U.S. vaccine booster policy is in flux as studies add to dissent

WASHINGTON — Almost a month ago, President Joe Biden announced a plan to make coronavirus booster shots available to most adults in the United States eight months after they received their second dose. But a week before the plan is to roll out, its contours are up in the air amid a chorus of dissent inside and outside the government.

The White House has already been forced to delay offering boosters to recipients of the Moderna vaccine, and for now it is planning third shots only for those who received the Pfizer-BioNTech vaccine. Depending on what two public health agencies decide in the coming days, the administration may have to change course again, perhaps restricting extra shots to older Americans and others who are particularly vulnerable to serious illness.

A series of dueling reviews this week illustrated the fierce argument among scientists about whether boosters are needed, and if so, for whom. A study released Wednesday in The New England Journal of Medicine appears to bolster the case made by the White House and its senior health advisers, stating that those who received a third shot of the Pfizer vaccine in Israel were far less likely to develop severe COVID-19 than those who received two injections.

But a review by regulators at the Food and Drug Administration, also made public Wednesday, looked at broader evidence on third doses of the Pfizer vaccine and raised caveats.

And in The Lancet this week, an article written by two of the FDA's top vaccine scientists, among others, argued that there was no credible evidence that the vaccines' potency against severe disease declined substantially over time. The two scientists had announced that they would leave the agency this fall, but their public opposition to the administration's plan caught the FDA's top leaders by surprise and forced the White House on the defensive.

Jen Psaki, the White House press secretary, stressed Wednesday that the administration's most senior health officials — including Dr. Janet Woodcock, the acting commissioner of the FDA, and Dr. Rochelle Walensky, the director of the Centers for Disease Control and Prevention — had signed a statement announcing Biden's booster plan. "Nothing has changed as it relates to the eight top doctors who put out that statement, almost a month ago," Psaki said.

What comes next partly depends on crucial meetings of expert advisory committees to both the FDA, which is responsible for authorizing vaccines, and the CDC, which typically has the final word on vaccination policies.

The FDA committee will meet Friday to discuss and vote on Pfizer-BioNTech's application to offer third shots to people 16 and older. The CDC panel is expected to meet next week. Agency officials are not required to follow the recommendations of their outside expert panels, but they generally do so.

Depending on the experts' reaction to the data review that FDA regulators posted Wednesday, the agency could decide to scale back an authorization. Even if the FDA approves the application as it currently stands, however, the CDC might recommend boosters only for those 65 and older or others who are particularly at risk, according to people familiar with the discussions.

The plan to start offering extra shots next week was announced when the White House was under growing pressure to move on boosters. Because of the highly contagious delta variant, hospitalizations and deaths were soaring, albeit largely among the unvaccinated. Breakthrough infections were becoming more common. France, Germany and Israel were moving faster than the United States to offer boosters. And several governors were publicly calling on Biden to follow suit.

Administration officials have started making the case that offering boosters only to older people would not be a huge change from the president's original plan. Because older adults were vaccinated first, they make up a disproportionate number of those who were vaccinated at least eight months ago.

Several officials suggested that the difference from Biden's original announcement would be minimal as long as some people are offered boosters next week — even if it is only older people who received the Pfizer vaccine.

The backpedaling is a result of what some describe as a double mistake by the White House: First, officials pinpointed a specific week by when additional shots would be rolled out. Second, they announced a broad plan covering the Pfizer and Moderna vaccines before regulators had time to review or even gather all the necessary data.

"We just got things turned around," said Dr. Jesse L. Goodman, a former chief scientist at the FDA. "The administration and the leaders of the scientific agencies who signed on got out in front of any public discussion, airing of the data or vetting of it. That put the FDA and the CDC and their advisory committees in a corner."

Woodcock, the acting FDA commissioner, privately warned that it was risky to publicly announce a timetable, especially for multiple vaccines, according to people familiar with the discussions. The FDA and the CDC meetings in the coming days and Pfizer's application for approval of its booster dose appear to be conforming to the timetable the administration proposed in August.

Like other senior health officials, Woodcock had hoped that booster shots could be offered this month not only for Pfizer and Moderna recipients, but for recipients of Johnson & Johnson's one-dose vaccine as well, according to people familiar with the deliberations. But the administration had to limit its plan to Pfizer recipients, officials said, because neither Moderna nor Johnson & Johnson delivered the expected data in time.

While Biden publicly noted that his strategy depended on regulatory action, he also made the plan sound all but definite. "It's simple," he said at the time. "Eight months after your second shot, get your booster shot."

In interviews, senior administration officials defended the decision to specify a date for the rollout, saying that precious time would have been lost if pharmacies, providers and state officials were not prepared.

The data from Israel, which offered boosters first, was particularly concerning to U.S. health officials.

In the New England Journal of Medicine article Wednesday, researchers said they analyzed health records of more than 1.1 million people in Israel who had received both doses of the Pfizer vaccine at least five months earlier. They found that the rate of severe disease among people older than 60 who received a third shot at least 12 days earlier was nearly twentyfold lower than among those who received two injections.

The FDA has invited Dr. Sharon Alroy-Preis, Israel's head of public health services and a co-author of the study, to describe her country's experience with boosters to the advisory committee Friday. In an interview, Alroy-Preis said Israel had vaccinated more of its population faster than other countries and therefore saw the effect of waning immunity much earlier.

If the United States does not start offering booster shots, she said, more fully vaccinated people will contract severe COVID-19, as they did in Israel. "I am sure of that," she said.

Before Israel's government began offering third shots in August, Alroy-Preis said, people who were fully immunized with the Pfizer vaccine made up at least half of severely or critically ill COVID-19 patients. The number of those patients is now less than half what officials had previously projected, she said, and the spread of the virus has slowed.

"We are beginning to control the fourth wave," Alroy-Preis said, "mainly by vaccinating people with third doses."

Yet vaccine experts said Wednesday that what the Israeli data show — that a booster can enhance protection for a few weeks in older adults — is unsurprising and does not necessarily indicate long-term benefit. There are differences between Israel and the United States that could lead to different outcomes, scientists have warned.

The FDA cautioned its advisory committee Wednesday against putting too much weight on the experiences of other countries.

"While observational studies can enable understanding of real-world effectiveness, there are known and unknown biases that can affect their reliability," the regulators wrote in a briefing paper. Studies conducted in the United States "may most accurately represent vaccine effectiveness in the U.S. population," they added.

The FDA's analysis also noted that Pfizer had gathered data on immune responses against the delta variant in only two dozen people. Pfizer said in a separate filing that one month after a third injection, levels of neutralizing antibodies against the delta variant were about five to seven times higher than they were a month after the second dose.

Whatever the FDA decides, it should clearly and publicly explain its reasoning, said Dr. Joshua Sharfstein, a vice dean at the Johns Hopkins Bloomberg School of Public Health and a former principal deputy commissioner of the agency.

"FDA does the best, in situations when there are strongly held but conflicting views, when they're forthcoming with the data and really explain decisions," he said. "It's important for the FDA not to say, 'Here's our decision, mic drop.'"

He added, "It's much better for them to say, 'Here's how we looked at the data, here are the conclusions we made from the data, and here's why we're making the conclusions.'"

This article originally appeared in The New York Times.