Breaking: Pfizer vaccine data for children 5-11 released.

Lower doses generated similar antibody responses. Whew.

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Finally. We finally have some data on the safety and benefit of Pfizer’s coronavirus vaccine for children ages 5-11. After months of waiting, including delays resulting from an expansion of the trials requested by the US Food and Drug Administration starting in July, we have important answers. But also, many unanswered questions.

The mRNA vaccine, which has shown high effectiveness among adults and adolescents ages 12 and up even in the face of the Delta variant, appears to stimulate robust antibody production in younger children. While no specific safety data were provided in the press release from Pfizer and BioNtech (the biotechnology company that partnered with Pfizer in developing the vaccine) what little we were given seems to be loaded with hints about the safety and possible protection the two-jab series offers.

Screenshot from today's press release from Pfizer and BioNtech.

According to Dr. Ugar Sahin, the co-founder of BioNtech, “The safety profile and immunogenicity data in children aged 5 to 11 years vaccinated at a lower dose are consistent with those we have observed with our vaccine in other older populations at a higher dose."

There’s a lot there. Let’s dissect some key phrases.

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“safety profile...at a lower dose” seems almost to imply that the safety profile at higher doses did not closely match the safety profile seen in older populations, such as adolescents and young adults. And perhaps this is precisely why Pfizer chose the lowest of the three originally tested doses for children ages 5-11. There has been a lot of speculation, including by me, around why Pfizer and Moderna were asked to expand their pediatric trials this summer. The fact that Pfizer ultimately selected the smallest of the 3 proposed doses for this age group and that the safety profile was found to be similar to that seen in older populations is vital information. It implies that the higher doses, which were 2 and 3 times more concentrated, might have elicited many more serious adverse events, events which could have derailed vaccine confidence if we’d started to vaccinate thousands of children and cases of myocarditis (a known but unusual side effect in children and young adult males in particular) started popping up early and a little too often for comfort. On the other hand, if the low dose had turned out not to provide enough of an immunity punch, the trial would have been a failure as well. So just how well did the low dose perform in terms of kickstarting antibody production?

“Immunogenicity data” data is all we’ve been given so far. This specifically refers to antibody levels, not any clinical outcomes, unfortunately. The good news is that the low dose was found to have stimulated antibody levels on par with those generated by three times the dose administered in older populations. It is hoped that since these levels replicate ones detected in older populations in whom clinical outcomes are already known from earlier studies, the vaccines will offer the same clinical protection. This extrapolation is known as “immune-bridging.” While the lack of direct clinical information is disappointing, it’s not entirely surprising. This trial mainly sought to evaluate safety (the frequency of adverse events) and antibody levels. Given how unusual—and yet not unheard of—serious Covid-19 illnesses are in children, the study was correctly conceived, as Dr. Angela Rasmussen and I wrote in The New York Times back in March. So while the data we were given today are “surrogate measures,” the results taught us something important: the lowest considered dose generated similarly robust antibody levels, implying a protective effect was provided. This makes having waited for these data, rather than pressing ahead without safety or immunologic information, wise.

That brings us to “…consistent with those we have observed with our vaccine in other older populations at a higher dose.” This feels ever-so-slightly like a dodge to me. In my view, Pfizer set itself up for a bit of a womp-womp moment here by having previously highlighted that it had found its vaccine demonstrated 100% clinical efficacy among teens back in March. Bragging about that finding always struck me as an interesting choice. On one hand, 100% sounded great. But it also meant that the results could only go down from there. Maybe that’s what Pfizer “wanted,” though: to set up the narrative for boosters down the line. Nevertheless, it’s interesting that this quotation essentially implies the immune-bridging concept while omitting actual clinical data. It’s possible that there were simply too few cases to report on. It’s also possible that given the Delta variant, the vaccine efficacy in preventing symptomatic Covid-19 or asymptomatic infections (both of which the trials are tracking as “secondary outcomes”) was found to be far lower than 100%. Even if the real number were as low as 40-50% in preventing infection, however, that would not be an abject failure. We would do well to remind ourselves that the vaccines were primarily designed to prevent severe illness. With Delta breaking through among vaccinated people more frequently than previous variants—but still keeping most people out of the hospital—the original aim to use vaccines to lower the hospitalizations and fatalities appears both wiser and more attainable focusing on infections.

•••

Before today, many people urged the FDA to skip its normal processes. Do today’s results vindicate them?

No. They merely guessed right. If they had guessed wrong, the consequences would have been disastrous. For pundits who can’t comprehend the burden of decision-making, the consequences of both action and inaction, it’s all too easy to imagine that these choices are straightforward, and that seemingly long waits reflect lollygagging.

They just don’t get it.

While opening the floodgates may get a few eager people vaccinated sooner, if anything went wrong...it would turn off droves of hesitant people.

The FDA and the CDC panels must be permitted to do their work free from political or public pressure. Safety mechanisms are not for obvious situations, but for non-obvious ones. Non-obvious problems can be serious and they are just the ones that people joining this program already in progress are not likely to consider. The detection of rare but important adverse events require professional assessment. Rigorous assessments of large and reliable datasets evade the real problem of “what I can’t see, I don’t know,” or worse, “what I can’t see, can’t truly exist, nor can it be a real problem.” That’s a naïveté we just can’t afford.

I am convinced that if we let our guard down on the safety checks, we will end up with fewer vaccinated people in the end. While opening the floodgates may get a few eager people vaccinated sooner, if anything went wrong, say more vaccine-driven side effects than Covid-19 hospitalizations in young kids, it would turn off droves of hesitant people.

The delayed gratification in waiting for good trial data can be tiring. But it’s worth it because it is likely to save more lives in the end by reassuring the hesitant while permitting scientists to refine our understanding of what doses are safe and most effective for every population. We won’t get to study this ever again. We have to get it right the first time.

Do today’s data give you what you need to know? Leave a comment!

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