Tuesday, March 16, 2021

Vaccine nuance

This is Joseph.

Are all covid-19 vaccines precisely equal? No. Should you care very much which one you get? Also no. This seems like a contradiction until we think it through. 

Prior to the reporting of any phase 3 trials, the pre-specified efficacy for a useful vaccine was often cited as 50%. Here is an NPR story discussing this prior to Pfizer results. It is worth noting, as Bill Miller states, that even a weak vaccine likely reduces severity:

"That's certainly the case with the influenza vaccine," Miller adds. "People who get the vaccine may still get the flu, but, for the most part, their disease is milder than if they hadn't had the vaccine."

So how do the US vaccines stack up to this standard? For the trial endpoints, Pfizer is 95%, Moderna is 94%, and Johnson and Johnson is 72%. Even the lowest efficacy vaccine is almost exactly at the 75% Dr. Fauci pre-specified as what he was hoping for, even if he was unsure it was realistic.  Further, there are other trade-offs between the vaccines, including price, storage requirements, or number of doses. The lower efficacy option has better storage properties, is cheaper and is only a single dose. The newer vaccines that might yet be approved also look good, AstraZeneca is 70% and Novavax is 89%, so there are a growing number of options far more effective than the pre-specified level needed for a useful vaccine. 

Based on this, there are only safe and effective options available in the United States. I suppose that there might be some customer preferences, but everything is safe and works, based on the trial data. 

So what can real world evidence add? 

Well, we can try to find rare side effects. There was some concern about the AstraZeneca vaccine (not available in the US) and blood clots, at least until people noticed that the rate was lower than would be expected by chance. One of the sanest voices in the pandemic points out that this might be lower than by chance:

Professor Sir David Spiegelhalter, a statistician from the University of Cambridge, urged caution over the decision to pause the AstraZeneca vaccine rollout in some countries, saying it could be doing "more harm than good".

But it is important to monitor for problems. For example, if there were big ones with the Pfizer vaccine then you'd expect Israel to have noticed by now. Spoiler: there weren't any.

We can also measure the population level effects on disease. So we know that the AstraZeneca (AZ) vaccine appears to reduce population rates of hospitalization by 95%, which was higher than that seen post-vaccination by Pfizer, at 84% (this was based on 1.14 million vaccinations in Scotland) -- although this was mostly comparing single dose Pfizer to single dose AZ (results could differ after 2 doses). Both vaccines are mitigating the human cost of the pandemic, which is the reason the pandemic was a crisis to begin with. 

So how does this all link together? All of the evidence suggests all of the vaccines are good. Scotland's real world evidence muddies the waters as to the precise rank ordering (as it is unlikely that the populations being vaccinated were terribly different) but that doesn't change the underlying message: none of the vaccines is showing concerns as to safety or efficacy. I would gladly be randomized to any of the three US available options or to AZ. Even if it was done with a biased die. 

Finally, if I did have to do any sort of prioritization then I would do it via focusing on high risk populations. Give the mRNA vaccines to older and minority groups, who suffer more from the disease. Focus the adenovirus vaccines on the young and high SES crowd. That said, vaccines in arms is the most important variable and every person vaccinated does make the community, as a whole, safer. 

Looking at Mar 15 data, you would rather be the US (21% with 1+ dose), Israel (57% with 1+ dose), or the UK (37% with 1+ dose) and not somebody like Canada (4.7% with 1+ dose). And the number of doses given is vastly more important than the type of vaccine used, provided it is one of the five above with extensively reported phase three clinical trial data. 

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