2 ms·

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,

by 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%).
    - yyyk 6y ago
      >It suggested the neutralization titers were higher, not that they were ineffective. See figure B here taken from the study. That's a large difference to my completely untrained eye. https://twitter.com/AArgoetti/status/1359994177409478656 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.
      - mlyle 6y ago
        > See figure B here taken from the study. That's a large difference to my completely untrained eye. 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
        yyyk 6y ago
        C'ya around. You'll make a fine educator - sure taught me a few things this time.
mlyle 6y ago
Err.. Just to be clear, I never meant to suggesty ou'd take the ratio between month 1 and month 2. I tried to use parens to indicate the parameter that would be compared between the two groups (delayed and not delayed). Anything else wouldn't be an RCT, but just gawking at time series data...

by yyyk 6y ago

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%).
  - yyyk 6y ago
    >It suggested the neutralization titers were higher, not that they were ineffective. See figure B here taken from the study. That's a large difference to my completely untrained eye. https://twitter.com/AArgoetti/status/1359994177409478656 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.
    - mlyle 6y ago
      > See figure B here taken from the study. That's a large difference to my completely untrained eye. 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
      - yyyk 6y ago
        C'ya around. You'll make a fine educator - sure taught me a few things this time.

mlyle 6y ago

Err.. Just to be clear, I never meant to suggesty ou'd take the ratio between month 1 and month 2. I tried to use parens to indicate the parameter that would be compared between the two groups (delayed and not delayed). Anything else wouldn't be an RCT, but just gawking at time series data...