Why we should be optimistic about various vaccines

I’ve been a long-time reader of your blog, and I have enjoyed your analyses of how the pandemic could play out in the US.

I saw that you gave some space to Arnold Kling’s pessimistic take on the vaccines. I’m a volunteer in the J&J Phase 3 vaccine trial, and my experience of the trial design makes me more optimistic about the vaccines than even the headline numbers in the so-far announced trials would suggest. I think the trial set-ups particularly for J&J have some biases that would lead to understated effectiveness results:

First, these trials are effectively unblinded. The placebos are saline solution in J&J, AstraZeneca, Pfizer and Moderna. Per the Phase 2 results for J&J, >60% of participants had significant side effects, with flu-like symptoms the most common; I believe other vaccine trials had similarly intense side effects. When I got a shot, I was nearly bedridden for 24 hours; it felt as if I had the flu, and the effect was far more pronounced than for any other vaccine I’ve had. If I got the placebo, I need a psychotherapist. Though I plan to remain generally responsible and not take too many incremental risks, given I’m only mostly sure I got a vaccine that is still unproven, I’m sure my assumption that I’ve been vaccinated will influence my behavior, and the behavior of anyone else who has had significant side effects from their injection too.

Second, upcoming trials are likely going to suffer from a “too much COVID effect” on an absolute basis, and relative to prior trials in particular. J&J counts any infection more than 14 days after injection toward its efficacy calculation. If full immunity takes longer (and my understanding is that antibodies build after infections for 3+ weeks in many cases), then there will be people out there getting infected before the vaccine has taken full effect. That wasn’t particularly likely to happen in the summer when there were fewer cases overall. This is particularly going to affect 1-shot vaccines, as other trials have their effectiveness measured only after the second dose (but I could still imagine this dynamic having some impact, if full immunity builds gradually after the second dose).

Anyway, hope this is of some interest. I found it encouraging to conclude that study bias could understate, not overstate, the effectiveness of vaccines.

That is from my email, identity of the author is redacted.


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