The Pfizer trial: what’s the news?
I’m going to start by talking through what Pfizer announced and how to think about its findings. Then I’ll do a few more specific FAQs.
The Pfizer announcement last week reported results from a trial of COVID vaccines in children. The trial has enrolled children as young as six months, but the announcement focused on children 5 to 11. Pfizer had data on 2,268 children in this 5-to-11 age group, and its press release indicates that it found evidence of both safety and efficacy. The company announced that it would apply by the end of the month for FDA Emergency Use Authorization (EUA) for this age group.
It is worth pausing on the question of why a different dosing trial was needed for children under 12; the vaccine was approved for 12-to-15-year-olds with the adult dose. The main answer is that because younger children are smaller and possibly more immune-responsive, they were likely to respond to a lower dose of the vaccine. (Stephane Bancel, the CEO of Moderna, explained this to me in an earlier newsletter.) This trial evaluated the vaccine in children 5 to 11 with a dose of 10 micrograms, a third the size of the 30-microgram dose given to older children and adults.
With this dose — it’s a two-dose regimen, three weeks apart — Pfizer says the vaccine was “well tolerated.” Side effects at this dose were comparable to the side effects for older people (some fatigue, fever, etc.). One very important thing to note is that when the FDA evaluates the Pfizer vaccine for EUA, it will delve much more deeply into the possibility of any safety issues. The agency will read in detail the medical data on every child in the trial to look for any possible concerns. So while Pfizer’s public statements on safety so far are simple, the detailed analysis of safety will be enormous.
Pfizer also argued the vaccine was effective, and here is where the data is interesting but also different from adult trials. In the adult COVID trials, the most important outcomes measured were COVID illness (serious illness, hospitalization, death). This outcome is not considered in the pediatric trials because it is too rare even among the unvaccinated group of children.
To see this in detail, think about the numbers. The trial is 2,268 children, of whom two-thirds got the vaccine (one third got a placebo). Even if every single one of the children in the placebo group got COVID during the trial, we would still expect only about 2.5 children to be hospitalized in that group, and no deaths. The actual infection risk is much lower, making these numbers smaller. If we are looking for significant reductions in risk from vaccination, we will not see them, because the baseline risk is so small.
This is very good news for worried parents! But it’s not good for the statistical analysis of that outcome.
To be what statisticians call “powered” to detect an effect on serious illness or hospitalization, we’d need a vastly larger trial. Which could be infeasible and would at a minimum delay vaccines even more. Instead, Pfizer is resting its efficacy claims on the antibody response to the vaccine. Which makes sense, since the way the vaccines work is they produce antibodies. When the company says the vaccine is effective, it means the antibody levels in children were comparable to 16-to-25-year-olds vaccinated with the adult vaccine (in fact, the kids had slightly higher antibodies, despite the lower dose).
So that’s kind of what we have at this point.
What happens now?
Pfizer will submit truckloads of paper to the FDA to read and will ask the FDA to approve the vaccine to be used under EUA. There was a mention of this happening “by Halloween,” but I’m finding the timing on these things very unpredictable in general. As soon as the FDA approval is through, vaccines can begin.
Let’s do some questions
There are many people out there, and I count myself among them, who are eager to vaccinate their kids. But there is also considerable hesitancy, even among adults who are themselves vaccinated (Aaron Carroll had a good recent piece on this). Children are very unlikely to get seriously ill with COVID-19, meaning the most significant impact of vaccines — preventing serious illness — is less important for them. Realizing that, more parents will be reluctant; we have seen it already, with adolescent vaccination rates lower than for older age groups.
As we move into facing these decisions for real, not just hypothetically, I hope we can be prepared to be a little bit gentle with each other. Asking questions about vaccines for kids or being more cautious for kids than older adults — these are reasonable approaches. If society dismisses anyone with any hesitancy as “crazy” and labels them an “anti-vaxxer,” I think we’ll get more anger and probably less vaccination.
So! I’m going to address a bunch of questions below that focus on what we know (and what we do not) about various vaccine concerns. I’m sure this will not be the last newsletter on these choices.
What do you see as the top reasons to vaccinate your child?
- To prevent them from getting COVID. Vaccines are excellent at preventing any COVID-19 infection. In the first months after vaccination, this protection among adults is close to 90%. Although it wanes some over time, we continue to expect significant protection against infection. Even if your child is unlikely to get seriously ill, we’d all prefer kids who are not sick.
- Also, if they get COVID, they have to stay home from school for 10 days. Or more!
- To prevent spread to older adults, who could still get seriously ill. Yes, even if they are vaccinated. It’s rare, but it happens, especially for the immune-compromised.
- To simplify or eliminate quarantine for exposure. Vaccinated exposures do not need to quarantine in many scenarios.
How can I be confident in vaccine safety with such a small sample size?
I think this is a good question. The fact is, with a sample size of about 2,300 kids, the trial is not going to pick up rare complications. Myocarditis, which does seem to be a risk in young men in particular after vaccination, is showing up at rates of a few in a million. Much more data would be needed to detect complications that are this rare. Of course, the flip side of that is that those complications are rare. Complications that happen to more children would be picked up.
However: we are not flying blind. At this point, millions of 12- and 13-year-olds have been vaccinated against COVID-19. Israel has already been vaccinating younger children. We are seeing that happen safely, and that kind of real-world data should inspire confidence.
As soon as FDA approval goes through, we’ll get even more data. Many people are very eager to vaccinate their kids, which means that within the first weeks we expect to see literally millions of children vaccinated. Nearly all adverse vaccine reactions are close in time to vaccination. For anxious parents who want to wait for more data, you will not have to wait long to see millions of observations.
My kid already had COVID. Do they need a vaccine? Two shots?
These natural-immunity questions are complicated. There are many serious people who think we have not paid enough attention to natural immunity and that we should use only one shot for those who already had COVID-19.
Previous COVID-19 infection confers protection. Based on adult data from Israel, even those who were previously infected had more protection against a breakthrough if they had at least one shot. This is a strong argument for vaccination with at least one shot for this young group.
I hope that the FDA and CDC will soon issue clearer guidance for both children and adults on how we should think about natural immunity (including discussion of boosters after breakthrough, etc.). But I’m staying tuned on this.
My kid is almost 12. Wait until 12 for an adult dose? What if they are small?
I’ve heard two versions of this. The first is: If my kid is almost 12, should I wait until they are 12 so they get the bigger dose? The second is: If my 12-year-old is small in size, should I try to get them the lower dose?
The answer to both is that it likely doesn’t matter. On the first: The lower dose is producing a lot of immunity. As your kid grows up further, they will surely be getting boosters at varying doses. If you’re eager to vaccinate, the best vaccine is the first one.
On the second: They did try adult doses on kids, and the main downside was slightly greater side effects like fatigue. So the risks of having the adult dose are minimal, and many small 12-year-olds have already gotten it. Again, the best vaccine is the first you can get.
What about kids under 5?
Kids under 5 were divided into two different groups in the Pfizer trials: 2 to 5 years, and six months to 2 years. The reason for the separate groups is the need to consider even smaller doses. The indication is the dose in these trials may be as small as 3 micrograms.
Results from these trials, which enrolled later, are expected at the end of the year. From there, the timeline will be similar. You may wish it were sooner, but if I were a betting woman I’d say we’d be vaccinating these groups in January.
The good news is that these groups are extremely low-risk for serious illness, and vaccination for their older siblings will provide protection from infection.
Will you vaccinate your kids?
Yes. There are a lot of reasons for this, some of them listed above. I do not want them to get COVID. I am worried about their immune-compromised grandparent. I would like to avoid quarantine and keep them in school. I’m confident in the vaccines and the FDA process.
So, yes. For Halloween I am hoping to dress my children as partially vaccinated. So far, my kids have expressed enthusiasm about the vaccine, but the costume idea is a tough sell.
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