4 ms·

>There's not just one figure of merit. The most important one is the ratio between (month 1 to month 2 efficacy) with the delayed dose vs. with the on-time dose

by yyyk 6y ago

>There's not just one figure of merit. The most important one is the ratio between (month 1 to month 2 efficacy) with the delayed dose vs. with the on-time dose. If that's 0.5 or more, it's a slam dunk: you delay. 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. ]

mlyle 6y ago
> 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. 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.
- yyyk 6y ago
  Sorry I misunderstood. Your original phrasing implied a case when the protection increases (If month 1 / month 2 = 0.5 then month 2 is twice month 1). 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.
  - mlyle 6y ago
    The original RCT doesn't measure the exact same thing, which is why we need to actually try to measure it and confirm protection is durable... 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).
    - yyyk 6y ago
      >But one would expect that protection from days 21-41 without a second dose is comparable to protection from days 14-21. 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? [0] https://www.researchsquare.com/article/rs-226857/v1 https://www.researchsquare.com/article/rs-226857/v1
      - mlyle 6y ago
        > First, There's a study I linked to earlier, suggesting the 1st dose antibodies aren't good against the variants. 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%).

by yyyk 6y ago

mlyle 6y ago

> 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. 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.

yyyk 6y ago
Sorry I misunderstood. Your original phrasing implied a case when the protection increases (If month 1 / month 2 = 0.5 then month 2 is twice month 1). 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.
- mlyle 6y ago
  The original RCT doesn't measure the exact same thing, which is why we need to actually try to measure it and confirm protection is durable... 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).
  - yyyk 6y ago
    >But one would expect that protection from days 21-41 without a second dose is comparable to protection from days 14-21. 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? [0] https://www.researchsquare.com/article/rs-226857/v1 https://www.researchsquare.com/article/rs-226857/v1
    - mlyle 6y ago
      > First, There's a study I linked to earlier, suggesting the 1st dose antibodies aren't good against the variants. 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%).