As for your link, according to the original PDF[0] this is raw data before any statistical corrections, which makes it not very useful. The person you're quoting has been noted as a relative pessimist, assumes that 1st dose effect is very small due to behavioural changes[1], and that a lot of the effect is due to the lockdown. (IMHO, he's too pessimistic, but again I'm far from an expert).
[0] https://kinstitute.org.il/wp-content/uploads/2021/02/covid_1...
[1] https://twitter.com/KalksteinNir/status/1358735186637299715
RCT > CCT > Time series.
So we've got RCTs for each Pfizer and Moderna that show similar first dose efficacy. We've got prelim CCT data that seems to show Pfizer efficacy but a bit lower than we'd like, confounded by possible behavioral changes. And we have time series data that seems to show first dose efficacy.
And then we have the very-confused-seeming over-tweaked analysis of time series data that you keep linking, too, comparing to base population rates without any effort at case control, which shows negative efficacy.
Anecdote: the people that I know who received their first dose decidedly did not become less active, either in the near term (actuality: slightly more active) or the longer term (actuality: considerably more active).
IMHO, Judging by what happened in Israel at the time (a rise in cases), I for one wouldn't recommend a one dose regimen. So I don't consider what I'm saying supported by only one analysis, but by all of the Israeli CCTs so far. Judging by the consensus of Israeli HMOs, they probably feel the same.
[EDIT: Basically, I don't consider a low efficiency all that different from '1st dose isn't efficient'. So we give people the 1st dose, they party, and we come up even.]
* Yes, people probably became more active, but remember there was a lockdown too, and a different variant than in the original RCTs. There's justification for a lowered efficiency beyond bias in the RCT.
There's not just one figure of merit. The most important one is the ratio between (efficacy during the second month) with the delayed dose vs. with the on-time dose. If that's 0.5 or more, it's a slam dunk: you delay.
But post-dose 2 efficacy and immune titers and side effect profile matter, too. It's likely the long term efficacy is higher with delayed dose 2. This is what we see in most vaccines and 21 days is very, very early for a booster.
> remember there was a lockdown too,
Lockdown shouldn't affect anything in the CCT data. It's case controlled?? Presumably lockdown affects people in the two groups similarly, unless you're suggesting it reduces activity more in people who are vaccinated somehow..
So you're suggesting people with 1st dose keeping increasing the protection despite no booster in the delayed dose scenario. Possible, but important to point out that's not supported by the original RCT which takes no position on the matter.
>This is what we see in most vaccines and 21 days is very, very early for a booster.
True, but MRNA vaccines are new. 21 to 28 days could be the right period there.
>Presumably lockdown affects people in the two groups similarly, unless you're suggesting it reduces activity more in people who are vaccinated somehow..
No, but it dampens the 'people who get vaccine are partying' effect. I'm suggesting lockdown could prevent an effect you'd be seeing in the real world if we did this with no lockdown.
[EDIT: I'll respond to your other post here since this thread is already too sprawling.
>The only CCT preliminary data that I've seen suggests that one dose is protective. You have more CCTs?
My argument is that a low enough protection isn't so different from no protection. Lets say we give a delayed shot, people party for a longer time, the end result balances itself or could even be negative. ]
No?
I'm suggesting we compare e.g. cases from day 21 to 42, when A) second dose is given on day 21, and B) second dose is given on day 42. (And people are blinded).
If efficacy B is at least half of efficacy A, then it makes sense to follow plan B.
Anyhow, it's important to note that the original RCT takes no position on what the result [month 1 / month 2] would be. It's a worthy thing to check, but it's not supported by the RCTs or CCTs.
But one would expect that protection from days 21-41 without a second dose is comparable to protection from days 14-21.
We do also have some indication of durability of a single dose from the phase 2 safety trials (looking at titers).
I'm not sure that's enough for two reasons.
First, There's a study I linked to earlier, suggesting the 1st dose antibodies aren't good against the variants[0]. That would mean we need the booster ASAP.
Second, if the original efficiency is low, we're putting people at risk longer even if it stays about the same in 21-41. Imagine the 33% figure is correct. I don't think FDA would have approved the vaccine if efficiency < 50%, so should we keep people with such a low protection for another 20 days?
It suggested the neutralization titers were worse, not that they were ineffective.
> so should we keep people with such a low protection for another 20 days?
We compare the ratio between people delayed and not delayed.
If a delayed person keeps, say, 50% efficacy, and the person with the second dose has 95% efficacy, giving two people 50% efficacy is better than giving one person 95% efficacy. That's why I suggested the specific figure of merit that I did.
(That is, imagine you produce 1 dose per 21 days, and there's two people in the world. You could give, in successive 21 day periods:
A 50% protection, B 50% protection, A 95% protection, B 95% protection.... (population efficacy 25%, 50%, 72.5%, 95%)
or you could give A 50% protection, A 95% protection, B 50% protection, C 95% protection). (population efficacy 25%, 47.5%, 72.5%, 95%).
See figure B here taken from the study. That's a large difference to my completely untrained eye.
https://twitter.com/AArgoetti/status/1359994177409478656
>If a delayed person keeps, say, 50% efficacy, and the person with the second dose has 95% efficacy, giving two people 50% efficacy is better than giving one person 95% efficacy.
That logic breaks down when the divided efficacy is too low, even if it's formally half of the original. Say efficiency is 33% (and lets pretend the original is 66%). The people who got the 33% efficient vaccine go out and party, balancing out the effect. People think the vaccine doesn't help. Eventually nobody trusts your vaccine, and nobody shows up to get the second dose. I'm not sure 50% is high enough. Maybe it is, but just barely.
So, LoQ means limit of quantification, aka the threshold below which things can't be measured in their assay technique. I know it's a log scale, but...
The study was barely able to detect the response to the baseline variant, so it doesn't take all that much of a drop to escape the study's quantification limit.
It's extremely misleading to plot the line all the way down to the bottom of the graph, when all you know is that it is (probably) less than the LoQ line. I say "probably" because this assumes the authors have accurately determined the LoQ, which is easy to mess up.
> That logic breaks down when the divided efficacy is too low, even if it's formally half of the original. Say efficiency is 33% (and lets pretend the original is 66%). The people who got the 33% efficient vaccine go out and party, balancing out the effect. People think the vaccine doesn't help. Eventually nobody trusts your vaccine, and nobody shows up to get the second dose. I'm not sure even 50% is high enough
I disagree.
In any case, it's 2:56AM. I'm going to sleep :P
I'm a bit confused by what this means.
> So I don't consider what I'm saying supported by only one analysis, but by all of the Israeli CCTs so far.
The only CCT preliminary data that I've seen suggests that one dose is protective. You have more CCTs?
Your assertions are hard to reconcile with e.g. https://pbs.twimg.com/media/Et4moRCXAAAZ18o?format=jpg&name=...
Note that most of the people positive at 21-27 days would have been exposed before the 2nd dose... Yes, it's crappy time series data, but...