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There are serious signs the Food and Drug Administration is getting cold feet over the notion of issuing emergency use authorizations to allow for the widespread early deployment of Covid-19 vaccines.

Instead, it appears the agency may be exploring the idea of using expanded access — a more limited program that is typically used for investigational drugs — in the early days of Covid vaccine rollouts.

Whereas a few weeks ago the agency’s concern was to protect against the possibility that unproven vaccines would be pushed out prematurely due to pressure from President Trump, now the fear is that early authorization of vaccines could squander a one-time chance to determine how well the various vaccines work and which work best in whom.

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Marion Gruber, director of the FDA’s office of vaccines research and review, put the issue on the table when members of the Vaccines and Related Biological Products Advisory Committee began to discuss a series of questions FDA staff posed at the end of a grueling day-long virtual meeting Thursday.

“We are concerned about the risk that use of a vaccine under an EUA would interfere with long-term assessment of safety and efficacy in ongoing trials and potentially even jeopardize product approval,” Gruber said. “And not only the first vaccine, but maybe even follow-on vaccines.”

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The acting chair of the committee, Arnold Monto, from the University of Michigan, who has decades of experience studying the efficacy of vaccines, put it in more dire terms during the discussion. The maker of a Covid-19 vaccine that is given an EUA might not be able to generate enough additional data to ever successfully apply for a full license, Monto said.

The problem stems from thorny ethical questions about whether — once a vaccine has been cleared for use by the FDA — the people who were randomly assigned to receive a placebo in its clinical trial must be informed and offered vaccine. Vaccinating the people who received placebo injections — the trial’s control arm — would end the ability to continue to compare the two groups after what would have been a short trial.

Pfizer and BioNTech, the collaboration expected to be first to apply for an emergency use authorization — sometime in mid-November — have indicated they plan to unblind their trial and offer people in the placebo arm vaccine. (When a trial is blinded, participants don’t know if they received vaccine or a placebo injection.)

Early unblinding of these trials actually runs counter to the FDA’s advice. The agency is urging vaccine manufacturers to keep their trials blinded as long as possible, to collect as much data as they can.

The EUA could trigger another related problem. People in clinical trials might choose to pull out and try to get the vaccine that has been authorized for emergency use, especially if they are in a high-risk group that is likely going to be at the front of the line when vaccines begin to become available. Enrollment in the vaccine trials for other Covid vaccines might slow as people decide they don’t want to risk being randomized to receive a placebo, and instead wait for their turn to get vaccine cleared under an EUA.

If they are stopped too early, the trials, which were structured to come up with quick answers as to whether Covid vaccines prevent symptomatic Covid-19 infections, might fail to answer additional, important questions needed to figure how to best use the various vaccines that have been produced, if — as expected — multiple vaccines prove to work.

For most of the vaccine trials, the “primary endpoint” is showing they prevent symptomatic Covid-19 disease in at least 50% of vaccinees. But there are also “secondary endpoints.” Secondary endpoints include whether the vaccines reduce the number of severe Covid cases, and how well they work in important subsets of the population such as the elderly or people of color, who have been disproportionally hit by the pandemic. Trials that end after reaching their primary endpoint will leave gaping knowledge gaps, a number of experts warned.

“We may have limited and in some instances no information about some of the secondary endpoints,” said Stephanie Schrag, an epidemiologist from the Centers for Disease Control and Prevention who made a presentation at the meeting. “This would be particularly true in the instance of an early EUA because many of these secondary endpoints require longer time than the primary to accrue events.’’

Jesse Goodman, a former FDA chief scientist who listened to the meeting, concurs with the agency’s concerns. Answers about how well these vaccines work, how long they work, and which work best for which segment of the population will always be clearer if they are generated by randomized controlled trials — the gold standard of clinical trials.

“Let’s say one of these vaccines has, you know, 60% efficacy and another one has 80%. Or one of them, the efficacy waned after four months, and the other lasts a last year. It’s going to benefit people to find that out now rather than three years later from crummy observational data,” Goodman told STAT.

Using expanded access rather than emergency use authorizations would be a more cumbersome process and create some challenges. People who were to be vaccinated would have to sign informed consent forms, which requires a discussion of risks and benefits during vaccine administration; safety data from vaccinees also would have to be gathered. But Goodman, who actually suggested expanded access as an option in a commentary he co-wrote in JAMA in July, said that this route might better ensure the continuation of the clinical trials.

Members of FDA’s advisory committee appeared to share the concerns of the agency staff who were asking for their guidance.

Sheldon Toubman, a lawyer from New Haven, Conn., who is the consumer representative on the panel, said it would be his preference that the vaccines not be deployed under emergency use authorizations. Toubman said the public fears politics, not science, is driving the approvals process and EUAs won’t dispel those views.

A number of polls, including one published Monday by STAT and the Harris Poll, have shown that the public is cooling to the idea of Covid vaccines. The declining percentage of Americans who say they are willing to be vaccinated is thought to be linked to the politicization of the vaccine approvals process, which Trump has attempted to fast-track in the weeks leading up to the election.

Toubman’s position was echoed by representatives of the HIV Medical Association and the Infectious Diseases Society of America during a public comment section of the hearing.

Emily Martin, an assistant professor of infectious diseases epidemiology from the University of Michigan who studies vaccines effectiveness, urged the committee to advise the FDA that EUAs should not allow companies to halt their clinical trials early.

“Without complete and full randomized trial data, we will lack the evidence base needed to monitor and adapt vaccination strategies as needed over the many years these vaccines will be in use,” Martin said. “Ending these trials early will irrevocably hamper our ability to optimize the effective use of the vaccines going forward.”

Goodman agreed that an early EUA could actually leave a manufacturer with too little data to persuade the FDA to issue a full license, though he thought that was not the likeliest of scenarios.

“I think more likely than that, but really, as concerning from a public health point of view would be if … we don’t get adequate enough information to understand how these vaccines compare with each other and perform in terms of their safety and efficacy, we don’t know how to use them in a public health context,” he said. “Which could end up hurting far more people at the end of the day.”

  • Exactly what history justifies listening to STAT? And it is no surprise that the FDA is incapable of making decisions. They seem to be anticognizant of their own guidelines. Get rid of politics and be rational. Politics has even made science a bad word. When Zero Hedge has to write to only responsible synopsis of this pandemic in the USA, you really are in deep trouble.

  • We cannot continue to live like this. We need as many working vaccines as possible as quickly as possible. Society will implode otherwise. If we are forced to endure another year or more of forced social distancing, masks, business closures, remote schools and politicization of every human function, the mental health crisis that results will kill more people than COVID ever did.

  • COVID-19 vaccine is not a silver bullet or a magic wand and will nor replace individual’s contributions of mask wearing, hand washing, and social distancing and Governments role of providing effective testing, contact tracing and isolation of the infected individuals to get us through this pandemic, until herd immunity by vaccination is achieved, which will take months to years. Even with a most effective and safe vaccine, it will take months to years to manufacture enough vaccines of consistent quality, vaccinate the entire populations and achieve protective immunity.
    The only way to control the pandemic quickly is by testing, contact tracing and quarantining those who are infected and their contacts. Please refer to the link for more information. https://www.linkedin.com/pulse/short-term-strategy-controlling-covid-19-pandemic-stop-gupta/?fbclid=IwAR0pU3lRI0C7dHQ_YL9G1EBg66vUzdpQVpkCDyDyYE-aM51sze35vPilJXo

  • The longer we are without a vaccine, the longer we have to put up with all these restrictions, social distancing, forced quarantines on everyone, the cancellations of everything, and everything shutting down, job losses, etc… I and many others do not want to live with all these things for another year or longer! The longer all this crap goes on, the more I want to ironically socially distant myself away from society as a whole and move to a remote location away from everything and everyone and begin a new life permanently there.

  • Helen,

    I viewed the entire session as well. It seems you should of have mentioned snitherer very important point raised by many advisory committee speakers and actually asked for an explanation from the FDA speakers.
    It was about the fact that the efficacy threshold of 50% for approval was consiered as much too low. Would you be eager and line up to be vaccinated by a Covid-19 vaccine which is only 50% effective when it is approved? Not I or my, family for sure! I am certain my sentiment is shared by man others.

    • Just the fact that the general public is watching a vaccine completion and the stock’s for those vaccine manufacturers just keep going up is enough to realize that these so called manufacturers and those invested dont give a crap about the health of people. First of all every therapeutic and every doctor that spoke about their success has been shut down by the media. This I’m sure is due to Bug Pharma, Media Monguls and those that are invested in both. If we have another way of treating this virus successfully , there wont be any need for a vaccine and these investors would stand to lose big time. Also the public have been watching and realize Bill and Melinda Gates foundation not only is involved heavily in vaccine manufacturing but it’s very suspicious why they are. A technocrat is somehow an expert in vaccines and because of his immense wealth is calling the shots. Must think people are blind and stupid. This man is the number one investor in the WHO and isn’t that just amazing how coincidental it is that the WHO is also heavily in vaccines. I’d say this virus was definitely planned. Just as Bill says in his TedTalk and I quote ” there are some things we can do to bring down the population in order to bring down our carbon to 02 or below, and the way we can do that is through medical care, vaccines and reproductive care”. Hmmmm? Vaccines, depopulate?? Reproductive care?? Abortions? Sterilization? Medical care or he should have said fraudulent medical care brought to you by Big Pharma.

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