Scientists at the Food and Drug Administration presented an analysis late Friday showing that the protection offered to children between the ages of 5 and 11 by the Covid vaccine developed by Pfizer and BioNTech “would clearly outweigh” the risk of myocarditis, a heart-related side effect, that the vaccine appears to cause.
The FDA’s analysis was made public ahead of a Tuesday meeting of outside scientists convened to make a recommendation on authorizing the vaccine for children in that age range. An agenda for the meeting shows sessions dedicated to the vaccine’s effectiveness, and to the potential risk of myocarditis, an inflammation of the heart. The FDA is not bound by the votes of its advisory committees, but it generally follows their advice.
New data from Pfizer were also made public on Friday. They show that the vaccine is about 91% effective in preventing Covid-19 in 5- to 11-year-olds.
“While benefits of vaccination were highly dependent on Covid-19 incidence, the overall analysis predicted that the numbers of clinically significant Covid-19-related outcomes prevented would clearly outweigh the numbers of vaccine-associated excess myocarditis cases over a range of assumptions for Covid-19 incidence,” agency researchers wrote.
However, the researchers noted, if the rate of Covid-19 was to fall to levels seen in June 2021, there would be more vaccine-associated myocarditis cases than Covid-19 hospitalizations. But even then, the FDA staff said, given the more severe nature of Covid-19 hospitalization, “the overall benefits of the vaccine may still outweigh the risks under this low-incidence scenario.”
Much of the committee’s discussion is likely to center on the benefits of the vaccine, which dramatically reduces the chances a child will become infected with SARS-CoV-2, the virus that causes Covid-19, as well as its potential risks. In older boys and young men, the vaccine has been linked to myocarditis. It has occurred in somewhere around 1 in 10,000 boys and men between the ages of 16 and 19 who received a second dose, though estimates of the risk vary.
New data in the briefing documents show that the Pfizer/BioNTech vaccine not only cuts the risk of infection, but also reduces the risk of symptomatic Covid-19 in children who do become infected with SARS-CoV-2. Among the 1,518 children in the study who received the vaccine, there were three cases of symptomatic Covid-19. Among the 750 children who received placebo, there were 16 cases of the disease — meaning the vaccine was 90.7% effective. Previously, only data about children’s ability to produce antibodies against Covid-19 after vaccination, and not its effectiveness at preventing illness, were available.
Symptoms among the vaccinated children were very mild. None had fevers. By contrast, 10 of the 16 children who were not vaccinated who developed Covid-19 developed fevers. Common side effects were generally similar to those caused by the adult vaccine, and included headaches and fevers. The pediatric shot is 10 micrograms, or one-third the adult dosage.
Of the volunteers in the study, 52% were male, 79% were white, 6%% were Black, and 6% were Asian American.
Data were also included in an expansion group of 1,591 additional children who received the vaccine and another 788 who received placebo, although all have not been followed for 2.5 weeks. For these children, information is available only about side effects. It appears that the FDA may be willing to make a decision on the vaccine without data from this extension study.
Because children are less likely to experience severe consequences of Covid-19, the panel will likely discuss whether the benefits of protection outweigh the small risk of myocarditis or other side effects. Covid-19 itself can cause myocarditis at a much higher rate than the vaccine.
Too few younger individuals have been treated to have a clear idea of the risk of myocarditis. Researchers still do not fully understand why it occurs. Although some patients with vaccine-induced myocarditis have needed intensive care, the FDA said most had their symptoms resolve with “conservative management.”
Because myocarditis occurred only rarely in clinical trials, it’s difficult to estimate exactly how often it occurs. In its briefing documents, the FDA said that myocarditis and pericarditis, a related inflammation of the heart’s lining, were reported to the U.S. government’s Vaccine Adverse Events Reporting System (VAERS) at a rate of 71.5 cases per million in vaccinated males ages 16 to 17 and 42.6 cases per million in males ages 12 to 15. That equates to about one case per 12,000 for 16- to 17-year-olds and one case per 24,000 for 12-to-15-year-olds.
But the FDA also analyzed a database of claims from Optum, part of the insurer UnitedHealth Group. In that database, the estimated excess risk of myocarditis and pericarditis approached 200 cases per million in fully vaccinated males aged 16 to 17, and 180 cases per million in vaccinated males aged 12 to 15 years of age. That’s about one case per 5,000 vaccinated boys.
The question, though, is not just what is the risk of myocarditis, but whether the benefit of the vaccine outweighs that risk. And the benefit of vaccinating anyone depends on how many cases of Covid-19 are occurring.
The FDA modeled how many hospitalizations would be prevented by vaccinating a million boys in the 5 to 11 age range at six different points in the pandemic. Most of the time, the vaccine would prevent 200 to 250 hospitalizations per one million vaccinated boys. But at one point, in June 2021 when cases were plummeting nationwide, the vaccine would only have prevented only 21 hospitalizations per one million boys.
At any point, the number of myocarditis hospitalizations caused by the vaccine would be the same: the FDA estimated it as 98 hospitalizations per million boys vaccinated. So normally, even in the highest-risk group, the number of Covid-related hospitalizations prevented would be double the number of hospitalizations due to myocarditis. But when the virus is under control, the number of myocarditis-related hospitalizations in boys in this age group would be slightly more than Covid-related hospitalizations because Covid-19 cases would be so low.
The FDA argues that even in this case, outcomes for those hospitalized with Covid-19 would be worse than those with myocarditis, and that it chose to model a high rate of myocarditis, meaning the condition may be less common.
In Pfizer’s briefing documents made available ahead of the meeting, the company cited data from Israel, where its vaccine is the main one in use and data on myocarditis have been closely tracked.
In these data, the risk of myocarditis after a second dose in 12- to 15-year-old boys was 1 in 12,000, Pfizer said, about half that in males aged 16 to 19. That’s based on 12 cases that occurred in 255,444 adolescents. Only one of those cases was in a female vaccine recipient.
Pfizer said in its documents that assuming the 90% efficacy figure on the vaccine holds up, vaccinating one million 5- to 12-year-old children would prevent 33,600 hospitalizations and 170 deaths over 120 days. During the same period of time, there would be 21 cases of myocarditis or pericarditis.
A draft agenda for Tuesday’s meeting shows that the committee will view presentations on myocarditis and other risks and on the benefits of the vaccine. According to the briefing documents, the panel will consider whether, based on the totality of scientific evidence, the benefits of the two-dose vaccine outweigh its risks for use in children 5-11 years of age.
If the FDA decides to authorize the vaccine, its use will then be evaluated by a separate panel convened by the Centers for Disease Control & Prevention. If that committee also recommends its use, and the CDC director agrees, the vaccine will be made available.
Damian Garde contributed to this article.