Pfizer's Covid Vaccine for Young Kids Is a Mess. Here's How They Screwed Up.

[Geee]

Real Clear Science

The FDA’s decision last week to postpone its evaluation of the Pfizer Covid-19 vaccine for children aged 6 months to 4 years old caught most observers off guard. After all, when an organization like the FDA asks a pharmaceutical company like Pfizer to file for an Emergency Use Authorization, despite the clinical data not yet being all in, the assumption is that they are planning to approve it. That assumption proved to be incorrect.

Instead, the FDA announced last Friday that an advisory committee meeting scheduled for this week would be postponed to April. It was a weird conclusion to a weird two months for this vaccine, and one worthy of some introspection on the part of both Pfizer and the FDA. With the benefit of hindsight, it seems pretty clear that Pfizer guessed low on the proper dose for this age group. Not so clear is how best to clean up the air of confusion around their vaccine product now. 

Clean it up they must, however, because confidence in our institutions is paramount in this era of unprecedented scrutiny and suspicion of vaccines. I have some thoughts on the matter; unfortunately, I fear they would be deemed inconvenient by both Pfizer and the FDA.

Building a Better Immuno-Bridge

First off, I do not want to pretend that the decision tree behind trial design for a new vaccine technology is straightforward. I am not a vaccinologist nor an immunologist, but I can only imagine that variables are many and stakes are high. In this case, Pfizer needed to pick a dose for young children, with the reference that adults and adolescents did quite well in clinical trials with two 30 microgram (mcg) doses separated by 3 weeks; as did children ages 5 to 11 with 10mcg doses. Reasonably enough, when it came time for the trial, Pfizer opted again to trial a dose a third of that used in the older group (3mcg) as well as the 10mcg dose used in older children.

Before running the full trial with about 2500 children, Pfizer tested these doses on a couple dozen kids in their Phase 1 trial. The 10mcg dose caused a fever, sometimes severe, in about 20% of the small number of children in the Phase 1 trial (a similar, but far more pronounced, effect occurred in the trial for children age 5-11 when a 30mcg dose was tried - everyone ended up with a fever!). This led to abandoning the 10mcg dose before the Phase 2 and 3 trials. Thankfully, everything looked fine for the 3cg dose from the Phase 1 data; note the equal titres for both age groups on the left, and how they are actually higher than the age 16-25 on the right:

[Valin]

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