Issue with lack of nuance in FDA panel kid-dose vaccine vote

 An FDA advisory panel recommended emergency use authorization (EUA) of a two-dose regimen (10 μg apiece) of Pfizer-BioNTech's COVID-19 vaccine, administered 3 weeks apart, for children ages 5-11 years.

The Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted 17-0, with one abstention, that the benefits outweighed the risks of the vaccine in this population.

Several members of the committee expressed irritation at the "binary choice" of either voting "yes or no" on the recommendation, as opposed to a more nuanced recommendation. However, Peter Marks, MD, PhD, director of FDA's Center for Biologics Evaluation and Research (CBER) charged VRBPAC at the beginning of the meeting that their job was not to decide who would get the vaccine within the population, nor to discuss or consider vaccine mandates.

Michael Kurilla, MD, PhD, of the NIH National Center for Advancing Translational Sciences, was the one abstention. He pushed for more nuance in the question, namely alternate dosing for the children with prior COVID infection.

Ultimately, the committee was swayed by the idea that if they did not vote to recommend the vaccine, it would not be available to children with high-risk medical conditions or medically vulnerable children in need of protection.

"If we try to approve this for some subset of the group, that could potentially lead to a situation where this becomes a vaccine that gets used more" by those of higher socioeconomic status with access to it, Marks noted.

"I understand why the question was asked that way, but I certainly don't like it," said Michael Nelson, MD, of the University of Virginia School of Medicine in Charlottesville. He added that a model of shared clinical decision-making with "risk-informed" parents and their healthcare providers made the most sense to him.

Most members also seemed torn about such a broad authorization, particularly that states might mandate it in order for kids to go to school. Other issues at play were the fuzzy issue of vaccine-associated myocarditis risk, as well as CDC data that indicated that about 40% of children in this population had previously been infected with COVID-19.

"It's always nerve-wracking when you're asked to make a decision for millions of children based on ... [data from] a few thousand children," said Paul Offit, MD, of Children's Hospital of Philadelphia.

Ultimately, he said it came down to "do we know enough" based on the information available, and concluded that while more will be known once a larger population of children are vaccinated, there was enough data for him to vote "yes."

"When I look at this question, it's pretty clear that the benefits do outweigh the risks," said Amanda Cohn, MD, MPH, of the CDC in Atlanta. "We don't want children to be dying of COVID, and we don't want them in the ICU."

Other committee members brought up the impact school closures have had on children's learning, and the need for parents to be able to protect their children in areas where mask mandates are not enforced.

Data in FDA briefing documents was primarily from phase II/III of the phase I/II/III study C4591007, which had 3,109 participants who received vaccine and 1,528 who received placebo. It was made up of two cohorts: Cohort 1, with 1,444 in the vaccine group and 714 in the placebo group, each with at least 2 months of follow-up safety data, and cohort 2, who had a median of 2.4 weeks of follow-up data at the time of data cutoff.

The vaccine met immunobridging success criteria, FDA staff said, with increases in neutralizing antibody geometric mean titers among children ages 5-11 versus individuals ages 16-25, as well as comparable seroresponse rates among the two groups versus baseline.

A descriptive analysis found 90.7% vaccine efficacy (VE; 95% CI 67.4-98.3%), with three COVID cases in the vaccine group and 16 in placebo. None of the cases met the criteria for severe COVID. About 20% who acquired COVID-19 had comorbidities, and most infections occurred during July-August 2021.

Adverse events (AEs) were similar to other populations, with no cases of myocarditis or pericarditis, anaphylaxis, or deaths. The most common AE was fatigue (39%), followed by headache (28%) and muscle pain (12%). Most systemic AEs were mild or moderate, and resolved 1-2 days after onset, FDA staff noted.

FDA staff also conducted a series of models that measured symptomatic COVID-19 cases, hospitalizations, ICU admissions, and death compared to excess myocarditis/pericarditis cases, hospitalizations, ICU admissions, and death.

They found that the benefits were highest among kids ages 5-11 in the scenarios using the Delta-surge peak incidence, high VE, and higher COVID death rate, and lowest in scenarios with the lowest incidence.

They also pointed out that they used a "conservative assumption" for myocarditis risk, namely healthcare claims from adolescents ages 12-17, and if the risk is lower among younger children, "the benefit-risk balance would be more favorable."

VRBPAC ultimately concluded that any narrowing of these recommendations could be left up to the CDC Advisory Committee on Immunization Practices (ACIP).

Oveta Fuller, PhD, of the University of Michigan in Ann Arbor, said that a "yes" vote meant that in hindsight, the committee could look back on their decision favorably to give parents the choice to vaccinate their kids.

"We want to make the option available for what it might do to help the children as well as others in this pandemic," she said.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/95278