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Yes, let’s vaccinate twice as many people against covid-19

I am very sympathetic to Robert Waldmann’s argument that we should give twice as many people one dose of the new Pfizer/Moderna vaccines, at least until supply constraints are eased, instead of following the FDA approved vaccination protocol and giving everyone two doses right from the beginning. What follows is a rough way of thinking about the logic and perhaps the magnitudes involved. Let me emphasize that this is just a finger exercise and I am not an epidemiologist, but with those important caveats I will share my work.

Here are my assumptions. The reproduction number of the virus is currently 1. This means that if behavior, transmissibility, and natural and vaccine acquired immunity are all unchanged, the number of people getting infected each day will remain the same. I assume that there are 300 million people in the United States, 40 million of whom are currently immune due to prior infection, and 260 of whom are susceptible. There are 400,000 new actual infections each day (two times the reported number of cases). These infections lead to 3,000 deaths per day (roughly the current number).

Liveblogging the FDA hearing on the Moderna Covid 19 vaccine

So Far the efficacy data has been presented. As reported in the press earlier, the vaccine is roughly 95% effective, that is roughly 95% of people who got Covid 19 during the trial were participants who received the placebo.

Importantly, the null hypothesis that just one dose is just as good as two was not rejected. The test of this null had extremely low power as almost all participants received both doses, so basically this means cases less than 4 weeks after the first dose (so one week after the second dose). However, note the extreme rigidity of the FDA.

Before allowing vaccination, the FDA required proof of efficacy. Before allowing a modification from two doses 4 3 weeks apart to one dose, the FDA requires … I don’t know maybe if Jesus Christ returned and petitioned them for some flexibility, they would give Him a hearing, but I guess they would tell him he needed to propose (and fund) a new Phase III trial.

update: incorrect assertion of fact crossed out

It is also true that there is no evidence of benefit from the second dose of Pfizer’s vaccine. It is clear that people who have received one dose of either vaccine are among those least at risk of Covid 19.

See the raw data below from Polack et all 2020 . Can anyone see from the Kaplan Meier plot when the second dose was given ?

The vaccines are in very short supply. People are anxiously waiting for vaccination. Because the protocol had two doses, half of the vaccine will be reserved for the people who will benefit least.

Here there is a difference between careful science and optimal policy. In science it is crucial to write the protocol first then follow it mechanically. This is necessary so that the experimental interventions are exogenous and one can be sure they cause the observed outcomes and are not caused by observations.

However, it is not optimal policy to reduce the possible decisions to two, a priori with extremely limited data. This is what the FDA does. I think they should approve a single dose. Their rule is always to only act on extremely firm knowledge. It is, in this case, not going to be first do no harm. The second dose has side effects (mild but not zero). There is, I think, no weak evidence of benefits. (Again, the test has extremely low power (and I’m not sure protocol did not say the question would be addressed — if it didn’t then there is a problem — the rule decide what to do in advance applies to data analysis too — it is vital that the data not be dredged looking for a significant coefficient)). I think the point estimate is pretty much exactly zero benefit. of a benefit of the second dose much lower than of the first (and without proof of any benefit.

I think that people should be given a single dose. After everyone who wants one dose has been vaccinated, then it makes sense to give people a second dose. There is no reason to think spacing 4 3 weeks apart is optimal — the spacing was decided in advance (and it was 4 weeks for the Moderna vaccine hence my mistake).