met the trial's inclusion criteria.
But it's a key priority in the phase three, which plans to enroll 30,000 participants and which began Monday in the U.S.
"I'm not worried about being able to recruit people into these trials; I'm worried … about recruiting the right people," Moderna Chief Medical Officer Dr. Tal Zaks said in a panel discussion organized by the New York Academy of Sciences in late June.
"I live in Newton, Massachusetts, and if I were to launch a site here, people would line up around the block and we'd have the trial recruited in two days," he said. "But you'd find people like me, who are sitting at home all day and who have the luxury of being able to distance."
Zaks said he's asked his team to update him regularly on the makeup of the trial "and to be clear to investigators that if the diversity isn't representative, we will stop enrolling at those sites … and we will preferentially enroll at places that are able to reach out to those populations."
Asking is the first step
Goler Blount, of the Black Women's Health Imperative, said plans for inclusion are the first step.
"The No. 1 reason Black people and Brown people don't participate in clinical trials is because nobody asks them," she said.
That can be because health providers "make certain assumptions about what patients will and will not do: They won't comply. They don't have the money," Goler Blount said. "So they don't ask."
And having the flexibility to be able to participate in clinical research is a consideration, said Dr. Lisa Cooper, Bloomberg Distinguished Professor of Equity in Health and Healthcare at Johns Hopkins Medicine.
There are "day-to-day challenges that would get in the way of doing something like participating in research," Cooper said. "It's something you would do as a volunteer. It's a luxury to have the time to do something like that."
But, NYU's Langford noted, "more recent studies have shown that when people are invited and actually offered to participate, sometimes you see those disparities reduce or go away."
Those working on the phase three vaccine trials are now focused on establishing that access for priority communities and building trust.
Dr. Richard Novak, the lead investigator at the University of Illinois at Chicago for Moderna's Covid-19 vaccine trial, said his team plans to reach out to African-American churches, as well as warehouse and meatpacking facilities where there have been large outbreaks.
"We are using a mobile clinic that will allow us to go to specific sites and enroll large numbers of people on site," he said.
Andrasik, who leads community engagement for the Coronavirus Prevention Network, said they're building on work done on HIV, which has "vast" similarities with Covid-19.
"We are very accustomed to working within a framework where people are stigmatized and where they are disproportionately impacted because of some of the social and structural factors that impact their communities," she said.
Since the network's website, which has a link for people to volunteer for the clinical trials, was posted on July 8, more than 150,000 people have expressed interest, she said — and that was before they started any outreach campaigns. But Andrasik said she didn't yet know how many of those people come from the priority groups.
"People have to feel that this is something that is good for them and their community," Andrasik said. "So building trust is really key. And that doesn't happen overnight."
Source: Read Full Article