FDA: A Covid-19 vaccine before Election Day is unlikely

Food and Drug Administration officials on a key committee said Thursday they were not planning to make a decision about granting emergency approval for a Covid-19 vaccine just yet. This all but ends the chances of a vaccine getting the green light in the US before the November 3 presidential election, and likely over the next month.

The Vaccines and Related Biological Products Advisory Committee was convened to go over the early results of Covid-19 vaccine clinical trials, the benchmarks to approve a vaccine candidate, and how to maintain safety throughout the process. However, no decisions are on the agenda.

“Of note, the committee is not asked today to vote on any issues discussed,” said Marion Gruber, director of the Office of Vaccines Research and Review at the FDA during the meeting.

President Trump has made it clear that a Covid-19 vaccine would improve his electoral prospects, and he has been leaning on regulators like the FDA to approve a vaccine on this timeline. That’s raised concerns that the agency would yield to political pressure and grant approval to a vaccine before it’s ready.

Trump also put out a video earlier this month saying that a vaccine would be cleared for use soon after the election. “We’re going to have a great vaccine very, very shortly,” Trump said. “I think we should have it before the election, but frankly the politics gets involved and that’s okay, they want to play their games, it’s going to be right after the election.”

But while vaccine development is proceeding in record time, researchers and other experts have said many times such a deadline is unlikely. Even the Trump administration’s own health officials at the Centers for Disease Control and Prevention have already said November is nearly impossible.

There are now 11 vaccines in phase 3 trials, including candidates from companies like Moderna, AstraZeneca, and Pfizer. However, some of these companies have only just completed enrollment in large-scale clinical trials, at which point they will have to administer the vaccine and observe infection patterns, which could take months.

And although there’s currently no evidence that the White House is directly meddling in vaccine research, some scientists worry that the president’s public pronouncements about a vaccine — especially ones so nakedly tied to his political prospects — are a form of interference that could undermine the fragile public confidence needed to deploy it successfully.

Trump has “created enough perception of political interference that there may not be deep trust in a vaccine, even if it’s a good product,” said Nicole Lurie, who led emergency preparedness at the Department of Health and Human Services (HHS) under President Barack Obama. “There is incredible public skepticism of the [FDA] because of what’s happened with prior emergency use authorizations, and because the president appears to continue to try to mess with the system.”

However, according to researchers, it’s unlikely the FDA would compromise a vaccine, given the vastly higher stakes for public health. Even getting to the point of considering emergency use for a vaccine would require much more information than it has now, and gathering that data requires several critical and time-consuming steps.

Why getting a vaccine approved by November is nearly impossible

Prior to the coronavirus, the fastest a vaccine had ever been developed was four years (for mumps). Most vaccines have taken a decade or longer.

But with the Covid-19 pandemic, scientists and governments have poured a staggering amount of money and know-how into the vaccine effort. That’s led to rapid progress.

It took researchers just over two months between the time the virus’s genome was sequenced and when phase 1 human vaccine trials began. There are now 11 vaccine candidates in phase 3 clinical trials, the final step before a vaccine gets the green light for widespread use.

That’s why some scientists are optimistic that a vaccine could gain approval by the end of the year or early 2021.

But phase 3 trials are slow and tedious. There’s little that can be done to speed them up, and they’ve only just begun. Although the Russian government recently said it has a Covid-19 vaccine ready to go, other researchers have warned that the vaccine, known as Sputnik V, didn’t go through this critical step and was tested in only 76 people. And even if it is a viable vaccine, it would still need to gain FDA approval before it could be used in the US, which demands more data.

Health workers prepare to examine volunteers for a Covid-19 vaccine phase 3 trial.
Chandan Khanna/AFP via Getty Images

Jonathan Zenilman, a professor at the Johns Hopkins University School of Medicine who has overseen clinical trials for vaccines, explained that Covid-19 phase 3 trials are large, aiming to enroll 30,000 participants each. For example, Moderna, a company developing an mRNA Covid-19 vaccine, is one of the teams that’s furthest along. It was the first in the US to start enrolling participants across 89 sites for its phase 3 trial.

Phase 3 requires recruiting participants from more diverse backgrounds compared with those in earlier testing stages in order to better represent the population at large, including people with some preexisting health conditions. (Participants are screened to ensure they don’t have conditions like immune system disorders that could cause complications with a vaccine.)

These participants also have to consent to being tracked by scientists for the duration of the trial, which is typically two years. They’re randomly split into groups that receive either the vaccine or a placebo. In a double-blind trial, neither the recipients nor the people administering the vaccine know at the outset who received the vaccine. That ensures participants won’t change their behavior in a way that could interfere with the trial (a person who knows they have a Covid-19 vaccine could end up taking more risks, for example).

Finding tens of thousands of people who meet all these requirements for a phase 3 trial is tedious. Simply enrolling enough people is a process that can take months.

Although some Covid-19 vaccine phase 3 trials began in July, few have completed the enrollment process. Moderna said it is close to wrapping up enrollment.

After getting consent from volunteers and enrolling them in the trial, you have to give them the vaccine. Many Covid-19 vaccine candidates require two doses spaced up to four weeks apart, so just getting someone the full vaccine dose can take around a month. For most of the vaccine candidates in phase 3 trials, that would take them well into, if not past, October.

“Then you have to wait for people to get Covid, and you can’t do anything with the data until you have a certain number of Covid cases,” Zenilman said. To get a statistically meaningful result, researchers typically wait until they see around 150 infections in their group. At that point, they can “break the blind” and see who got the vaccine and who got the placebo — and compare the numbers to see whether it’s working.

Right now, many places in the US are still maintaining pandemic control measures such as social distancing and mask-wearing. Such tactics help control the spread of the virus, but for a vaccine trial, they also limit how quickly research teams can get the data necessary to draw conclusions about whether the vaccine is working. That’s why researchers are aiming to test their vaccines in rising Covid-19 hot spots.

There is also no guarantee that any vaccine will clear clinical trials. And the first vaccine to gain approval would not be available for widespread use right away. Health officials have to contend with the logistics of manufacturing, distributing, and administering the millions of doses needed to control the Covid-19 pandemic, which could take years.

Moderna CEO Stéphane Bancel said on September 30 that his company’s vaccine, which is one of the candidates furthest ahead in clinical trials, would not be ready for widespread distribution until next spring. He told the Financial Times that the company wouldn’t even consider applying for an emergency use authorization until November 25.

It’s also likely that no single vaccine will be suited to everyone. Several vaccines will be needed to protect different demographics, including older people, those with weaker immune systems, or those with certain preexisting health conditions. So even after the first Covid-19 vaccine gets approved, some people will still have to wait for other clinical trials to conclude.

Officials say they will not budge on vaccine safety and efficacy rules

FDA regulators are adamant that a vaccine will not be approved until it is demonstrated to be safe and effective. According to FDA guidelines, a vaccine needs to provide protection against the coronavirus for at least 50 percent of the people who get it. The safety benchmarks are higher for vaccines than for other drugs because vaccines are given to vastly more people, which magnifies infrequent problems. And since vaccines are given to healthy people rather than those who are already sick, there is a lower tolerance for side effects.

But at the same time, HHS launched the $10 billion Operation Warp Speed in June with the explicit aim of delivering 300 million doses of a Covid-19 vaccine by January 2021.

In an August 7 editorial in JAMA, FDA Commissioner Stephen Hahn acknowledged the tension between the need for speed and the need to hew closely to established rules.

Hahn and his co-authors, Anand Shah and Peter Marks, wrote that “the emphasis on speed has provoked public anxiety about the safety and effectiveness of vaccines developed on expedited timelines. Among the concerns are that the regulatory standards for approval will be lowered under political pressure for a vaccine.”

FDA Commissioner Stephen Hahn testifies before the Senate Health, Education, Labor and Pensions (HELP) Committee hearing on Capitol Hill in Washington DC on June 30, 2020 in Washington,DC.
FDA Commissioner Stephen Hahn said his agency would not bend the rules to approve a Covid-19 vaccine.
Kevin Dietsch/AFP via Getty Images

However, Hahn and his co-authors also wrote that “there is a line separating the government’s efforts to focus resources and funding to scale vaccine development from FDA’s review processes.” In other words, the FDA says it will not compromise its standards for approving a vaccine, despite pressure for faster results.

But what about the emergency use authorization (EUA) process? Could the FDA create a limited exception for a vaccine like it did with hydroxychloroquine?

Marks, the director of the Center for Biologics Evaluation and Research at the FDA (the body that governs vaccine approval), said the agency could do that, in theory. But as with the agency’s standard process, the rubric is stricter for a vaccine than for a drug, and regulators would still need to see data demonstrating that a vaccine meets the minimum benchmark of preventing infection in 50 percent of people who have been vaccinated.

“I think as we think about EUA here, the calculus for a vaccine is going to be different than the calculus for therapeutic,” Marks told reporters at the National Press Foundation on August 12. “I think we … optimally would like to see the data that’s from a trial that’s reached its efficacy endpoint.”

That would come near the end of a phase 3 trial, which, again, is unlikely to yield results for months. So there may not be enough evidence to warrant vaccine approval before the November election, even on an emergency basis.

And if there were political meddling to push out a vaccine before it’s ready, in spite of all these constraints, there would be strong opposition among the career scientists at the FDA. “I think you would see a revolt at the agency,” Zenilman said.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in a recent interview with Today, Explained host Sean Rameswaram that he is also confident the process will be transparent.

“The FDA has pledged publicly multiple times that they will not approve a vaccine unless they’ve established that nonpolitical scientists agree that it’s safe and effective … And if it turns out somebody tries to force it out, I tell you, I will be one of the first ones that will object to that,” Fauci said.

Trust is critical for deploying a Covid-19 vaccine. But trust is fragile.

A vaccine can’t end the Covid-19 pandemic on its own. It has to be given to enough people to achieve herd immunity, at which point a large enough percentage of a population is protected against the virus so that it can’t easily spread.

Even in the most ideal scenario with a highly effective vaccine, getting to herd immunity would require immunizing millions of people. And already, many in the United States are saying they wouldn’t get vaccinated. A Gallup poll conducted July 20 to August 7 found that one-third of Americans said they would not get an approved Covid-19 vaccine if it were ready immediately. A CNN poll conducted August 12-15 found that 56 percent of Americans said they would get a vaccine, a decline from 66 percent in May.

Whether due to general hesitancy around vaccines or swirling conspiracy theories, public health researchers are concerned that if enough people don’t elect to get immunized, the Covid-19 pandemic will persist.

That’s why even the appearance that political considerations influenced vaccine approval could be dangerous.

Vaccine makers have pushed back against the pressure to speed up development even further as well because if the public perceives a vaccine was rushed, it could make people hesitant to use their product.

“The perception of political pressure and the perception of things being hurried really risks trust,” said Jesse Goodman, a former chief scientist at the FDA who’s now a professor of medicine at Georgetown University. “It’s not just trust in this Covid vaccine, but trust in the whole public health response to Covid and trust in vaccines in general.”

In March, after the president repeatedly promoted the anti-malaria drug hydroxychloroquine as a treatment for Covid-19, the FDA issued an emergency use authorization for the medicine, despite scant evidence of its effectiveness. In June, the FDA revoked this authorization.

Restoring that trust will take time. It will require transparency about the progress and results of clinical trials, as well as how decisions are made in federal agencies. It will also demand clear and coherent messaging.

But even that might not be enough.

“Personally, I think it will take a new president and new leadership at the top of the FDA before we’re going to be at a point where the public can start to have more trust,” said Lurie.

Which means that even with the urgency of thousands of people dying, taking the time to get a vaccine right is critical — from the vaccine itself to how it’s tested, documented, communicated, and administered. Rushing will likely only cost us more time.

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