Those concerns come against the backdrop of an accelerating race to develop a coronavirus vaccine as three vaccine makers — pharmaceutical giant Pfizer, biotechnology firm Moderna and drugmaker AstraZeneca — conduct Phase 3 clinical trials, the last before seeking a green light from regulators.
A recent report by Morgan Stanley said the most likely timing for data from one or more of the trials is November. But others say it’s possible some results might be available in October if the vaccines prove spectacularly effective and there are enough viral infections in the community to prove the shots are protecting patients who receive them.
“I think it’s extremely critical that we have rigorous evidence of safety and effectiveness supporting a vaccine before the FDA gives its okay,” said Patricia Zettler, a former FDA associate chief counsel who is a law professor at Ohio State University.
Because vaccines, unlike treatments, are given to healthy people, she and others said, they should be held to a higher standard and go through the full approval process, which can take several months.
In a letter dated Aug. 26, the nation’s infectious-disease doctors demanded that vaccine safety and effectiveness data be “reviewed by internal, as well as independent experts,” if the agency uses an emergency use authorization process.
The FDA’s emergency use authorization is a temporary approval used to accelerate the availability of medical products during a public health emergency. Since February, the FDA used the power to authorize hundreds of coronavirus tests and a few treatments; it has authorized a vaccine that way only once in its history, in 2005, against anthrax. For months, the agency has said it may use the authority for a coronavirus vaccine if it is safe and sufficiently effective.
Amid a pandemic that has already claimed more than 180,000 lives in the United States, some are adamant that emergency use authorization is a lifesaving tool if deployed correctly, since it would be much quicker than the cumbersome full approval process.
Former FDA commissioner Scott Gottlieb said he believes “it is highly likely” the first vaccine or vaccines will be cleared through an emergency use authorization for a select population, such as health-care workers, which he said would be appropriate “as long as the data shows that the vaccine is safe and that it works.”
A number of FDA watchers agree. They say that an emergency use authorization should not be taken off the table but that the agency should spell out more clearly how it might use the procedure for a vaccine, since public trust is critically important and can be easily shaken.
The FDA official in charge of vaccine approvals is attempting to offer those reassurances, saying political considerations will not enter into the process. In an interview Wednesday, Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, which oversees vaccines, said the agency will insist on the same safety and efficacy standards for an authorization as for a full approval.
“Our intention … is not to give the American public anything less than a gold standard,” he said. But he also stressed it would be unethical to insist on all the paperwork typically required for a full application if data showed a vaccine was safe and effective, and people were dying of covid-19, the disease the virus causes.
“We have an obligation to look at that and make a risk-benefit calculation,” he said. “We treat this as though the decisions we are making are decisions we are making for our own families.”
“They could come back before we even have 30,000 folks enrolled and say, ‘We’ve seen enough. This looks great. Pass it on to the FDA,’ ” Paul Mango, deputy chief of staff for policy at the Department of Health and Human Services, said at a Friday briefing for Operation Warp Speed, the administration’s effort to accelerate production of a vaccine.
Under an emergency authorization, Marks acknowledged that follow-up time would be shorter for those in the trials to show possible adverse reactions to the vaccines. He said the agency would require more monitoring after a clearance to compensate.
He also reiterated the agency’s plans to consult its vaccine advisory committee before making a decision. The committee, made up of vaccine and other scientific experts, is scheduled to discuss coronavirus vaccines on Oct. 22. The agenda, as of now, says it will talk about “the development, authorization and/or licensure of vaccines.”
The FDA’s emergency authority dates back 16 years, when a Congress focused on bioterrorism gave the agency the power to greenlight unapproved medical products for life-threatening diseases during a public health emergency when there are no approved alternatives. Since early February, the agency has authorized hundreds of tests, equipment and a few treatments — convalescent plasma being the most recent.
Using that authority, regulators may clear a product once they determine that it “may be effective” and that its “known and potential benefits” outweigh the risks. That is not nearly as tough as the standards for full approval, which require a product be shown to be safe and effective.
Some worry that discretion can be an opening for political pressure. One way to try to avoid any perception of political interference would be for the agency to insist on higher-than-required standards, said Joshua Sharfstein, a former deputy FDA commissioner and now vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Public Health.
Rather than asking the career staff if a vaccine meets the authorization standard, Sharfstein said, scientists should be asked a broader question: “Is this a good idea?”
The FDA’s Marks said the agency already has gone beyond the legal standard of “may be effective” for emergency use authorization by telling vaccine developers that to be cleared either by authorization or full approval, their products must be at least 50 percent more effective than a placebo in preventing covid-19, or in decreasing the disease’s severity.
But vaccine experts worry that any hint of political interference will hurt public trust — with potentially disastrous consequences for the public’s willingness to be immunized.
“If the public doesn’t trust the authorization process and sees it as politically influenced, what is vaccine uptake going to be?”asked John Moore, a virologist at Weill Cornell Medicine.
For all the concerns about potential pre-election interference by Trump, many scientists say a lot has got to happen to get definitive data by October.
Moderna and Pfizer, for example, have enrolled more than half of the 30,000 participants required for each of their trials. But that’s only a first step. Both vaccines require two doses, separated by three to four weeks. It then takes up to two weeks for the immune system to protect against infection, said Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA’s vaccine advisory committee.
Even if both trials complete enrollment by mid-September, it will be more than a month before everyone has received both doses and their immune systems have reacted to the shots. Then, researchers have to wait for people to become infected and count the cases. If a vaccine is 60 percent effective, Fauci has said it may take 160 people to get sick to detect a signal that the vaccine is working. That number might be lower if the vaccine is highly effective.
But if people are not exposed to the virus at high rates, it will take longer to determine whether it works.
Pfizer officials have said repeatedly that they believe they will have data in October that they can present to regulators. Still, Kathrin Jansen, Pfizer’s head of vaccine research and development, said meeting that time frame will depend on how effective the vaccine is and how many people get sick over the next several weeks.
“Everything has to go well, and nothing can get into the way,” Jansen said.
Lena H. Sun contributed to this report.