Thread by @mlipsitch

Now out with @rebeccajk13 Interpreting vaccine efficacy trial results for infection and transmission authors.elsevier.com/sd/article/S02…
funded in part by #SeroNet

In which we show that earlier work by Rinta-Kokko et al on interpreting prevalence measures for vaccine efficacy generalizes to the COVID-19 case pubmed.ncbi.nlm.nih.gov/19490983/ and that the odds ratio for PCR+ in vax vs unvax persons swabbed at random

is under reasonable assumptions a lower bound on the vaccine's effect against transmission, the critical quantity for herd immunity that combines reduced risk of acquiring and shorter duration.

We further show that combined vaccine effect #VE measures using symptomatic + a proportion of asymptomatic cases have no clear interpretation, and swabs of _only_ asymptomatic don't either. Thus random x-section regardless of symptoms is the way to go.

Alternatively, testing the contacts of known cases can estimate VE against acquisition (VES in the parlance of @betzhallo @ilongini & C Struchiner), conditioned on infection, an approach taken in papers.ssrn.com/sol3/papers.cf… with @G_RegevY et al., in press in @LancetRH_Europe

As an example we take the data from the @moderna_tx vaccine RCT. Among asymptomatic persons at the second vaccine visit, the odds of PCR+ were 61% lower among vaccine recipients than placebo recipients. By the approach we advocate, this indicates one dose of Moderna vax

reduces one's ability to transmit the virus by >= 61%. We suggest it is probably considerably greater than 61% (apart from the statistical uncertainty in this estimate, which is substantial given small numbers) for 3 reasons.

1) only asymptomatics were swabbed, which tends to underestimate protection vs. swabbing all individuals; 2) a few individuals might have been infected before the vaccine was yet effective, and still shedding at the time of dose 2 (likely small effect);

3) doesn't account for any vaccine effect on the amount of shedding, which other studies show is substantial and likely further reduces transmission risk.

Much more work needed to quantify transmission effects but this is good news, esp. for one dose.

Next preprint in this line of work looks at viral shedding as an outcome medrxiv.org/content/10.110… with @LeeKShaffer joining @rebeccajk13 and me -- still under peer review