Science’s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.
President Donald Trump’s name was not mentioned once yesterday during a webcast meeting where a who’s who in COVID-19 vaccine development debated what’s ahead in the next few weeks and months.
Yet the shadow of the U.S. president—recovering from COVID-19 at the White House and tweeting he was “FEELING GREAT!”—hovered over the 3-hour symposium, organized by the Johns Hopkins Bloomberg School of Public Health and the University of Washington.
Trump has aggressively pushed for a COVID-19 vaccine to be rolled out before Election Day and many scientists and public health officials worry he will interfere with the approval process. The meeting, about “preserving the scientific integrity of getting to COVID-19 vaccines,” was convened primarily to allay those fears. Any vaccines the U.S. Food and Drug Administration (FDA) deems worthy of widespread distribution will have compelling data that they are safe and effective, a united front of scientists, bioethicists, and regulators emphasized—and that is not going to happen before 3 November. Their message was: No need for alarm, we’ve got this.
“Despite a lot of the political noise, the science is going well,” said Francis Collins, director of the National Institutes of Health (NIH). “I know there’s a great deal of anxiety about mischief here. It would be pretty darn hard for mischief to derail this process. And I hope everybody can start to get calmed down about that.”
The unprecedented amount of “cutting-edge research” underway should serve as “an antidote to the attacks on science that have been running rampant in our society,” said former Democratic presidential candidate Michael Bloomberg, the public health school’s main benefactor.
Mischief has occurred already during this pandemic. Several participants complained that Trump has repeatedly strong-armed government science agencies to alter their responses to the pandemic coronavirus. He touted hydroxychloroquine as an effective treatment and preventive for COVID-19 without evidence and called convalescent plasma therapy a “historic breakthrough,” to the dismay of scientists advising him. As for vaccines, they are “coming momentarily,” Trump proclaimed on Monday after returning from a 3-day stay at the Walter Reed National Military Medical Center.
The threat of political interference, along with the scientific uncertainties about the deadly virus, has created “high levels of mistrust and confusion in the community,” said Kathleen Neuzil, who directs the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine and co-leads an NIH-sponsored clinical trial network for COVID-19 vaccines. Surveys show the U.S. public is increasingly hesitant about taking a COVID-19 vaccine even if it receives FDA approval. If a substantial part of the population were to decline an effective vaccine, “we’ll be working from home for long periods of time,” said Peter Marks, head of the FDA division that oversees vaccines, who spoke from an office in his basement. “We need to get back to normal lives.”
COVID-19 vaccines are widely expected to receive an initial blessing from FDA—and be rolled out by the millions— through the hotly debated emergency use authorization (EUA) pathway, which allows the early approval of medicines that “may be” effective. An FDA guidance issued in June suggested a vaccine could obtain EUA status if it shows a minimum of 50% efficacy, which is far from ideal but could still help spare people from illness.
Shortly before yesterday’s meeting, FDA—in defiance of substantial pushback from the White House—issued new, more detailed guidance for COVID-19 vaccinemakers seeking EUAs. Predicted to delay approvals, the revamped guidance stipulates that companies need to collect safety data for at least 2 months after roughly half the participants in the trial have received their last dose. (Most COVID-19 vaccines are given two doses 21 to 28 days apart.) Side effects typically occur within that 2-month time frame, said Marks, who explained that the rule aims to “end up increasing trust in vaccines.”
Trump or Secretary of Health and Human Services Alex Azar could issue an EUA over the objection of FDA, but CEOs from the leading vaccine manufacturers, well aware their products must win over a skeptical public, on 8 September pledged to follow FDA’s guidance. (Albert Bourla, CEO of Pfizer, has signed the pledge, although he also has bolstered Trump’s optimistic message, suggesting the company could have efficacy data as early as this month.) The manufacturers won’t go along with any political schemes, said Scott Gottlieb, a former FDA commissioner who’s now on the board of Pfizer. “There are a few moments I could think of where so much political dust was created by political officials for so little actual practical effect,” he added.
Still, there is debate even among scientists about how stringent the criteria should be for FDA to issue an EUA for a COVID-19 vaccine. Lawrence Corey of the Fred Hutchinson Cancer Research Center, who co-leads NIH’s COVID-19 vaccine trials network and helped put the symposium together, called this issue “the elephant in the room.” He says FDA’s guidelines put the bar too low because they only ask for a 50% reduction in relatively mild symptoms such as fever, cough, fatigue, and loss of taste or smell. Instead, Corey argued that vaccines should also be shown to prevent what he called “medically complicated” COVID-19, which translates to being sick enough to seek care.
Corey went into the fine details of the trials supported by Operation Warp Speed, the U.S. COVID-19 vaccine effort. (Pfizer, Moderna, AstraZeneca, and Johnson & Johnson—which make four of the leading candidates—have made their trial protocols public as a sign of their transparency.) The trials each have 30,000 to 45,000 participants who are randomly assigned to receive either the vaccine or a placebo. To assess whether a vaccine works, trial designers have calculated they must accrue at least 150 “events”—jargon for a participant becoming infected with COVID-19 and developing symptoms.
Pfizer is conducting its own studies, but the other candidates in Warp Speed’s portfolio are part of trials that are overseen by a single data and safety monitoring board, an independent expert group that takes peeks at the otherwise blinded data and can stop trials early if participants are harmed or convincing efficacy signals surface. The board is scheduled to examine the data from each study when there are about 50 events and again when there are 100. In Pfizer’s studies, the first look will happen after only 32 events.
By Corey’s calculations, only about one in five COVID-19 cases qualifying as an event would be “medically complicated,” meaning there might only be 10 when a trial ends after 50 events. That would make “true assessment of vaccine efficacy in this important area skimpy at best,” he said. The study’s projected timelines suggest the period between accruing 50 and 150 events is only 7 weeks. “One triples the amount one could learn about vaccine efficacy” in those weeks, Corey said. “We must insist these trials be allowed to provide the scientific underpinnings of our COVID-19 vaccination strategy.”
Some researchers contend that if a vaccine prevents mild symptoms, it likely will prevent severe disease as well. On the other hand, William Haseltine, a pioneering HIV/AIDS researcher who left academia and started several biotechnology companies, argued in Forbes magazine last month that FDA standards should require an even higher standard than Corey calls for: prevention of infection.
Making sure COVID-19 vaccines go through a solid approval process and building confidence in them is one of the most important issues in this pandemic, Johns Hopkins epidemiologist Chris Beyrer, the event’s co-convener and moderator, told Science afterward. “Having utterly failed the ground game, we now are in a position where there’s so much community transmission, we don’t get out of this without a vaccine,” Beyrer said. “So the idea that the last potential tool in the toolkit to get us out of this COVID epidemic in the U.S. could be scuttled for a brief political bounce and setback is a potentially catastrophic outcome. And that’s why we’re so concerned.”
The recovering COVID-19 patient whose name wasn’t mentioned saw it differently. “New FDA Rules make it more difficult for them to speed up vaccines for approval before Election Day,” Trump tweeted. “Just another political hit job!”
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