Most Americans have never heard of Dr. Richard Whitley, a pediatric infectious disease expert at the University of Alabama-Birmingham.
Still, as the coronavirus pandemic drags on and the public looks forward to a vaccine, it could be among the most powerful people in the country.
Whitley leads a small secret group of experts tasked with reviewing crucial data on the safety and efficacy of coronavirus vaccines that U.S. taxpayers have helped fund, including products from Moderna, AstraZeneca, Johnson & Johnson and others. The Data Monitoring and Safety Board ̵
Protecting the identities of on-board clinicians and statisticians aims to isolate them from pressure from the company sponsoring the process, government officials or the public, according to numerous clinical trial experts who have worked on such commissions. This may be particularly important in the midst of pressure cookers in research into the Covid-19 vaccines, fueled by President Donald Trump’s promises to deliver a vaccine before election day.
As pharmaceutical companies work to produce as quickly as possible, the anonymity of the board has raised concerns that masking the secret could, paradoxically, allow undue influence. Whitley, for example, represents the specialized world inhabited by these experts – a respected professor in academia who is also paid by the pharmaceutical industry.
The lack of transparency is annoying.
Any political pressure to rush pharmaceutical companies or rely on federal regulators to give the vaccine prematurely the green light would undermine the system put in place to ensure public safety. There are growing calls for companies and the government to be more open about who is involved in the review of vaccine trials and whether board members have a conflict of interest.
“We want to know that they are truly independent,” said Dr. Eric Topol, director of the Scripps Research and Translation Institute and a clinical trial specialist. “The lack of transparency is annoying.”
Data and safety monitoring tips have been in place for decades to test new drugs and vaccines, acting as a precaution to ensure that dangerous products do not reach the public. There is usually one board for each product.
This time, a joint DSMB with 10 to 15 experts will review the non-stick data in a number of coronavirus vaccine trials supported by the US government, according to five participants in the Trump administration’s “Warp Speed” operation or another coronavirus vaccine. It is conducted through the National Institute of Allergy and Infectious Diseases at the National Institutes of Health and consists of outside scientists and statistical experts, not federal officials, NIH Director Francis Collins told reporters.
“Until they’re convinced there’s something out there that looks promising, nothing goes blind and isn’t sent to the FDA,” Collins said. “I doubt there have ever been many attempts at vaccines that have been subjected to this amount of testing and the rigor with which it is assessed.”
The NIH Safety Council oversees the trials in the United States by Moderna, Johnson & Johnson and AstraZeneca, said US officials and others involved in Operation Warp Speed, but not Pfizer, which fully funded its clinical trial work and created its own five-member panel for safety . Pfizer has confirmed that it can finalize the effectiveness of its vaccine, developed jointly with German company BioNTech, by the end of October. He secured a $ 1.95 billion purchase agreement with the Ministry of Health and Social Services for the first 100 million doses produced. The agreement allows HHS to purchase an additional 500 million doses.
Moderna, Johnson & Johnson, and AstraZeneca, which have either begun or are about to begin large-scale studies in the United States involving thousands of patients, have received a total of more than $ 2 billion in government funding for vaccine development; billions more have been allocated under agreements similar to the HHS contract with Pfizer for the purchase of millions of doses of vaccine. Having a single safety board to monitor multiple trials could allow researchers to better understand the product area and apply consistency to evaluations, clinical trial experts said in interviews.
One big advantage could be “greater standardization,” said Dr. Walter Orenstein, associate director of the Emory Vaccine Center at Emory University and a former senior official at the Centers for Disease Control and Prevention. “They can look at this data and look at all the tests, instead of doing just one test.”
But it also means that one piece of advice has a huge impact on dictating which coronavirus vaccines will eventually succeed or stop, while most of their identities remain secret. The NIH declined to name them, saying they were “confidential” and could only be identified after a study was completed.
Anonymous for protection against pressure
One exception to the mystery is Whitley, who was appointed chairman by Dr. Anthony Fauci, the largest government official on infectious diseases. Fauci said that after “a combination of information from us and from him and other colleagues, the people who had the most experience in different fields, including statistics, clinical trials, vaccinology, immunology, clinical work,” were selected for the panel .
Whitley’s role went public when the university announced it, an unusual move. He is a professor as well as a board member of Gilead Sciences, who recently signed a contract with Pfizer to produce remdezivir for the treatment of patients with Covid-19. Whitley, who has been on the Gilead board since 2008, conducted a study that led to the development of remdezivir.
In 2019, he was paid about $ 430,000 as a board member of Gilead, according to documents submitted to the Securities and Exchange Commission. That same year, he received more than $ 7,700 in payments from GlaxoSmithKline for consultations, food and travel, according to a federal database that tracks payments by companies for drugs and doctors’ devices.
GlaxoSmithKline and Sanofi are jointly developing a vaccine that received $ 2 billion from the US government as part of Operation Warp Speed. Whitley declined the interview. However, a university spokesman Whitley said his DSMB had not seen any GlaxoSmithKline Covid-19 protocol. The companies have not yet begun phase 3 trials. Although he chairs a separate GSK Data and Safety Safety Board for Pediatric Vaccine, he was screened and authorized by the NIH Conflict of Interest Committee with his knowledge of his involvement, the spokesman said.
“When working responsibly, it’s appropriate for doctors to work with outside organizations,” said UAB spokeswoman Biena Tanical, saying the university works with doctors to ensure industry involvement is appropriate. “This facilitates the critical exchange of knowledge and accelerates and advances in clinical treatments and treatments and nurtures the findings.”
Many experts praised his skills – Dr. Walter Strauss, associate vice president of the pharmaceutical company Merck & Co., said that Whitley is a “high rise” in pediatrics, whom people trust.
“I actually trust this process, and the fact that they asked Rich to do it makes me feel reassured because he’s so good,” said Dr. Jeanne Marazzo, director of the Department of Infectious Diseases at the University of Alabama. Birmingham.
Many scientists who have participated in data and safety monitoring boards say it is important that the board be anonymous to protect them from pressure or even for their safety. For example, when HIV / AIDS testing was conducted in San Francisco, the board was confidential to protect its members from patients desperate for treatment, said Susan Ellenberg, a professor of biostatistics, medical ethics and health policy at the University of Pennsylvania. who writes in detail on the history of the DSMB.
If the patient turns to him, “it would be very difficult for me to tell you, ‘Oh, I can’t help you.’ This is an unreasonable burden, “said Ellenberg, who said she had been involved in coronavirus-related safety boards but would not name them.
As part of a large-scale clinical trial, DSMBs and a statistician or team that prepares data for these individuals are usually the only ones who see non-blind data from the study, making it clear who the treatment is. A firewall has been built between them and executives from the sponsoring company with financial interests in the process. The companies sponsoring the Covid-19 vaccine trials are not part of closed sessions during which non-blind data is reviewed. They are limited to DSMB members, the NIAID executive secretary and the independent non-blind statistician who presents the data, a NIAID spokesman said.
DSMB members or their family members should not have a professional, ownership or financial relationship with sponsoring companies, and the NIAID DSMB executive secretary has checked all members for potential conflicts of interest, NIAID said in response to questions from KHN. Members are paid $ 200 per meeting.
“This is usually done out of a sense of public service,” said Dr. Larry Corey of the Fred Hutchinson Research Center, which works with NIH staff to oversee clinical trials of a coronavirus vaccine in the United States. “You do it because of your sense of altruism and the obligation to know the important role it plays in clinical trials and the important role it plays in preserving the scientific integrity of important experiments.”
Voltage between speed and safety
Moderna, AstraZeneca, Johnson & Johnson and Pfizer have issued protocols that include details of when their DSMBs will review non-binding information about participants in the process and at what points they could recommend a break or suspension of trials. The Vaccine and Safety Data Council, organized by NIAID, advises a broader oversight group consisting of the pharmaceutical companies sponsoring the study and representatives of NIAID and the HHS ‘Biomedical Advanced Research and Development Authority, which reviews the DSMB’s recommendations. Ultimately, the pharmaceutical company has the final authority to provide its data to the Food and Drug Administration.
Moderna and Johnson & Johnson aim for their vaccines to be 60 percent effective, which means there will have to be 60 percent fewer cases of Covid-19 among vaccinated individuals in their trials. AstraZeneca’s target is 50 percent. The FDA says any coronavirus vaccine must be at least 50 percent effective to be approved by regulators. Although the parameters of their clinical trials are similar, there are some differences, including when and how many times the DSMB can perform interim reviews to assess whether each vaccine is working.
Similarly, Pfizer strives to make its vaccine 60% effective. The company allows four interim reviews of data, starting with 32 cases – a schedule that has been criticized by some researchers, who say it makes it easier for the company to stop the process prematurely.
Pfizer declined to name individuals on its monitoring committee, saying only that the group consisted of four people “with extensive experience in childhood and adult infectious diseases and vaccine safety” and one statistician with experience in clinical trials for vaccines. A non-blind team supporting its data monitoring committee – which includes a medical monitor and statistician – will review severe Covid-19 cases upon receipt and any adverse events related to the trial, at least weekly.
“There is an unresolved tension between speed and safety,” said Dr. Gregory Poland, head of the Vaccine Research Group at the Mayo Clinic. “Efficiency is pretty easy to understand. The problem is safety. “