Saturday, December 12, 2020

Combining Experimental Vaccines + Variolation

Current estimates suggest that the US will end up with around 500k Covid deaths (itself but a tiny fraction of the total harm done), with eventual herd immunity reached half via vaccination and half via natural infection.  I expect we could've done much better via variolation (low-dose viral inoculation), for reasons I've previously discussed.  But I've recently learned that an even better option was available -- though it's not one that I've seen anyone suggest before.

NY Mag reports that "We Had the COVID-19 Vaccine the Whole Time" (well, since February).  Many now wonder: Would it have been prudent to distribute the experimental vaccine, at least to high-exposure or high-risk individuals, even before it was proven safe and effective?  Quite possibly.  After all, the risks from an untested vaccine of this sort are much lower than the risks from COVID-19 for many individuals.  The main potential downside would be the "moral hazard" of vaccinated individuals behaving more recklessly and spreading COVID if the vaccine turned out to be either (i) ineffective, or (ii) effective only at suppressing symptoms but not viral transmission.

But this risk could in turn be avoided by a combination policy of vaccination followed by variolation (with quarantine).  If the vaccine fails, variolation acts as a "fail-safe" to provide natural immunity (while minimizing unwitting community transmission, in stark contrast to all our uncontrolled infections).  And if the vaccine worked (as turns out to actually be the case) then the risks from variolation are further minimized.  Given even a moderate chance of vaccine effectiveness, the expected value of variolation is significantly bolstered (due to reduced risk).

(As a bonus, such a policy would serve as a kind of large-scale "challenge trial" of the experimental vaccine's effectiveness.  Once proven safe and effective, one could drop the variolation and switch to a vaccine-only policy -- many months sooner than would normally be possible.)

It would be interesting get a sense of what expert expectations regarding the vaccine were (prior to the trials being carried out).  My sense is that there's some surprise at just how effective it proved in trials, but not surprise that it was effective to at least some degree.  So I suspect that most reasonable probability assignments, given what was known at the time (by mid-March, say), would imply better health outcomes, in expectation, from this combination policy compared to our actual outcome. That could be denied.  But when one further factors in the immense indirect harms of the ongoing pandemic, it seems almost undeniable that this proposal would have had (very!) positive overall expected value in comparison.

I wonder if, upon careful reflection, anyone could honestly disagree with this?  Many would oppose the idea on a knee-jerk basis, of course, or because they can imagine one possible way that it could've turned out (slightly?) worse than our actual outcome (and so it sounds "reckless" to those who suffer from status quo bias).  But does anyone think that a reasonable assignment of probabilities and values would lead to this policy having lower value, in expectation, than we're now stuck with in our actual outcome?  If so, I'd be very curious to hear the details...


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