COVID Vaccine Trials Offer Lessons For Improving Clinical Trial Diversity
By Deborah Borfitz
November 16, 2021 | Concerted effort was required to ensure equitable inclusion of Black, Indigenous, and People Of Color (BIPOC) communities in COVID-19 vaccine trials—a complete reversal relative to historic norms. It would have been an impossibility without temporarily slowing or halting enrollment of White individuals so that the demographic composition at final enrollment closely mirrored the larger U.S. population.
So says Michele Andrasik, Ph.D., senior staff scientist in the vaccine and infectious disease division at Fred Hutchinson Cancer Research Center. In the end, the vaccine trials would serve as a demonstration of what could be accomplished with purposeful community engagement to understand and address the roadblocks to the participation of minority groups—while also highlighting the need for future trials to have clear goals for BIPOC enrollment from the outset of study accrual.
Many of the strategies deployed for the COVID trials were borrowed from the HIV Vaccine Trials Network (HVTN), funded by the National Institute of Allergy and Infectious Diseases (NIAID), where Andrasik is director of social & behavioral sciences and community engagement. Those methods have been successfully used for the past two decades to build meaningful, longstanding relationships with community leaders and organizers.
Importantly, she adds, HVTN ensures community members are at the table from concept generation to study results dissemination. “We are not just having people show up to fill a spot; we’re also making sure that they can meaningfully participate.” This includes introductory classes in immunology, vaccinology, and the protocol review process for lay audiences as well as skills training of scientists on how to share information with humility and authenticity.
Traditionally, BIPOC communities have been chronically underrepresented in vaccine trials, says Andrasik. And she believes that’s largely because it is relatively uncommon to ask community members for their input or train them how to review study protocols and get involved in the research process.
As extensively covered in a recent article in PLOS ONE (DOI: 10.1371/journal.pone.0258858), four COVID-19 vaccine efficacy trials (Moderna, AstraZeneca, Johnson & Johnson, and Novavax) decidedly emphasized enrollment of BIPOC individuals and it wasn’t happenstance. “There was a lot of pressure from us and from the funders [mostly the federal government] to ensure that the COVID-19 vaccine trials… represented the diversity of the American people,” says Andrasik.
“We knew, given the political and social climate, that even once we had a vaccine our work was still cut out for us in terms of acceptability and uptake, so having the trials represent the people most impacted was really critical,” she continues. This applied not just to racial and ethnic minorities but also to older adults and people who were experiencing more adverse health outcomes when they encountered SARS-CoV-2, such as those with preexisting health conditions.
The COVID-19 Prevention Network (CoVPN), formed by NIAID in response to the pandemic and headquartered at Fred Hutch, took the lead in ensuring diversity in vaccine trials and leveraged the infectious disease expertise of its existing research networks: HVTN as well as the HIV Prevention Trials Network (HPTN), Infectious Diseases Clinical Research Consortium, and AIDS Clinical Trials Group. The level of community input proposed was far beyond norms in the clinical trial ecosystem, and the changes needed to be implemented without haste, notes Andrasik.
“As soon as we found out we were pivoting to COVID, we reached out to all our longstanding partners and had conversations with them about how [the pandemic] was impacting their community… and, critically, what they felt we needed to do to ensure their equitable inclusion in the vaccine trials,” she says. Longer term, the plan was to “also ensure vaccine uptake and acceptability.”
The community partners identified by CoVPN to be part of community working groups were largely people who were already members of community advisory boards at NIAID-funded clinical research sites around the country, says Andrasik. The idea to create “expert panels”—one each for Native/Indigenous, Latinx, African American/Black, and Older Adults/VA)—originated from a conversation with professors from the University of Washington, Karina L. Walters (Choctaw Nation of Oklahoma) and Bonnie Durand (Opelousas/Coushatta descendent).
The expert panels, modeled after study review sessions of the National Institutes of Health (NIH), evaluated study protocols with an eye toward ensuring inclusion of priority populations, she says. Panelists were nominated by community partners and include scientists, advocates, and policymakers from around the country, all trained on how to review protocols before immediately applying that knowledge to the analysis of the government-supported COVID-19 vaccine trials.
During one- to three-hour meetings with each of the sponsors and protocol team leaders, panelists were provided with a high-level overview of the protocols and had their questions answered, says Andrasik. The panels then met as a group and wrote up their recommendations for ensuring inclusion of their population and ways to mitigate identified challenges.
Engagement of different priority communities in this manner needs to become more normative if clinical trials are to become more diverse moving forward, she says. But their involvement can’t stop there.
Clinical trialists need to have ongoing reciprocal relationships with different racial and ethnic groups, including White Americans, and work collaboratively to build each other’s capacity, says Andrasik. That requires funding to support community engagement even when trials are not actively enrolling. “I think a lot of people are starting to recognize why that is important, not only for diversity in our trials but to address amplified vaccine skepticism and hesitancy.”
All Hands On Deck
A subset of the expert panelists, representing diverse communities and geographies around the country, have opted to serve on a speaker’s bureau developed by CoVPN’s external relations team, reports Andrasik. They proved to be powerful voices against vaccine resistance and are now transitioning to addressing obstacles affecting HIV-related research.
Expert panelists also stressed the need to focus on social determinants of health, including the need to provide reimbursement for trial-related costs and address the burdens associated with traveling to study sites, she says. “We began early on to get a cadre of mobile units up and running [for use by clinical research sites] because one of the things we heard very clearly was that access to the sites, particularly in rural areas but also in urban areas where public transportation had been greatly reduced, was going to be an issue for individuals.”
At the same time, the CoVPN team began discussions with tribal leaders about data sovereignty and ownership, adds Andrasik. Those deliberations took a while—both the Moderna and J&J trials were fully enrolled by the time those contracts were in place—but is credited with the 8% American Indian/Alaskan Native participation rate in the Novavax vaccine efficacy study.
Educational materials drove COVID-19 vaccine inquiries to a website (PreventCOVID.org) where a volunteer screening registry was prominently featured, says Andrasik. With the click of a button, viewers could complete a pre-screening survey and that gave all U.S. vaccine trial sites access to the pool of volunteers living in a set of pre-determined local zip codes.
The registry database supported the enrollment of at least 30,000 people for each of the four CoVPN COVID-19 vaccine efficacy trials, and later swelled to many times that number for the benefit of other COVID-related trials. HVTN is now working on getting its own “red-ribbon registry” in place allowing anyone interested in HIV-related research to complete the pre-screening process.
“Much of the research we do in HIV contributes to oncology and other disease outcomes,” she notes, referencing HVTN’s quick and efficient pivot to COVID. The new registry, which is specific to NIAID-funded research opportunities, could launch before the New Year.
Training for working with minority communities, informed by CoVPN’s community partners, was offered to study sponsors and all CoVPN investigators, Andrasik says. Discussions focused on implicit bias and racial trauma, and the importance of using words that are inclusive and respectful. “The training is iterative, an ongoing practice… and something we have championed across the NIAID-funded network.”
Trusted voices were used to address questions and concerns about vaccine safety and side effects, equitable inclusion in vaccine trials, and the pace of vaccine development, she says. Critical to these efforts was outreach to essential worker organizations and corporations including nursing homes, assisted living facilities, and agricultural industries.
Attempts to engage managers and supervisors at meat packing plants were less successful, Andrasik adds. Information was delivered via email and publicly available drop boxes, but the relationships never “cemented” to the point where they became avenues for presenting webinars, town halls, and listening sessions. But efforts at making inroads continue with those future potential partners.
Conversely, a faith initiative was particularly impactful, continues Andrasik. It leveraged well-established relationships that HVTN has in faith communities, allowing information and resources about HIV to be shared in communities disproportionately impacted by the disease.
“We went from one faith ambassador in our HIV efforts to six faith ambassadors in COVID representing diverse belief systems and they held town halls and large educational sessions for different faith-based organizations, particularly those with health ministries. They were incredibly well received and helped us create materials that could be distributed… to inform people about the vaccines, why they shouldn’t wait and see, and how we were able to [develop] the vaccine so quickly without compromising safety or cutting corners.”
On top of an extensive multimedia campaign designed to address COVID-19 vaccine trial concerns (“Help End the Uncertainty”), CoVPN established a blog (“COVID-19 Vaccine Matters”) that as of March 2021 had 22,000 regular readers. The blog came in response to public requests for greater transparency about the clinical trials, explanations of the vaccine science in lay language, and to hear more directly from leading scientists, says Andrasik.
“One of the things about science is that it can be really confusing,” she notes, particularly when the media is focused on rare vaccine side effects such as myocarditis. “Data aren’t available as quickly as most people would like and sometimes can take you [in unexpected directions].” Increasing health and research literacy thus requires regular updates, being transparent about the knowns and unknowns, and, especially for parents faced with the vaccination decision, teasing apart the risks associated with getting vaccinated versus being infected with SARS-CoV-2.
This is not a self-correcting problem for vaccine trials of any stripe, she says. As Andrasik and her colleagues reported in a study published earlier this year in JAMA Network Open (DOI: 10.1001/jamanetworkopen.2020.37640), racial/ethnic minority groups and older adults have been underrepresented in such trials over the past decade so diversity enrollment targets are likely needed.
The NIH is currently reviewing request-for-funding applications from researchers with ideas about how to address vaccine hesitancy, which might most immediately help on the COVID front, Andrasik says. The projects funded should help point the way forward.
Better equity might also be achieved by conducting more population-specific trials, she adds, citing HPTN 091, the first HPTN study designed specifically and exclusively for transgender women, as an example.
For the larger clinical research community, the best first move would be “getting real community members at the table from the very beginning… so you can obtain really pointed and honest feedback that can help address any roadblocks and mitigate the challenges,” Andrasik says. “It is critical and easy to do but requires relationship-building so [lasting engagement] is not going to be something that happens in the short term.”