Clinical Trial Diversity Requires Community-Based Research Infrastructure, US FDA’s Woodcock Says
Executive Summary
COVID-19 trials could have reached underserved populations better if research infrastructure was in place where people routinely get their health care, acting commissioner Janet Woodcock says; PhRMA is looking to establish a public-private partnership that would build a sustainable community-based infrastructure for clinical research.
The COVID-19 pandemic has highlighted the need to build clinical research infrastructure in community settings to ensure speedy trial enrollment and adequate representation of diverse populations.
Expansion of the research enterprise beyond academic medical centers could get a big boost from the creation of a public-private partnership focused on this objective and by designing simple, pragmatic trials that can be readily conducted in communities, government and industry representatives said during a 10 March webinar sponsored by the Milken Institute.
Reflecting on lessons learned from the pandemic, leaders from the US Food and Drug Administration, National Institutes of Health, biopharma industry and advocacy community recounted the push to try to enroll diverse populations in trials for COVID-19 vaccines and therapeutics, reasons why those efforts were not always successful in the current clinical research structure, and how to head off such problems in advance of the next public health crisis.
“If we don’t have research infrastructure in the community where people get their health care, where they are used to going, then we’re not going to reach those communities in an emergency because you cannot just build up infrastructure capacity in the middle of a pandemic.” – FDA’s Janet Woodcock
“If we don’t have research infrastructure in the community where people get their health care, where they are used to going, then we’re not going to reach those communities in an emergency because you cannot just build up infrastructure capacity in the middle of a pandemic,” FDA acting commissioner Janet Woodcock said.
“One of the reasons we could not reach those populations as well as everyone desired is they didn’t have the clinical trials infrastructure support, the research personnel. The investigators didn’t have training. They hadn’t been doing research because they hadn’t been supported in doing research,” Woodcock said. “We have to move clinical research out into the community, and we have to support that if we’re going to be successful in any way in enrolling populations who reflect this country.”
‘Galvanized’ Industry Eyes Public-Private Partnership
While the notion of bringing clinical trials to patients – rather than the other way around – is not new, it has taken on a new urgency with COVID-19, which has had a disproportionate impact on morbidity and mortality in traditionally under-represented communities.
Biopharma companies are re-examining their inclusion and exclusion criteria with an eye toward boosting study diversity, and have increased the attention paid to recruiting more representative populations.
(Also see "Clinical Trial Diversity: We Must ‘Turn This Moment Into A Movement’" - Pink Sheet, 18 Feb, 2021.)
Nevertheless, it became apparent early in the pandemic that even with industry efforts over many years to diversify clinical trial enrollment, reaching those in underserved communities was still a struggle, said Richard Moscicki, chief medical officer and executive VP-science and regulatory advocacy at the Pharmaceutical Research and Manufacturers of America.
“I think on that front industry itself has really been galvanized in a way that it never had before in this past year,” Moscicki said.
“We’re quite committed this year to trying to find the right way to launch a public-private partnership that will … build a sustainable community-based infrastructure for clinical research.” – PhRMA’s Richard Moscicki
He noted that all PhRMA member companies have signed on to the trade association’s new principles for enhancing diversity in clinical trial participation.
Those principles, released in November, call for making clinical trial participation less burdensome through the use of digital data collection tools, recruiting clinical trial personnel with diverse backgrounds, and getting patients, caregivers and investigators from underserved communities more involved in the trial design process. (Also see "Reducing Clinical Trial Burdens Brings Greater Participant Diversity – PhRMA" - Pink Sheet, 17 Nov, 2020.)
However, PhRMA is looking to do more.
“We’re quite committed this year to trying to find the right way to launch a public-private partnership that will … build a sustainable community-based infrastructure for clinical research,” Moscicki said.
"Our goal with this public-private partnership is to create a community-based network of centers focused on enhancing diversity in clinical trials," PhRMA told the Pink Sheet. "This is something we are absolutely committed to tackling this year along with other interested stakeholders, including members of our industry, key government entities and community partners."
Woodcock welcomed the idea of a public-private partnership. “I believe both government and industry need to ban together, and maybe a PPP is the way to do it and provide sustainable trial personnel and training to investigators who are in the community,” she said.
In the current pandemic, the lack of trained investigators in community settings has not just been a problem for those communities that have been historically underserved, she said.
“We had tens of thousands of people dying from COVID and we couldn’t get patients enrolled because we didn’t have enough sites, and even if the major medical center had a site going their network sites out in the community didn’t have trained personnel,” Woodcock said. “This is not something … you can do on a dime. You have to build a sustainable infrastructure.”
Simplifying Studies ...
In addition to building infrastructure, designing trials that can be readily conducted in community settings is critical to expanding the reach of clinical research.
“Simplifying trials would really help,” Woodcock said.
Pragmatic community-based trials are ideal for answering questions about provision of health care and what kind of treatment policy should be used for a given disease, she said. “They could be used also for a pivotal trial, or a portion of the pivotal trials, for investigational drugs and devices, but they have to be simple enough.”
“Not that I’m saying the community researchers are going to be simplistic,” Woodcock continued. “They just won’t have time and they won’t have the extensive laboratory backup and all that sort of stuff that people at the medical centers do.”
The FDA is working with a variety of partners to try to run studies off of information routinely entered in electronic health records, rather than having separate case report forms, she said. “This simplifies and enables other parties involved mainly in clinical care to participate. But these trials have to be more pragmatic. We can’t have dozens of researchy-type of activities associated with them.”
Yet, even these simpler studies require a certain amount of infrastructure and training. Consequently, the goal is to set up pragmatic trials and infrastructure support to enable the participation of community practitioners, Woodcock said. “The question is where can the funding come from that would support this kind of ongoing activity?”
... And Engaging With The Community
NIH director Francis Collins highlighted the need for community engagement in the trial design and recruitment process, pointing to the large Phase III studies of the COVID-19 vaccine candidates as a useful case study.
The FDA’s June 2020 guidance on COVID-19 vaccine development strongly encouraged enrollment of populations most affected by the disease, specifically racial and ethnic minorities. The FDA also said evaluation of vaccine safety and efficacy in late-stage trials should include adequate representation of elderly individuals and individuals with medical comorbidities.
Vaccine sponsors were vocal about their commitment to enroll diverse populations in the Phase III studies, and Pfizer Inc. and Moderna, Inc. even posted regular updates on the diversity of their subjects while the trials were enrolling. (Also see "Pfizer COVID-19 Vaccine Trial Diversity Slips As Enrollment Rises, Unlike Moderna" - Pink Sheet, 18 Sep, 2020.) Pfizer expanded its Phase II/III trial target enrollment from 30,000 to 44,000 in a bid to increase diversity and include adolescents and immunocompromised individuals.
“I can’t tell you how many Saturday mornings I spent … meeting with the leadership of the companies that were running those trials, trying to do what we could to boost up the participation of diverse individuals, because it was not going well at the beginning for most of these.” – NIH’s Francis Collins
Among the first four fully enrolled Phase III vaccine studies designed to support emergency authorization in the US, enrollment of Black and Hispanic participants ranged from 10%-19% and 11%-45%, respectively, with approximately one-quarter to more than one-third of participants falling into the older age groups. (Also see "COVID Trial Diversity: What Participants In The Vaccine Phase III Studies Look Like" - Pink Sheet, 8 Feb, 2021.)
Collins said the diversity achieved in the Phase III studies was the result of a lot of hard work and community engagement.
“I can’t tell you how many Saturday mornings I spent – probably at least 15 or 16 of them – meeting with the leadership of the companies that were running those trials, trying to do what we could to boost up the participation of diverse individuals, because it was not going well at the beginning for most of these,” Collins said.
“It took a very specific commitment at the top level of all those organizations, and a willingness to spend more money and perhaps even slow down a little bit in terms of the … timetables that we were trying to meet, in order to end up with trials that actually looked like the country,” he said. “So people could look at the trial and say, ‘I see myself in there, I see people like me benefitted from this vaccine as well.'”
He credited some of this success in enrolling diverse populations to establishment of the Community Engagement Alliance. CEAL’s mission is to provide trustworthy information through active community engagement and outreach to people in communities hardest hit by the pandemic – including African Americans, Hispanics/Latinos and American Indians/Alaska Natives – with the goal of building long-lasting partnerships and improving diversity and inclusion in the NIH’s COVID-19 research response, according to the alliance’s website.
“You’ve got to have the infrastructure for that kind of community engagement at the start,” Collins said. “You don’t build that on the fly, at least it’s not going to work very well. You have to invest in that. We have to remember that lesson going forward, not just for the next pandemic but for everything we do.”
Collins and Woodcock also discussed another lesson learned from the pandemic - the need for a coordinated approach to clinical research.