TrialSite has reported that the COVID-19 Prevention Network, a reorganized and merged group of National Institutes of Health (NIH) infectious disease-focused trial site networks, sincerely emphasizes the participation of demographic groups hardest hit by COVID-19 including the elderly, essential workers as well as People of Color, which represent approximately 120 million people in the United States. NIH and its infectious disease organization, the National Institute of Allergy and Infectious Diseases (NIAID), have been adamant that COVID-19 clinical trials diversify so that those at risk are truly represented. Dr. Anthony Fauci, having worked on HIV/AIDS research and development decades ago, experienced first hand the devastation that virus had on minority communities, especially certain segments of the African American population. However, despite all of the awareness and proclamations of ACTIV, the very group organized by Fauci and company to organize and coordinate all major COVID-19 trials—at least those that are part of Operation Warp Speed—includes out of 116 participants not one participant purely out of health systems or community health; moreover, only 3% of those participating in the core decisions are African American or Latinx. That lack of diversity at the decision-making table manifest and influence actual design of the studies and the participation results, as CNBC recently surveyed some of the first vaccine studies and finds the problem of lack of participation by People of Color persists.
As some of the TrialSite principals have been involved with clinical trials patient recruitment for a couple decades, it becomes apparent that the exact same problems and issues that were relevant in the year 2000 persist in 2020. CNBC’s Meg Tirrell, Berkeley Lovelace, Jr. and Harriet Taylor do a great job probing this topic involving some of current COVID-19 vaccine trials, including Moderna and Pfizer. The TrialSite strongly recommends readers to visit this CNBC article.
The journalists quote Michele Andrasik, a professor with the University of Washington and director of community engagement for COVID-19 Prevention Network, who conveyed to the CNBC journalists, “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.” Of course, CNBC reminds that because “Racial and ethnic minorities are not only getting COVID-19 at higher rates but are also having worse outcomes, studies have shown.”
Ms. Andrasik suggests that the COVID-19 Prevention Network will leverage past lessons learned and best practices associated with HIV research due to “vast” similarities with COVID-19.
CNBC interviewed Thomas Silvera, a patient advocate and President and CEO of the Elijah-Alavi Foundation (a non-profit dedicated to helping children). Mr. Silvera communicated what most already know in the clinical trials business: that People of Color, particularly African Americans and also Latinos, are leery of participating in human clinical trials due to a plethora of historical and present day factors. To understand more, see the TrialSite News survey of African Americans and disparity in health and clinical research.
And as People of Color are left out of critical studies, fundamental gaps are introduced. For example, CNBC includes the recent dexamethasone breakthrough out of University of Oxford RECOVERY trial, showcasing that the common steroid used as an anti-inflammatory can help reduce death rates among certain segments with severe to critical COVID-19. However, the CNBC team point to comments by to Namandje Bumpus, a Johns Hopkins Medicine pharmacologist, who points out that dexamethasone may works differently in Black people, and if the clinical trials don’t include sufficient African Americans, for example, the results may showcase a benefit to the White population but could actually end up detrimental to the Black population. Is that fair, or right?
Moving Forward with Pivotal Phase 3 Vaccine Trials
Although the Phase 1 trials were not sufficiently diversified, CNBC reports that that wasn’t the goal as NIAID reported, “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 particular sites and who met the trial’s inclusion criteria.” However, CNBC suggest that diversity of participation is high on the minds of trial teams involved with the Moderna Phase 3 pivotal trial, to include 30,000 participants. Ditto for the late stage Pfizer and BioNTech trials testing BNT162, the mRNA-based vaccine program developed in Germany.
The CNBC team refer to the challenge identified by Dr. Tal Zaks, Chief Medical Officer for Moderna, who during a New York Academy of Sciences panel discussion emphasized the challenge of recruiting minority participation. Its almost a luxury to participate in a clinical trial: one must have the time, the means, the ability to let other commitments go, and in so-called underrepresented populations, where incomes may be lower and time for anything other than working to support family is what matters. Moderna is taking diversity for the mRNA-1273 Phase 3 trial seriously as Zaks told the CNBC journalist that he will personally monitor the diversity associated with the trial participation and the trial operation “will preferentially enroll at places that are able to reach out to those populations.”
Meanwhile Linda Goler Blount with the Black Women’s Health Imperative rightly connects inclusion of Black women, for example, with upfront planning, which would require contemplation at the protocol level during trial design. CNBC quotes Ms. Blount, “The No.1 reason Black and Brown people don’t participate in clinical trials is because nobody asks them.”
CNBC highlights a novel approach led by Dr. Richard Novak, the lead investigator of the Moderna vaccine trial at the University of Illinois at Chicago. By using a mobile clinic, the Chicago team will undertake outreach to African-American demographic via churches, warehouses and other places where large outbreaks have occurred.
Good News…But where’s the Data?
Back to Ms. Andrasik, again who represents the COVID-19 Prevention Network’s imperative to diversify the pivotal late-stage trials. She reports great news to the CNBC team: that since they have gone live with the network’s website on July 8, over 150,000 people have signed up to volunteer in the vaccine trials. Truly an impressive number, and the TrialSite applauds this work.
However, Ms. Andrasik, when questioned by the CNBC journalists about how many of the 150,000 were People of Color, couldn’t answer the question. Rather she was quoted by the CNBC team, “People have to feel that this is something that is good for them and their community.” And, of course, this leads to the next standard line: We must build more trust “and that doesn’t happen overnight.” Yes, with the same model in place, it will be a long time and a lot of public money spent.
But it is certainly very easy with any structured data base, or for that matter a Microsoft Excel spreadsheet, to analyze 150,000 data points. This is very basic stuff. Why can’t the COVID-19 Protection Network simply analyze the 150,000 volunteers to determine the racial and ethnic breakdown, unless A) there isn’t the competency to do so (which clearly isn’t the case) or B) the numbers don’t look too good.
Given the unprecedented amount of public money pouring out of Operation Warp Speed we expect better answers. America’s 120+ million People of Color need to be represented, and this will take not just a model represented by top-down trust building but a complete shake up of how clinical research is conducted and governed. And this applies to other underrepresented groups that include millions of Whites who are disproportionately hit by this pathogen. The elderly population has been devastated and the TrialSite has grave concern about how this critically important population will be cared for and represented in the vaccine process.
Back to the Leadership of ACTIV
The TrialSite is independent and thus can and will take what can be deemed unpopular stances by those in seats of power. The National institutes of Health (NIH) launched the ACTIV public-private partnership in April to develop a coordinating research strategy for prioritizing and speeding development of the most promising treatments and vaccines. They hand selected an impressive group of brilliant people in a well-intentioned bid to help the country (and elsewhere) combat this pandemic.
However, an underlying assumption of ACTIV as manifested in its leadership, whether intentional or not, centers on a core principal that gold-standard research is first and foremost separate from the clinic in the community. The elite of research from the federal government, Pharma and some academic medical centers will lead and direct policy as well as serve as a stage gate to determine even what research receives federal dollars, which clearly impacts on-the-ground planning. In the meantime, the clinic can wait for the evidence from such effort.
The whole affair is built on the false premise that structured, gold-standard research comes first in this modern, data-rich world despite pervasive and powerful real-world, real-time evidence. Of course, research and Real-World must evolve and synthesize as they complement each other as highlighted by the FDA. Change in outcomes often requires a critical review of the root causes behind a problem. The TrialSite has already profiled the ACTIV leadership as at least one indication: although the overwhelmingly leadership truly is exceptional, brilliant and well-intentioned, by not including at the leadership table in all “Fast Track” areas a healthy and robust mix representing a diversity of experience (including many from the clinic) and of background (only 3% African American and Latinx), it won’t truly be able to effectuate the change it seeks.
The TrialSite will monitor this group for additions to leadership, which is fully expected.