A small, stealthy panel of experts wields tremendous clout when it comes to selecting which COVID-19 vaccines Americans will ultimately have access to. Part of a working group called the Data and Safety Monitoring Board (DSMB) will help determine which vaccines are ultimately approved by the U.S. Food and Drug Administration (FDA). One of their prominent participants, Dr. Richard Whitley, an expert in pediatric infectious diseases at the University of Alabama-Birmingham, serves on Gilead’s board (maker of remdesivir). While most Americans don’t know Dr. Whitley, he is one of the most influential people in the nation today. TrialSite suggests that a recent piece by Kaiser Health News should be read by those interested in how these vaccines will ultimately get approved. It turns out that the world of drug development can be small, with many overlapping and interlocking ties, interests, and relationships.
DSMB Reviews Clinical-Trial Data
As major pharmaceutical companies and biotech firms drive clinical trials toward the end of Phase 3 clinical trials—often with the help of billions in tax-payer money as part of ‘Operation Warp Speed—firms such as Moderna (mRNA-1273), AstraZeneca (AZD1222), Johnson & Johnson and others face enormous pressure from pandemic conditions, not to mention shareholders and a White House adamant that a vaccine will be ready by the end of the year. The DSMB, as reported recently by Rachana Pradhan with Kaiser Health News, isn’t known by most outside of the drug development industry. A group whose membership is kept secret, such as Dr. Whitley, wields power to shut down an entire study if the data doesn’t look right or give a thumbs up without anyone else even knowing what the data looks like.
Many of the clinicians and statisticians’ identities that participate in the DSMB are kept secret to insulate them from external pressures, such as the sponsoring company or even perhaps government financiers seeking swift approval and/or an aggressive White House. Pradhan commented that at no time has this topic been more relevant, “in the pressure-cooker environment of COVID-19 vaccine research, fueled by President Donald Trump’s promises to deliver a vaccine before Election Day.”
But Could Secrecy Backfire?
Kaiser’s Pradhan suggests, “that the cloak of secrecy could, paradoxically, allow undue influence.” For example, Whitley represents the specialized world these experts inhabit—a professor/academician who is paid by the drug industry, for example. As the pressure builds for a vaccine, the requests grow for industry sponsors and government partners to share who is involved in these committees.
With so much money, political power, and control at stake, is there not some risk for conflict of interest?
The REGN-COV2 Example
TrialSite has reported on the unorthodox start of the Phase 1 clinical trial associated with powerful monoclonal antibody combinations known as REGN-COV2. Produced by innovative biotech Regeneron, the company received $450 million from the U.S. government for the development of COVID-19-focused therapies and rapidly proceeded with multiple clinical trials, including one for those who were in contact with COVID-19 positive housemates and family members. TrialSite asked the question: how could the company launch a major Phase 3 clinical trial in parallel with a preliminary Phase 1 that was just starting? This question was especially relevant as these new advanced monoclonal therapies are novel and powerful. Regeneron’s spokesperson, one of the most open and responsive in the industry, alleviated many of TrialSite’s concerns.
The Regeneron spokesperson reported that the company had established a sentinel cohort (hospitalized and non-hospitalized) that first accessed the drug along with a pre-established arrangement with the FDA. While the data was still blinded in this first-in-human study, the DSMB, based on their interpretation of the data, gave the green light to proceed before the sponsor (Regeneron) could even see the data. But who was behind this mysterious DSMB decision? Were there any members who could possibly be affiliated or associated with the sponsor or the federal government’s Operation Warp Speed? This kind of information isn’t accessible to the public, even though lots of public money is involved. Is there a potential for abuse in such a system? Along with Ms. Pradhan, we believe there is.
Undue Pressure Can Undermine an Entire System
Dr. Erick Topol, director of the Scripps Research Translational Institute, was quoted in Ms. Pradhan’s piece commenting, “We want to know they’re truly independent.” Pressure from a pushy President, pressure-driven pharmaceutical companies, or regulators under the gun to approve a COVID-19 vaccine could undermine public safety. Dr. Topol continued, “The lack of transparency is exasperating.”
Operation Warp Speed’s DSMB
According to Ms. Pradhan, a joint DSMB consisting of 10 to 15 experts has been assembled to review unblinded data across trials for multiple COVID-19 vaccines associated with Operation Warp Speed federal funding. This is the case according to five individuals involved with the Trump administration, Operation Warp Speed, or other vaccine work reports Pradhan. This consolidated DSMB is run and managed by the National Institutes of Allergy and Infectious Diseases at the National Institutes of Health; the group is made up of external scientists as well as statistical experts and no federal employees, reported NIH Director Francis Collins. This group oversees most of the vaccine trials except for the Pfizer/BioNTech trials, which isn’t funded by the feds for development work (although they did secure 100 million doses–along with an option to buy an additional 500 million doses ). Only one of the powerful committee members, with such potential influence, is known to the public.
Disclosure of Whitley
In an unusual move, Professor Whitley’s involvement in the DSMB was disclosed by his employer. Whitley is a board member of Gilead (Remdesivir), which recently signed a contract with Pfizer to make remdesivir to treat COVID-19 patients. Let’s not forget that it was the NIAID (led by Dr. Anthony Fauci) that supported the “changing of the goal posts” during the ACTIV trial, leading to a EUA and up to $1 billion in revenues for Gilead.
A Small and Potentially Incestuous World
The point to Ms. Pradhan’s article is that there is a real potential for a very small and incestuous medical/business ecosystem here. One that is susceptible to bias at best, conflict of interest, or worse. The scientists and statisticians serving on the consolidated DSMB could easily maintain business research ties into the sponsors of the very vaccines themselves decide the fate of. This is not to mention long-standing connections to regulators, NIH researchers, and others in the drug development world. Read the article in its entirety to appreciate just how small this world of drug development can be and the possible risks for conflict of interest, whether intentional and overt or unintentional and indirect.
Call to Action: Read Rachana Pradhan’s “These Secret Safety Panels Will Pick the COVID Vaccine Winners.”