Pfizer COVID Booster Recommendations From CDC Panel Narrower Than FDA's EUA
Executive Summary
Advisory Committee on Immunization Practices fails to pass an interim recommendation endorsing third dose of vaccine in health care workers and others at risk of occupational or institutional exposure, with panelists raising concern that the target population was overly broad.
A US Centers for Disease Control and Prevention panel on 23 September recommended a third or “booster” dose of Pfizer Inc./BioNTech SE’s Comirnaty COVID-19 vaccine for a broad swath of the American public, including those age 65 years and older or with comorbid medical conditions, but failed to support use for health care workers and others at risk for occupational exposure.
The Advisory Committee on Immunization Practices’ interim recommendations for a booster dose came in a complicated series of votes at the end of two-day meeting. (See box.)
The increase in “no” votes as the voting went along reflected panelists' discomfort about the lack of available data on waning efficacy of the primary two-dose vaccination series, and increasing questions about the benefit/risk balance, in the target populations.Panelists also worried that by voting to recommend boosters in populations for which there were little supporting data, they would be sending the incorrect message to affected individuals that the primary two-dose vaccination series was no longer effective.
The end result is a series of interim policy recommendations that seem likely to confuse the American public and challenging to implement at the state and local levels. They also seem unlikely to quell the debate in the US about whether boosters are really necessary or justified given evidence of continuing efficacy of the primary series against severe disease and hospitalizations, concerns about myocarditis in younger people post-vaccination, and global equity concerns – with the latter issue not discussed by ACIP.
EUA Amendment
On 22 September, the FDA authorized use of a single booster dose of the Pfizer/BioNTech vaccine in the following populations at least six months after completion of the primary series:
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Individuals 65 years of age and older;
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Individuals 18-64 years at high risk of severe COVID-19; and
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Individuals 18-64 years whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.
The FDA’s clearance, coming in the form of an emergency use authorization amendment, closely tracked the recommendations of its Vaccine and Related Biological Products Advisory Committee, which voted overwhelmingly against broad licensure of a booster in the 16-and-older population. (Also see "Pfizer Booster Dose Authorization From US FDA Has Age Caveat: At-Risk Populations 18 And Up" - Pink Sheet, 22 Sep, 2021.)
The FDA action left the task of further delineating the populations recommended for a booster dose to ACIP, which began its meeting before the EUA amendment was announced and continued the proceedings the next day. (Also see "US FDA Panel Rejects Pfizer's Broad COVID Booster Plan But Backs Narrower Authorization For Third Vaccine Shot" - Pink Sheet, 17 Sep, 2021.)
Greatest Need In Older Individuals
ACIP was presented data suggesting the greatest benefit with boosters would be derived from use in individuals ages 65 years and older. In this group, there were significant declines in vaccine effectiveness (VE) against infection, with smaller VE declines against hospitalization.
Among adults younger than age 65, the vaccines remain effective in preventing hospitalization and disease, according to data presented by the CDC. Concerns about the risk of myocarditis also increased as the target age groups got younger.
In the 65-and-over age group, the number needed to vaccinate to prevent one hospitalization over six months was 481; in the 18-29 age group, this number jumped to 8,738, the CDC said.
In the 65-and-over age group, the number needed to vaccinate to prevent one hospitalization over six months was 481; in the 18-29 age group, this number jumped to 8,738.
There are limited data currently to evaluate VE by underlying conditions, and the effectiveness among health care and other frontline essential workers is similar to the estimates for the general population of the same age, according to data presented to the committee.
ACIP was unanimous (15-0) in its support for a booster recommendation in the 65-and-older population, with slightly less support (13-2) for use of boosters in 50-64 year-olds who have underlying medical conditions that increase the risk of serious disease.
The benefit-risk equation tilted further toward the risk side with a 9-6 vote in support of a permissive recommendation, based on individual benefit/risk considerations, for use in 18-49 year-olds with underlying medical conditions.
Matthew Daley, senior investigator at Kaiser Permanente in Colorado, voted in favor of this interim recommendation but not without trepidation. There are individuals in the 18-49 age group who may benefit from a booster, such as a 35 year-old with cystic fibrosis, he said. However, “I recognize that fortunately the primary series is providing good effectiveness and there’s a lot more uncertainty here.”
Drexel University pediatrics professor Sarah Long voted against the recommendation. “As we went down in age” there were “no data that those who have underlying medical conditions have a more rapid wane, especially in very young individuals,” she said. “And knowing that the risk of myopericarditis in the 18 year-old age group is substantial, I agree that this is not a simple decision.”
Occupational Exposure Category Too Broad
The lone negative vote (6 yes, 9 no) came on the final proposed interim recommendation related to occupational or institutional exposure. This recommendation was intended to capture the authorized use in those whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19.
In its authorization announcement, the FDA said this category would encompass health care workers, teachers, day care staff, grocery workers and those in homeless shelters or prisons. The ACIP’s proposed recommendation also was intended to cover caregivers of young children or other at-risk individuals who cannot be vaccinated, and to prevent COVID-related absenteeism among medical professionals to minimize the stress on the health care system.
However, many ACIP members found the wording of the proposed interim recommendation overly broad.
It “just seems uncharacteristically openly ended for the lack of data of need in any of these groups,” Long said.
Pablo Sanchez, director of clinical and translational research at Nationwide Children’s Hospital, agreed. “We might as well just say just give it to everybody 18 and over,” he said. “We have a really effective vaccine and it’s like saying that it’s not working, and it is working.”
With the fourth recommendation “we start moving into the territory where we’re really not talking about direct benefit to the person who is being vaccinated, we’re talking about indirect benefit to the people surrounding them,” said Wilbur Chen, professor of medicine at the University of Maryland.
“We know that indirect benefit is largely to be gained by people getting their primary series,” Chen said. “It’s not the answer to give them boosters, especially for this age group that doesn’t have underlying medical conditions, they don’t have predictors that would put them at the highest risk for severe effects with COVID infection.”
Chen also warned about operational challenges with the fourth recommendation. “The implementation part of this is going to be fraught with such complexity that people who have great health literacy will get boosters, and they’re not really the ones who are going to get the best incremental benefit out of this.”
ACIP seems likely to revisit the recommendation on booster doses for those at risk of occupational exposure at a meeting in the near future.
The CDC said that even for those populations in whom booster doses are recommended, individuals still would be considered “fully vaccinated” after they complete the primary vaccination series.
Desire To Mix And Match
In addition to concerns that booster recommendations could imply the primary vaccination series is no longer effective, panelists worried about sending a negative message to those individuals who received their primary series with either the two-dose Moderna, Inc. mRNA vaccine or the one-dose Janssen Biotech Inc. adenovirus-based vaccine.
Throughout the meeting ACIP members lamented the absence of data on “mixing and matching” of the Pfizer booster dose after receipt of a primary series with another vaccine. They pushed for any ACIP recommendation to allow flexibility about using the Pfizer booster in conjunction with the other authorized vaccines.
However, the FDA’s authorization covers use of a Pfizer booster only after completion of the two-dose series with the same vaccine. The EUA fact sheet for the vaccine states that data are not available to inform interchangeability with other authorized vaccines to complete the primary vaccination series or booster dose.
“That’s going to leave half of the people immunized in this age group having received a vaccine and being told their at risk now for waning immunity and hospitalization unable to get a booster dose,” Long said. “That’s a big public health panic that we would like to avoid.”