A few tweets on a topic that keeps coming up in discussion. There are many different types of vaccine efficacy - efficacy against infection, against transmission, against disease, and against severe disease - and these can vary for a single vaccine. How are they related? 1/5
Efficacy against infection will by necessity be lowest, because if a vaccine protects you from infection, it also protects you from transmitting to others and getting symptoms. We have a little data on this from Moderna and Oxford, but will get more from antibody testing. 2/5
Even if a vaccine does not prevent infection, it could make you less infectious by reducing viral load, reducing duration of infectiousness, or by preventing symptoms like coughing/sneezing. This effect is hard to measure without contact tracing or cluster randomized studies. 3/5
Even if a vaccine does not prevent infection, it can still prime your immune system so that you don't develop symptoms, particularly severe symptoms. In general, vaccines work best against severe disease. Though we have less data here, we see this trend for COVID vaccines. 4/5
So while we think about vaccines as having 70% efficacy of 95% efficacy, this almost always refers to the ability of the vaccine to prevent symptomatic disease of any severity. It will take time to generate reliable estimates of the other types of efficacy. 5/5

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More from @nataliexdean

29 Dec 20
Our group's household secondary attack rate meta-analysis has gained traction, but not for the reasons I'd hoped for. We did not conclude "no asymptomatic or pre-symptomatic spread" of SARS-CoV-2. A short explanation of what we did observe. 1/7
Using only the household studies included in our main analysis, we conducted a sub-analysis breaking out index cases designated as symptomatic versus asymptomatic/pre-symptomatic. We observe lower transmission from this latter group, though there was much less data. 2/7
Since we are relying upon other studies in the literature, we were unable to separate out fully asymptomatic index cases (never develop symptoms) from pre-symptomatic index cases. But others have tackled this problem directly. Their conclusions below. 3/7
Read 7 tweets
22 Dec 20
As @hankgreen nicely points out, we have to be careful that "we don't know whether the vaccine reduces transmission" doesn't morph into "the vaccine doesn't reduce transmission." How do we communicate this uncertainty? A few thoughts. 1/7
First, vaccine efficacy against infection can't be higher than vaccine efficacy against disease. If something prevents infection, it also prevents disease. But vaccines can work by preventing symptoms, and so give an extra boost to efficacy against disease. 2/7
So while we expect vaccine efficacy against infection to be lower, we aren't sure how much. We have a bit of data from the UK/Oxford and Moderna trials showing reduced infection, but we are waiting on antibody testing data from these and other trials. 3/7
Read 7 tweets
8 Dec 20
Out in @TheLancet, results from the Oxford/AZN trials, including more detail on the low dose results. Notably, the low dose recipients "received their second dose after a substantial gap." Only 0.8% received a second dose within 8 weeks of the first. 1/5
Recall that the low dose results were only from adults 18-55, only during a short time window, and only in the UK. Per reviewer request, they restricted the standard dose analysis to a similar group. We still see separation (middle rows), but with more uncertainty. 2/5
Overall, the 62% result for the standard dose regimen appears robust, and meets pre-specified criteria (>50%). But I am still not sure what to make of the low dose result. Is it the longer gap between doses? The low dose? Both? And there remains no data for older adults. 3/5
Read 6 tweets
25 Nov 20
With respect to the AstraZeneca vaccine, I am guessing people think my objection is to science by press release, and that I want a peer-reviewed publication. But no, not really. What I want is reliable and definitive evidence to inform policies impacting millions. 1/4
If the answer is that AstraZeneca needs to go back and add a new half-dose arm to their trials so that they can prospectively evaluate its efficacy in diverse subgroups, then we have to carefully consider the value of a peer-reviewed publication at this moment. 2/4
We’ve written about this in @NEJM. Basically, there are risks to publishing results that are “promising but inconclusive.” Though it seems slower at the time, in the long run it is better to generate the conclusive evidence while we still can. 3/4
Read 4 tweets
24 Nov 20
Astrazeneca/Oxford get a poor grade for transparency and rigor when it comes to the vaccine trial results they have reported. This is not like Pfizer or Moderna where we had the protocols in advance and a pre-specified primary analysis was reported. 1/5
AZN is evaluating their vaccine in multiple trials across the world, yet these are not embedded under a unified protocol. In fact, the trials seem to be quite different by country, in terms of populations, subgroups, etc. Based on the publicly available details I've seen. 2/5
With the exception of the US-based trial, I am not aware of details on how these trials are being monitored. Is there a centralized DSMB? Are they combining the accrued data? They seem to have combined events across Brazil and UK. Why not the other countries? 3/5
Read 5 tweets
23 Nov 20
A short thread on vaccine efficacy versus vaccine effectiveness, covering:
- Idealized vs. real-world effects
- Direct vs. indirect effects
- Individual-level vs. population-level effects
- Phase III vs. Phase IV trials
Phase 3 trials are conducted under idealized conditions. Everyone receives all doses on time, that have been properly stored, etc. The primary analysis is restricted, like to people without antibodies at baseline. We call the resulting estimate "vaccine efficacy." 2/8
Think "vaccine efficacy" as our best guess at the biological protection of the vaccine. When we talk about "vaccine effectiveness," this can refer to a few different things. One is "real-world effectiveness." If conditions are less than ideal, how well does the vaccine work? 3/8
Read 8 tweets

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