For those closely watching the development of Covid-19 vaccines, Thursday is a crucial date.
Nothing extraordinary is expected to happen when a committee of outside experts — known as the Vaccines and Related Biological Products Advisory Committee, or VRBPAC — meets for the first time to consider Covid-19 vaccines.
But the very convening of the meeting is a reassuring sign that the Food and Drug Administration, which relies on VRBPAC for advice, plans to do what it usually does: Make decisions based not on political timetables but on data that show whether new vaccines are safe and effective.
“It shows the public that this is how FDA is going about its decisions,” said Jason Schwartz, an assistant professor of health policy and management at the Yale School of Public Health.
“It’s not the White House. It’s not the president driving the train, but it’s these processes, these very technical and sometimes dry processes that will be driving the review of vaccines in the months ahead,” said Schwartz, who is not on the committee.
Most federal advisory committees aren’t exactly well known. But VRBPAC — pronounced VER-Pack — may be a bit obscure, even by those standards. So here is some information to keep in mind as the committee holds its first in what will be a string of meetings on Covid-19 vaccines over the next few months.
Who are these folks?
The “A” in VRBPAC is a big clue.
“These are advisers, not deciders,” said Bruce Gellin, president of global immunization at the Sabin Institute. Gellin is a former director of the Department of Health and Human Services’ National Vaccine Program Office.
The 15 or so members of the committee are largely academics and physicians from a variety of specialties useful when one is assessing whether a new vaccine ought to be licensed. There are infectious diseases experts — adult and pediatric — and biostatisticians. People like Paul Offit, a professor of pediatrics and well-known vaccines advocate from the Children’s Hospital of Philadelphia, and Andrea Shane, a pediatrics professor from Emory University School of Medicine.
There is always a representative of the pharmaceutical industry on the panel, but that individual — currently Paula Annunziato, vice president of vaccines clinical research for Merck — cannot cast a vote when the committee is making decisions. There is often a representative of the public on the committee as well.
Conflict of interest rules are strictly applied. Whereas some federal advisory committees only vet experts before they are appointed to serve a term, VRBPAC members undergo conflict of interest vetting before each meeting, said Geeta Swamy, a committee member who must sit out the Covid-19 meetings because Duke University, where she is associate vice president for research, is a clinical trial site for the Pfizer-BioNTech and AstraZeneca vaccines.
Swamy is not alone in having to recuse herself from the Covid-19 VRBPAC discussions. Paul Spearman, of Cincinnati Children’s Hospital — which is also a Covid vaccine clinical trial site — joins her on the sidelines this time, as does the VRBPAC chair, Hana El Sahly, who is an investigator on the Phase 3 trial of Moderna’s Covid-19 vaccines.
The FDA has the capacity to add ad hoc members to VRBPAC to flesh out the ranks when this happens. Documents for Thursday’s meeting that are posted on the FDA website reveal that Arnold Monto, a professor of epidemiology at the University of Michigan, has been named the temporary chairman of VRBPAC. James Hildreth, an immunologist and president of Meharry Medical College, and Jeannette Lee, a biostatistician from the University of Arkansas for Medical Sciences and director of the Statistical Center for the AIDS Malignancies Clinical Trials Consortium, have been added as temporary voting members.
What will VRBPAC do this week? What will VRBPAC do later?
Thursday is the first of what will be a number of meetings for this group on Covid vaccines. “A preview of coming attractions,” said Ruth Karron, who was VRBPAC chair from 2006 to 2008.
Committee members have been preliminarily advised they may have as many as three meetings in November and three in December, Offit said. Those meetings will be called when vaccine manufacturers have enough data from their Phase 3 clinical trials to apply for emergency use authorizations, or EUAs.
In general, VRBPAC meetings serve a couple of purposes, explained Karron, who is the director of the Center for Immunizations Research at Johns Hopkins Bloomberg School of Public Health.
The first is that it gives the FDA a chance to seek guidance from outside experts on specific questions. A possible example: When a vaccine is given an EUA, must the people who were randomized to receive a placebo be informed they didn’t get vaccine, and be offered an opportunity to be vaccinated? Vaccinating them at this early point would limit how much one could learn from comparing the vaccine arm to the placebo arm.
It’s a difficult decision that requires balancing research ethics and the need to gather as much information as possible about these vaccines. “These issues need to be settled,” said Jesse Goodman, a former FDA chief scientist who is currently director of the Center on Medical Product Access, Safety and Stewardship at Georgetown University. “If they don’t, we’re going to end up with a lot of gaps in knowledge.”
Gellin said the committee could also raise its own concerns, or offer thoughts on the FDA’s guidance to manufacturers on what bars their vaccines should meet in order to qualify for an EUA.
The second benefit of the meeting is that it allows the public to raise concerns, Karron said. VRBPAC meetings are always open and members of the public have the right to ask to address the committee. (If there are more requests than time limits allow, public comment slots are allocated by lottery.)
Karron called the meetings “a two-way street.”
When VRBPAC eventually makes recommendations, will the FDA embrace them?
The regulatory agency is not obliged to follow the advice of its advisers. But it often does.
Offit and others point to the last time VRBPAC met to discuss a completely new vaccine — when the FDA asked its advice on Sanofi’s troubled dengue vaccine, Dengvaxia.
The world badly needs effective dengue vaccines. But it had become clear the Sanofi product could only be safely used in people who had already had at least one previous dengue infection. Dengue can sometimes cause life-threatening and even fatal infections; that most often happens during a person’s second bout of the disease. It was feared — and later seen to be true — that people who had never had dengue before being vaccinated were at higher risk of serious illness if they later contracted the disease.
VRBPAC members expressed serious concerns about the vaccine, recommending it only be licensed for people aged 9 to 16, and even then, only those who had had one previous infection and who lived in a part of the United States where dengue is endemic. That means only Puerto Rico and a few other offshore territories and protectorates — a tiny potential market.
Sanofi had asked that the vaccine be authorized for use in people aged 9 to 45. The FDA accepted the advisory committee’s when it approved Dengvaxia two months later.
If VRBPAC is part of normal vaccine approval, why are experts so happy it is meeting about Covid-19 vaccines?
For months public health and vaccine experts have worried that President Trump, in a bid to bolster his chances of re-election, would force the FDA to authorize Covid-19 vaccines before they were shown to be adequately safe and effective. Offit and Ezekiel Emanuel, an ethics expert from the University of Pennsylvania, warned of this possibility in a New York Times op-ed in early June. (Emanuel is also an adviser to Democratic presidential candidate Joe Biden.)
Trump let is be widely known that he wanted a vaccine before Election Day. But Peter Marks, who heads FDA’s Center for Biologics Evaluation and Research, and Moncef Slaoui, co-chair of Operation Warp Speed, the government’s effort to fast-track Covid vaccines, drugs and diagnostics, have both publicly declared they would quit if Trump forces the agency to approve vaccines without adequate evidence of safety and efficacy.
As the politicization of Covid vaccines has heated up, the public’s interest in the vaccines has cooled. A series of polls — including one published Monday by STAT and The Harris Poll — show the number of people who say they are willing to accept a Covid vaccine is declining, even as infection rates in the country surge. Several states have indicated they will not recommend vaccination on the federal government’s say so alone. New York’s Andrew Cuomo has set up his own expert group to weigh in on the vaccines as they become available.
Experts see VRBPAC as a buffer, a way of assuring the public that vaccines fast-tracked with the help of Operation Warp Speed are being evaluated with the same rigor as any other vaccine.
Offit said he feels no political pressure. “We are independent,” he said.
Cody Meissner, director of pediatric infectious diseases at Tufts University School of Medicine, doesn’t feel political pressure either — but knows the optics around Covid vaccine approvals are enormously important to their acceptance and use.
“We’re going to get one chance to introduce a vaccine,” Meissner said. “And if that goes badly, it’s going to be a long time before we get another Covid-19 vaccine.”
Excellent article. This VRBPAC will restore and respect long-missing trust in the system. Eliminating politics AND possible conflicts-of-interest almost guarantees unbiased study of vaccine candidates and delivery of reliable recommendations to the FDA. It’s about time !
Get it right! Cut the throat of politics!
Do we know if the effectiveness data will be made public? Will we get to see the numbers in each category, for each vaccine and placebo: number uninfected/infected (asymptomatic/mild/moderate/severe/death)?
I have two questions hopefully would be answered in some manner. What is the rationale for holding up Astra Zeneca’s vaccine trial in the US when trials in other nations such as the UK is allowed to conti us?
What is the precise role of Dr. Anthiny Fauci during the vaccine approval process.
1. Only FDA knows. Different regulatory bodies often look at the same data and make different decisions (e.g. most famous example is thalidomide, approved only Europe and not in the US).
2. Fauci is NIH. He will have no formal at FDA in approving or not approving.
He may speak at an FDA panel, but he won’t have a vote and most certainly won’t contribute to Internal FDA debate.
I’d be interested in knowing whether this committee will consider the recent report from the National Academies entitled “Equitable Allocation of COVID vaccine,” especially since the NIH and the CDC commissioned that report and it was written and researched by a similar panel of experts. Are these two related? Could you write about whether this report will inform this new committee’s work?
This committee will likely not be tasked with that at all. FDA decides to approve or not and write a very specific “label” for a new product.
Allocation and Distribution is outside its purview.
Each state has the right to allocate the vaccine as it wishes. All states (and territories and five large cities) filed a plan last Friday with the CDC as to how they will allocate the vaccine. I imagine the CDC will apply the principles of that report in working with the states on their plans, and in allocating the vaccine among the states.
The VRBPAC committee is not a new committee, but it will be considering the Covid-19 vaccines for the first time.
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