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Seldom does a vaccine researcher’s job include calling city hall, big-box stores like Walmart and Target, and the US Postal Service. But Ann Falsey, MD, had those tasks on her to-do list in June as she prepared to recruit volunteers to test potential vaccines for coronavirus disease 2019 (COVID-19).
Falsey, of the University of Rochester School of Medicine, hoped large employers in her area would publicize vaccine trials to their essential workers, many of whom are Black or Hispanic.
“We are thinking very hard about not only how to get a diverse population that reflects the US population but also people at high risk—postal workers, home health workers, you name it,” she said.
COVID-19’s startling toll on minorities has drawn widespread attention to the need for diversity in large-scale phase 3 vaccine trials. Two 30 000-person trials, led by Moderna and a joint effort of Pfizer and BioNTech, began on July 27. AstraZeneca was expected to start US recruitment to test its vaccine, developed with Oxford University, in August, followed by Johnson & Johnson in September and Novavax later this fall.
Drawing tens of thousands of people of color into clinical trials would be a heavy lift anytime in the US health care system, which is rife with distrust and racial divisions. But social distancing due to the pandemic—along with social unrest sparked by the police killing in Minneapolis of George Floyd—are adding to the challenge.
Tried-and-true outreach strategies such as talks at community gatherings are off the table, replaced by Facebook posts, Zoom calls, and news media interviews. “We can’t just go hang up posters,” Falsey noted.
An “Extreme” Burden
At a Senate hearing in July, Francis Collins, MD, PhD, director of the National Institutes of Health (NIH), observed that some minority communities bear an “extreme” burden from COVID-19. Data from multiple sources illustrate the point.
The Centers for Disease Control and Prevention (CDC) has reported that non-Hispanic American Indian or Alaska Native individuals are hospitalized with COVID-19 at 5.3 times the rate of non-Hispanic White people. For Hispanic populations and non-Hispanic Black individuals, the rate is 4.7 times higher.
According to the COVID Racial Data Tracker, a collaboration between The Atlantic and Boston University’s Center for Antiracist Research that compiles data from state and local health authorities, Black people die at nearly 2.5 times the rate of White people; Hispanic and American Indian or Alaska Native individuals die at about 1.3 times the rate of White people.
People of color are also 3 times more likely to become infected with the novel coronavirus, according to New York Times reporting based on demographic data that the newspaper sued the CDC to obtain. Experts interviewed for the article noted that Black and Latino individuals are at higher risk because they more frequently live in crowded, multigenerational homes and hold jobs they can’t do remotely. The Times reported that Latino adults aged 40 to 59 years have been infected at 5 times the rate of White adults of the same age.
Meanwhile, studies show persistent minority underrepresentation in clinical trials, even for conditions that affect them disproportionately. As recently as May, a study in the Journal of the American Heart Association showed Black people accounted for only 4% of 300 000 participants in trials of cardiovascular and diabetes medications approved by the US Food and Drug Administration (FDA) from 2008 to 2017, and Hispanic individuals accounted for 11%.
A study published in June in Cancer Epidemiology, Biomarkers & Prevention showed that White men accounted for a whopping 96% of participants in prostate cancer trials from 1987 to 2016, with little change over time.
Although publicly funded trials tend to be more representative than those sponsored by drug companies, even minority enrollment in some federally funded trials has lagged. That’s been the case despite the NIH Revitalization Act of 1993, which required the agency to take steps such as conducting outreach and ensuring that trials are designed to provide valid results showing whether minorities are affected differently than other participants.
According to NIH data for fiscal 2019, 30% of participants in US NIH-funded clinical research identified as racial or ethnic minorities, including 16% Black, 9% Hispanic, 3% Asian, 2% more than one race, 1% American Indian or Alaska Native, and 0.2% Native Hawaiian or Pacific Islander. An NIH media official said in an email that the agency has policies to increase minority representation and noted that appropriate levels of racial and ethnic representation vary for each study.
Federal Scientists Push for Diversity
A push for diversity in COVID-19 vaccine trials came from top government scientists who appeared before a Senate subcommittee in July to answer questions about the Trump administration’s Operation Warp Speed vaccine effort. They stressed the importance of having data to show that vaccines are safe and effective in populations hardest hit by the virus.
“The last thing we want is to be trying to recommend who gets the vaccine and we don’t have any data on how the vaccine works in the population” that needs it, CDC Director Robert Redfield, MD, said during the hearing.
Although Collins testified that it would be “much easier to line up a whole bunch of 20-somethings who happen to be from the White population,” he acknowledged that doing so wouldn’t meet the country’s needs. Testing vaccines with a diverse population is “our responsibility as stewards of the public trust,” he noted.
The FDA signaled in late June that it wants safety and efficacy data for diverse populations as it determines whether to allow vaccines on the market. The agency released nonbinding guidance saying it “strongly encourages the enrollment of populations most affected by COVID-19, specifically racial and ethnic minorities.”
Within weeks after joining in a stakeholder call with the FDA, the Alliance of Multicultural Physicians in June wrote to the agency’s commissioner, Stephen Hahn, MD, and members of Congress to call for diversity in COVID-19 trials including “clinically meaningful data to address the needs of a diverse America.”
Yet government scientists said in interviews that the discussion about including minorities in COVID-19 vaccine trials began as far back as March, predating protests over Floyd’s death in late May, which drew more attention to US health disparities.
The protest movement “makes it more poignant,” Falsey said. “We need to do better.”
Vaccine safety and efficacy may not differ based on a person’s race, although researchers said they’ll keep such outcomes on their radar. It’s more likely that vaccine protection will vary according to different ages, immune responses, and comorbidities. That’s important for racial and ethnic minorities who are known to have higher rates of underlying diseases such as obesity, chronic lung disease, and diabetes.
To help them connect with minority communities, investigators have drawn upon a range of experts, including the NIH’s own National Institute on Minority Health and Health Disparities as well as academic medical centers that serve large minority populations. In early July a website launched by the National Institute of Allergy and Infectious Diseases (NIAID) went live to educate potential volunteers.
Investigators also are leveraging strategies cultivated though decades of HIV research, such as partnering with Black churches and other trusted community leaders and hiring diverse staffs. Some vaccines in the Operation Warp Speed effort will be tested through the COVID-19 Prevention Trials Network, which combines the expertise of 4 NIAID-funded trial networks, 3 of which focus on HIV and AIDS.
The same principals of inclusiveness applied to HIV will be used for COVID-19 vaccine studies, Larry Corey, MD, of the Fred Hutchinson Cancer Research Center in Seattle, Washington, said in an interview. After helping to found the international HIV Vaccine Trials Network in the late 1990s, Corey now coleads the COVID-19 trial network.
The pharmaceutical industry also feels pressure to include people of color in COVID-19 vaccine clinical trials.
In April, 15 Democratic US senators sent letters to pharmaceutical companies saying trials for COVID-19 vaccines and drugs “must include participants that racially, socioeconomically, and otherwise demographically represent the United States.”
The topic also has come up in government researchers’ meetings with industry officials. Collins said that as Moderna was preparing to launch the first phase 3 trial in the US, he made it clear to the company’s leadership that “diversity is not optional.”
Companies say they want to include minorities in research—both the Pharmaceutical Research and Manufacturers of America and the Biotech Innovation Organization (BIO) stated in emails that they’re committed to encouraging diversity in COVID-19 vaccine trials.
Michelle McMurry-Heath, MD, who on June 1 became the first Black individual and the first woman to lead BIO, pointed to a partnership with the Clinical Trials Transformation Initiative (CTTI), which hosted a webinar on ways to engage minority communities about COVID-19 clinical trials.
But drug companies sometimes lack the know-how to effectively recruit people of color, said Marjorie Speers, PhD, of Clinical Research Pathways, an advocacy group funded partly by industry to expand clinical trial diversity by increasing the number of minority investigators.
In addition, Speers added, minority recruitment is expensive, entailing costs to hire culturally competent outreach specialists and patient navigators as well as to provide special educational materials, transportation, and childcare. A 2003 Mayo Clinic study found a nearly 5-fold higher cost to recruit minority participants than Whites.
During a July 21 congressional hearing, 4 companies involved in vaccine development—AstraZeneca, Moderna, Pfizer, and Johnson & Johnson—said that diversity is a priority in their work. However, only the Johnson & Johnson representative mentioned any specifics. Macaya Douoguih, MD, MPH, head of clinical development and medical affairs for vaccines, said the company plans to use digital and community outreach while evaluating ways to reduce barriers to participation at individual trial sites.
A Lack of Confidence
Perhaps the biggest hurdle is that many people of color don’t believe the health care system will act in their interest. Memories of abusive research practices, including the government’s notorious Tuskegee syphilis study that ended in 1972, are “still alive and well in people’s memory,” said Sandra Crouse Quinn, PhD, a professor at the University of Maryland School of Public Health in College Park, who has studied cultural factors in vaccine racial disparities.
Polls show that Black individuals are less trusting of medical research than White or Hispanic people, including their attitudes about vaccines. In a Pew Research Center survey conducted in late April and early May, 54% of Black adults said they definitely or probably would get a COVID-19 vaccine compared with 74% of White and Hispanic adults.
Yet participating in trials could build vaccine confidence in communities that are most vulnerable to the virus by generating data that demonstrate safety and efficacy for people like them, noted Oliver T. Brooks, MD, president of the National Medical Association, which represents Black physicians.
“I need to be able to go to my African American community and speak with confidence and authority” that a COVID-19 vaccine is safe and effective for them, said Brooks, a pediatrician and a past president of the California Immunization Coalition and chairman of the Immunize LA (Los Angeles) Families Coalition.
In the wake of Floyd’s killing, however, Collins said racial tension may make it more difficult to convince Black communities to participate in a government program.
Using trusted community messengers may help, as would having more minority researchers conducting the trials. The nation’s 4 historically Black medical schools have been enlisted as COVID-19 vaccine trial sites. They include Meharry Medical College in Nashville, Tennessee, where President James E.K. Hildreth, MD, PhD, said in an interview that he plans to be first to roll up his sleeve.
Hildreth said he would like to participate as an investigator but thinks it’s more important to set an example to counteract what he called “visceral” fears of vaccines. “I want to be able to say, ‘I am participating. I need you to do the same.’ That will be very compelling for some people,” he said.
Hispanics’ Multifaceted Fears
Hispanic communities harbor additional fears about running afoul of immigration authorities.
As “an immigrant minority that’s not being treated very well in our country right now,” Hispanic people worry about more than the risks of receiving an experimental vaccine, said Milagritos Tapia, MD. “It’s the additional risk of exposing yourself to the system,” added Tapia, a professor of pediatric infectious diseases at Baltimore’s University of Maryland School of Medicine.
And as today’s cultural dynamics collide with the Trump administration’s goal of getting a vaccine on the market early next year, Tapia is among those scrambling to build bridges between researchers and potential trial volunteers.
After the pandemic grounded her from traveling to Mali for vaccine development work, Tapia took on the task of reaching out to local Hispanic leaders in preparation for vaccine trials. Her institution planned to enroll several hundred people in Moderna’s trial.
She’s knocked on a lot of doors, guided by her knowledge of local communities. Facebook page managers were willing to lend their platforms to publicize trials, and a police detective provided contacts at an agency focused on Latino health care, whose field workers might urge their clients to participate in trials.
She’s also handled tough questions. Community leaders wanted to know whether undocumented residents would be in legal jeopardy if they participated in a trial, and who would pay medical expenses if a participant got sick. They also asked the ultimate question: if the vaccine they help test is approved, will people in the community have access to it?
Although CDC officials have considered whether vulnerable minorities will be prioritized to receive a vaccine, Tapia said her message for potential volunteers is that she has no control over the matter. However, she noted, “we certainly would use everything in our power to advocate for that.”
Navigating the Technicalities
Other barriers exist, as well. Although potential NIH grantees must include information on their minority recruitment plans in their applications, Collins said the agency has less direct control over private contract research organizations that manufacturers may hire to help recruit some of the 30 000 or more people needed for each phase 3 trial.
There’s also no clear benchmark for success. The FDA hasn’t specified how much minority representation it wants to see, and Collins said there’s no general agreement on the percentage of minorities that trials should include. Some scientists would contend that participants should reflect the burden of disease. However, Collins said hard-hit minorities should be represented at least in proportion to their percentage of the US population, if not more. That’s 13% for Black people and 18% for Hispanic individuals.
Another big hurdle is that hotspots can change quickly. Areas where the virus is rampant are the most efficient testing grounds to quickly determine whether vaccinated volunteers are being infected at lower rates than those who received a placebo.
The NIH and trial sponsors will choose sites just weeks before each trial begins, based on where the virus is most prevalent, Collins said. Researchers then will have to “kick into very high gear” to recruit in those zip codes, he added.
It’s possible that hotspots will emerge in locations with fewer minorities, such as colleges and universities. Or cities in other countries. Johnson & Johnson’s Douoguih said the company might extend recruiting to sites outside the US when its phase 3 trial begins in September.
If people of color aren’t enrolled in robust numbers, researchers can “try to catch up” by using surveillance data collected in phase 4 studies, which are conducted after a vaccine is on the market, said Nelson Michael, MD, PhD, director of the Center for Infectious Disease Research at the Walter Reed Army Institute of Research in Silver Spring, Maryland.
But with that approach, it could take years for safety problems to become apparent, added Nelson, who is advising Operation Warp Speed’s vaccine development team.
Given the rate at which they are getting sick and dying, Brooks said people of color don’t have the luxury of time. “We can’t wait for years,” he said.
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Jaklevic MC. Researchers Strive to Recruit Hard-Hit Minorities Into COVID-19 Vaccine Trials. JAMA. 2020;324(9):826–828. doi:10.1001/jama.2020.11244
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