The Food and Drug Administration's independent advisory committee voted unanimously (18 votes to 0) for authorizing a booster dose for the Pfizer/BioNTech CoVID-19 vaccine. This is for people 65 and over, as well people at high risk due to an underlying medical condition and/or occupational exposed (e.g. healthcare workers). It is recommended that booster doses be administered at least six months following the completion of the first two doses.
If FDA accepts the recommendation of the advisory committee, which it most likely willboosters, then those two groups will be offered an Emergency Use Authorization.
The committee voted against authorization for both groups before voting for it.
The committeeVaccines & Related Biological Products Ad Committee (VRBPAC), felt that there was not enough safety data to make an assessment. This is especially true for young men at greatest risk of developing rare COVID-19 side effects of inflammation around or around the heart (myocarditis, pericarditis). The committee also felt that there wasn't enough evidence to suggest that overall vaccine protection against severe disease, hospitalization and death has diminished sufficiently to warrant a booster shot.
After voting against boosters for everyone, Ofer Levy (a voting VRBPAC member) stated that a third dose "is likely to be beneficial". It's already true for immunocompromised patients. It is likely to be beneficial for the elderly, and it may eventually be recommended for the general public. "I don't believe we are there yet in terms data.
After a turbulent all-day meeting, the votes were cast. Advisory committee members appeared to be irritated at the idea that boosters would be approved for the general public. The Biden Administration, ahead of the FDA review, announced last month that it was ready to start distributing boosters for the vaccinated beginning the week of September 20, Two high-ranking vaccine regulators resigned after the announcement caused frustration and anger within the agency.
Vaccine effectiveness
Marian Gruber, now the FDA's Office of Vaccines Research and Review director, was one of those who resigned. She thanked her staff at the opening of today’s proceedings and noted that it was likely to be her last VRBPAC meeting. She stressed that the decision to approve or deny a booster dose depends on whether it is safe. This involves weighing its potential benefits against its risks. For younger males, that leaves the tricky question of whether the potentially increased risk of myocarditis/pericarditis would be outweighed by the potential benefits of a third dose, given that younger males are already at lower risk of severe disease than older groups and still appear to have high levels of protection from the two primary doses.
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Sara Oliver, CDC epidemiologist, presented a synthesis data showing that while vaccine efficacy has decreased over time but has maintained protection against hospitalizations. Pre-delta vaccine efficacy among adults 18-plus was compared to the most recent post-delta data. The range of vaccine efficacy against infections fell from 72 percent to 92 percent in the pre-delta period to a range between 39 percent and 84 percent in July. Prior to delta, hospitalization vaccine efficacy ranged between 84 and 97 percent. This dropped to 75 to 95 percent in July.
Importantly, the agency's analysis only looked at older adults and not all adults. However, vaccine effectiveness was still strong with an efficacy rate of over 88% in people 75 years old and above. Dr. Oliver pointed out data from Qatar that suggested protection from hospitalization decreased in those aged 60 and older after 25 weeks of vaccination. However, the confidence intervals were very wide.
Experts from Israel also presented data that suggested that vaccine efficacy is decreasing over time. Older people are less protected against severe diseases. By three months, Israel is ahead the US in getting large swathes of its population vaccinated. The country is considered a beacon of vaccine effectiveness. Israel launched a booster shot for all people 16 years and older on July 30, in response to data that suggested a widespread decline in vaccine effectiveness. Israel data shows that boosters have prevented confirmed cases among people over 60 years old and reduced the relative risk of serious disease by more than 10 times. Unfortunately, the US has not had enough time to collect useful safety data since boosters were made available to younger men.
Data concerns
Jonathan Sterne, a statistician at the University of Bristol, warned that it was dangerous to take real-world estimates of vaccine efficacy as they are due to a number of confounding variables. These include the different characteristics of those who are vaccinated and those who have not, and past COVID infections that provide some protection for those who aren't. The timing of vaccinations, risk factors for each group, waves of infection and the timing of vaccinations can all influence vaccine efficacy estimates. These factors can all add up to make vaccine efficacy appear lower than it is. People with compromised immune systems were the first to receive vaccines. This could indicate that there is a problem with their immune system and not a decrease in protection.
It is important to remember that Israel has a different definition of severe disease than the US. They count people who have high respiratory rates or blood-oxygen levels lower than 94 percent. Studies in the US often define severe illness as someone who needs intensive care or hospitalization, or who is unable to fight their infection.
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Pfizer presented its case for boosters. It cited US data that suggested that while protection against infection has decreased, hospitalization protection has not. Pfizer argued that Israel's data suggests a decline in protection against infection and that boosters can prevent an increase in severe diseases and death among those who have been vaccinated.
The FDA and Pfizer presented separate presentations on safety. They reviewed Pfizer's safety data, which only included 306 people aged 18 to 55. Data suggests that third doses of antibody boosters resulted in levels comparable to or greater than those seen after second doses. Similar to the second dose, side effects from a third dose had similar results. The most common effects were pain at the injection site and fatigue.
VRBPAC was convinced by data from Israel that suggests older people could soon be more susceptible to serious disease, hospitalization and death. Booster doses can increase protection. The members were not convinced that boosters should only be given to people over 16 years old, as there is no safety data and no growing risk of severe diseases in the younger group.
Final decisions
In the end, members decided to focus on people 65 years and older, as well as those at high risk. These definitions and cutoffs are not clear. Although the committee didn't have any definitive data, some members suggested that people above 60 or 50 should be considered. The FDA changed the wording of the final voting question to include the 65 cutoff.
The committee also felt it necessary to include those at high risk for severe disease due to underlying conditions. This was because of the potential for further waning and to prevent healthcare systems becoming overwhelmed. An advisory committee for the Centers for Disease Control and Preventionthe Advisory Committee on Immunization Practices, is still working out who might be eligible under these terms. It is scheduled to meet September 22.
Similar to the VRBPAC, the VRBPAC believed it important to include people at high risk for infection from occupational exposure. Boosters shots can reduce the risk of transmission and infection. The committee was concerned about the safety of healthcare workers and frontline workers in a country where hospitals were already struggling under the strain from the virus wave.
Although some people were hoping for a blanket approval for boosters, today's decision disappointed them. However, the committee was happy that it followed science and did not succumb to any pressure from the Biden administration.
Archana Chatterjee is a voting member of VRBPAC and Dean at Chicago Medical School. She said, "I believe this should demonstrate to public that the members are independent from the FDA and that we do bring our voice to the table."
Arnold Monto, chair of VRBPAC, stated that booster doses should be authorized by an EUA. This will allow for easy review of data to determine when boosters may be required for larger groups.
