These secret safety panels choose the winner of the COVID vaccine

Reviewed by Emily Henderson, B.Sc.September 24, 2020

Most Americans have never heard of Dr. Richard Whitley, a pediatric infectious disease expert at the University of Alabama at Birmingham.

Still, he may be among the most powerful people in the country as the coronavirus pandemic progresses and the public awaits the vaccine.

Whitley leads a small secret panel of experts reviewing important data on the safety and efficacy of coronavirus vaccines funded by US taxpayers, including products such as Moderna, AstraZeneca, Johnson & Johnson. The data and safety monitoring board, known as DSMB, is used to ensure that the drug is safe and functional. It has the power to discontinue a clinical trial or track it quickly.

According to multiple clinical trial experts who participated in the committee, protecting the identities of the committee’s clinicians and statisticians protects them from pressure from the companies, government officials, or the public that sponsor the trial. Means. This could be especially important in the pressure cooker environment for COVID vaccine research, supported by President Donald Trump’s promise to provide vaccines before election day.

The anonymity of the board raises concerns, secretly and paradoxically, that it can have an undue impact, as pharmaceutical companies strive to manufacture as quickly as possible. Whitley, for example, represents the professional world inhabited by these professionals. This is an academia-respected professor who is also paid by the pharmaceutical industry.

Political pressure to rush to pharmaceutical companies or rely on federal regulators to authorize vaccines prematurely undermines the systems introduced to ensure public safety. There is a growing call on companies and governments to be more open about who is involved in vaccine trial reviews and whether board members have conflicts of interest.

“I want to know that they are really independent,” said Dr. Eric Topol, director of the Scripps Research Translational Institute and clinical trial specialist. “The lack of transparency is frustrating.”

Data and safety oversight committees have existed for decades to scrutinize new drugs and vaccines and act as a backstop to keep dangerous products out of the public. There is usually one board for each product. According to five people involved in the Trump administration’s Warpspeed operation and research on other coronavirus vaccines, this time the joint DSMB with 10 to 15 experts is a multiple coronavirus funded by the U.S. government. Review open-label data for the entire vaccine trial. NIH Director Francis Collins called a reporter, which runs through the National Institutes of Health’s National Institute of Allergy and Infectious Diseases and consists of outside scientists and statistical experts rather than federal staff. Said.

“Nothing is blind and will not be sent to the FDA until they are convinced that there is something that looks promising,” Collins said. “It is doubtful that there have been so many vaccine trials of this scale and the rigor in which they are being evaluated.”

The NIH Safety Commission oversees clinical trials in the United States from Moderna, Johnson & Johnson, and AstraZeneca, and Pfizer is sufficient for clinical trial work, including U.S. military personnel and others involved in the operation of Warp Speed. Established a unique safety panel for 5 people. Pfizer has proven that the efficacy of the vaccine, co-developed with the German company BioNTech, can be decisively determined by late October. We have signed a $ 1.95 billion purchase agreement with the Department of Health and Human Services for the first 100 million doses produced. The agreement allows HHS to choose to purchase 500 million additional purchases.

Moderna, Johnson & Johnson, and AstraZeneca have launched or are aiming to launch a large-scale trial in the United States with thousands of patients, totaling more than $ 2 billion for vaccine development. I received the funds. Billions more are being filled under a contract similar to the HHS contract with Pfizer to buy millions of vaccines. As clinical trial experts said in an interview, one safety committee oversees multiple trials, allowing researchers to better understand the area of ​​the product and apply consistency throughout the assessment. I can do it.

One major advantage would be “more standardization,” said Dr. Walter Orenstein, deputy 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 that data and see all the exams, not just one.”

But it also has an oversized influence by one committee to determine which coronavirus vaccine will eventually succeed or stop, while most of its coronavirus identity remains secret. It also means that you have. NIH did not reveal their names, stating that they were “confidential information” and could only be identified after the investigation was completed.

One exception to this mystery is Whitley, chaired by Dr. Anthony Fauci, a top US infectious disease expert. Fauci said, “People with the greatest expertise in various fields such as statistics, clinical trials, vaccination, immunology, clinical research, etc. after combining information from us and him and other colleagues” will be on the panel. Said he was chosen.

Whitley’s role was revealed when his college announced it. He is a professor of Gilead science and a member of the board. Contract With Pfizer, which manufactures remdesivir for the treatment of COVID-19 patients. Whitley, who has been a board member of Gilead since 2008, conducted research that led to the development of Remdesivir.

According to a document submitted to the Securities and Exchange Commission, in 2019, about $ 430,000 was paid as a director of Gilliad. That same year, he received over $ 7,700 in payments from GlaxoSmithKline for consulting, dining and travel. Federal database Track drug and device company payments to your doctor.

GlaxoSmithKline and Sanofi are jointly developing a vaccine that received $ 2 billion from the US government in Operation Warpspeed. However, Whitley told a university spokeswoman that his DSMB had never seen the GlaxoSmithKline COVID protocol. Both companies have not yet started Phase 3 trials. A spokesperson said he chaired the individual GSK data and safety oversight committee for pediatric vaccines, which was reviewed and approved by the NIH Conflict of Interest Committee.

UAB spokeswoman Beena Thannickal said, “If treated responsibly, it is appropriate for doctors to work with external organizations to ensure proper collaboration with the industry.” He said he was working with a doctor. “It facilitates the exchange of important knowledge, accelerates and advances clinical treatment and treatment, and facilitates discovery.”

Several experts praised his skills — Dr. Walter Strauss, Associate Vice President of the pharmaceutical company Merck & Co., said Whitley is a “outstanding rise” in pediatrics that people trust.

Dr. Jeanne Marazzo, Head of Infectious Diseases, University of Alabama and University of Birmingham, said:

Scientists who participated in the Data and Safety Oversight Committee argue that it is important to keep the committee anonymous in order to protect them for pressure or their safety. For example, when a trial for an HIV / AIDS study was conducted in San Francisco, the board was confidential to protect members from patients desperate for treatment and biostatistics, medical ethics and health at the University of Pennsylvania. A professor of policy, extensive on the history of DSMB.

As the patient approaches, it will be very difficult to say, “Oh, I can’t help you.” That’s an unreasonable burden. “

Statisticians or teams that prepare data for DSMBs and their individuals as part of a large clinical trial are generally the only ones to see open-label data about the trial, who and which treatment. Clarify if you are receiving. A firewall has been set up between them and the executives of the sponsoring companies that have a financial interest in the trial. The companies sponsoring the COVID vaccine trial are not part of a closed session where unblind data is being reviewed. According to a NIAID spokesperson, these are limited to DSMB members, the NIAID Executive Secretary, and independent, open-label statisticians presenting the data.

In response to questions from KHN, NIAID needs to ensure that DSMB members or their families do not have a professional, property, or financial relationship with the sponsoring company, and NIAID DSMB Executive Secretary has potential. All members were scrutinized for conflicts of interest. Members are paid $ 200 per meeting.

“It’s generally done from a public service perspective,” said Dr. Larry Collie of the Fred Hutchinson Cancer Research Center, who is working with NIH officials to oversee US coronavirus vaccine clinical trials. “You do it because you have a duty to know the sense of altruism and the important role it plays in clinical research and the important role it plays in maintaining the scientific integrity of important trials. “

Moderna, AstraZeneca, Johnson & Johnson, and Pfizer each release protocols that include details on when DSMB reviews open-label information about study participants and when it is recommended to suspend or discontinue the study. Did. The NIAID-sponsored Vaccine Data and Safety Committee advises a broader monitoring group of pharmaceutical companies sponsoring clinical trials, NIAID representatives, and HHS’s Advanced Biomedical Research and Development Department to review DSMB recommendations. .. Ultimately, the pharmaceutical company has ultimate authority over whether to submit the data to the Food and Drug Administration.

Moderna and Johnson & Johnson are each aiming for a 60% vaccine efficacyThis means that their trials will require a 60% reduction in COVID cases in vaccinated individuals. AstraZeneca’s goal is 50%. The FDA states that the coronavirus vaccine must be at least 50% effective in order to be approved by the regulator. Although the parameters of clinical trials are similar, there are some differences, such as when and how many interim reviews can be performed by DSMB to assess whether each vaccine works.

Pfizer is also aiming for a 60% vaccine effectiveness. The company allows four interim reviews of data starting at 32 cases. The schedule has been criticized by some researchers who claim that this will make it easier for the company to stop the trial early.

Pfizer refused to reveal the names of its members of the monitoring committee, with the group having four “experienced in pediatric and adult infections and vaccine safety” and experience in vaccine clinical trials 1 He said it was made up of human statisticians. An unblind team supporting a data monitoring committee, including medical monitors and statisticians, receives severe cases of COVID-19 and reviews study-related adverse events at least once a week.

Dr. Gregory Poland, Head of the Mayo Clinic Vaccine Research Group, said: “The effect is easy to understand. Safety is an issue.”

Arthur Allen, Editor of California Healthline, contributed to this report.