The FDA initially wanted 2 months of data for under 12, just like adults. Then they changed their minds and wanted 6 months instead. I'm sure they had a reason, but in 70 years of vaccines, we've never had a side effect after 2 months. If they changed their minds once, they can damn well do it again and get this thing out there.

Then there's the objections (and resignations) to the booster. The specific reasons being:

> current vaccine supplies could save more lives if used in previously unvaccinated populations than if used as boosters in vaccinated populations

We all know this, but it's not the FDA's job to factor in global supply and distribution. Are boosters safe and effective? That's the FDA's job. Will denying boosters in the US increase first shots in other countries? That sure seems debatable to me. But regardless, it's not the concern of the FDA. I don't know what the hell they have been doing, but they've been going far beyond their scope lately.

How are they going to model efficacy if child mortality is very low already?

I think the first efficacy data is going to be about preventing infections. Data about preventing deaths will take longer to obtain.

Infections in a world where asymptotic spread is possible seems tough to measure. Are infections measured by symptoms such as cough, fever, etc, or by enough virus replication to shed or expel viral enough material to infect others?

Depends on the study design. Infections are detected by doing a PCR covid test. However, different studies might have different criteria for exactly who gets tested.

PCR doesn’t differentiate between live and dead virus molecules, which makes it less than diagnostic for active infection without symptoms, right?

That distinction isn't as important for evaluating vaccine efficacy. It wants to measure if the person was infected, not if the person is infectious.

If a trial subject is exposed to virus and the vaccine works to trigger an effective immune response, how does PCR know the difference between virus molecules neutralized by vaccine response and those neutralized otherwise?

In those cases the virus particles don't replicate enough to be detected.

How is a difference be determined between between vaccine enhanced immune response, normal immune response and not exposed?

The basic structure of a phase 3 vaccine efficacy trial is that you give the vaccine to half of the volunteers and placebo to the other half. Then you you wait for them to naturally be exposed to COVID. When a pre-determined number of infections is reached, the data is unblinded and they compare how many infections happened in the vaccine group vs the placebo group. If less people are infected in the vaccinated group then it shows that the vaccine is effective.

The initial comment wrote:

The FDA initially wanted 2 months of data for under 12, just like adults. Then they changed their minds and wanted 6 months instead. I'm sure they had a reason, but in 70 years of vaccines, we've never had a side effect after 2 months. If they changed their minds once, they can damn well do it again and get this thing out there.

If child mortality and clinically significant infection are low, then would it not potentially take longer to see a statistically difference in a difference between vaccine and placebo subjects?

I believe part of the difficulty was the lull in infections before delta, plus the effectiveness of school closures. If nobody is getting sick, you cannot say anything about effectiveness.

I don’t know if they want proof of effectiveness again, or are specifically looking at risk (which would not be impacted by the above).

If guess the risk of death is so low among children, you need far more data to exclude a risk from vaccination at that (small) magnitude. Think of helmets, and how they are exactly as comfortable to wear in a car as they are on a motorcycle.

> I'm sure they had a reason, but in 70 years of vaccines, we've never had a side effect after 2 months.

Have we ever had mRNA vaccines?

no, but nothing about the mechanism of mRNA vaccines suggests they'd be an exception in that regard, since mRNA is very short-lived and thus if you'd get long-term effects, you'd have them from other delivery methods too.

As Vinay Prasad would say, It is often our mechanistic understanding that misaligns with study results. All we can do is test.