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FDA advisory committee debates safety and efficacy standards for a coronavirus vaccine

Outside experts meet for the first time on daunting issues on pandemic vaccines

An FDA advisory panel on Oct. 22 discussed the agency’s standards for a coronavirus vaccine and other issues, including how to keep tabs on the safety of a product once it has been cleared for use. (Dado Ruvic/Reuters)
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Vaccine experts on Thursday rigorously debated the Food and Drug Administration’s planned standards for clearing a coronavirus vaccine quickly for broad use, discussing what level of evidence would be sufficient to establish safety and effectiveness.

The FDA advisory committee, in an all-day virtual meeting, did not consider any specific vaccine. The session served in large part as a venue for the agency to try to reassure the public that any vaccine will be held to a high standard, not the relatively low bar used this year for emergency use authorization for treatments. The FDA said that though it probably will grant emergency use authorizations — which can be handed out faster than full approvals — for the early vaccines, it will use robust criteria similar to those applied in regular approvals.

But committee members, and some individuals during the public hearing part of the meeting, weren’t all convinced. Some questioned whether there should be longer minimum follow-up of people in clinical trials to detect more possible side effects before a vaccine is cleared for broader use. The FDA has said it wants a median of two months follow-up. The panel also debated whether trials that are designed primarily to measure whether vaccines prevent any cases of disease, which could be just mild illness, might result in a product that doesn’t prevent hospitalizations and severe cases.

Some meeting participants also expressed concern that clinical trials might not have enough participants from communities of color — an important issue because those communities have been hit hard by the virus and traditionally have had a higher level of skepticism toward vaccines.

“Since severe disease and death are occurring primarily among minorities with this virus, if we put a vaccine out there that does not address that issue, it’s going to perpetuate the perception that segment of our population does not matter much,” said committee member James E.K. Hildreth Sr., president of Meharry Medical College.

Philip Krause, deputy director of the FDA’s Office of Vaccines Research and Review, responded to questions by saying that a trial designed to prevent severe disease would have to be 10 times as large and would be “unfeasible.” Krause also said that historically, vaccines that are shown to prevent mild disease tend to be more effective against severe disease.

FDA officials said a two-month safety follow-up would pick up most significant vaccine-related side effects while delivering a vaccine without a lengthy delay.

“The criteria we came up with was what we thought was a good balance of what we thought was feasible and what was necessary,” said Doran Fink, deputy director of the Division of Vaccines and Related Products Applications in the FDA’s vaccine office.

The FDA, in its vaccine standards, is requiring that any vaccine be at least 50 percent more effective than placebo and that at least five people in the placebo group develop severe cases of covid-19.

Some panel members were reassured by the FDA’s explanations.

“When people hear the term ‘emergency use authorization,’ what they hear is ‘not necessarily approved or authorized product,’ they hear ‘a permitted product ... a very low bar.’ ... That’s not what we’ve been talking about the last few hours. ... This is much, much closer to what is typically a [full approval] process,” said Paul Offit, an infectious-diseases physician at Children’s Hospital of Philadelphia. “We need to make that clear.”

Officials from government agencies and nonprofit organizations working to address skepticism about vaccines warned that huge challenges loom after clearance of a vaccine, relaying skeptical quotes from listening sessions conducted with Black, Hispanic and Native American communities.

“I firmly believe that this is a Tuskegee experiment,” said one participant in a listening session organized by the Reagan-Udall Foundation, a nonprofit founded by Congress to advance the FDA’s mission. The Tuskegee syphilis experiment was an infamous study in which Black men who had syphilis were not told they had the disease and treatment was withheld from them while researchers watched the progress of the disease.

“Vaccines take years to develop and test. For them to try to do it in a year is pretty absurd,” another participant said.

Committee members also debated whether and how an emergency use authorization could complicate or disrupt clinical trials, including whether people in the placebo group should be given access to the real vaccine. The FDA reiterated Thursday that it wants companies to keep their trials “blinded” even after an authorization, to continue collecting important data. “Once a decision is made to unblind an ongoing placebo-controlled trial, that decision cannot be walked back, and that controlled follow-up is lost forever,” Fink said.

But some vaccine makers, including Pfizer, have said that that position might not be ethical — and that individuals in placebo groups should be notified that a vaccine has been authorized and be allowed to receive the vaccine.

“As an industry, we have an ethical obligation to make our trial participants aware that a vaccine may be available,” the Biotechnology Innovation Organization, which represents biotech companies, said in comments filed to the committee.

The advisory panel, called the Vaccines and Related Biological Products Advisory Committee, is made up mostly of academic experts in infectious diseases, immunology and biostatistics. The FDA has said it will hold additional meetings of the committee to consider applications from vaccine makers, which could begin arriving as soon as mid-November.

The committee meeting was a milestone, especially after protracted political drama involving the vaccine review process, experts said.

President Trump has repeatedly demanded that the FDA clear a vaccine by Election Day. He accused the agency of political gamesmanship when it developed guidance for the pharmaceutical industry on an emergency use authorization that insisted on more safety data — a move that made it almost impossible for any company to have enough information for an approval before the election on Nov. 3. The FDA got around a White House effort to block the guidance by publishing it as part of briefing materials provided to the advisory committee for Thursday’s meeting. The White House subsequently cleared it.

Drug companies, working closely with the U.S. government and fueled by an infusion of more than $10 billion in taxpayer money, have developed a half-dozen vaccine candidates. None has been proved safe and effective. Once a company has gathered what it considers compelling evidence, the FDA review is expected to take a few weeks.

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