3 ms·

Yes, but there are also plenty of ways bias can creep into an RCT. Also remember we're not talking about the same virus - the trials were on 'vanilla' virus whi

by yyyk 6y ago

Yes, but there are also plenty of ways bias can creep into an RCT. Also remember we're not talking about the same virus - the trials were on 'vanilla' virus while by the time Pfizer arrived to Israel en mass B117 was prevalent. It could be the 1st dose is less efficient with B117. That's close to what the other link I provided earlier[0] argued. Can decision makers really take that risk? [0] https://www.researchsquare.com/article/rs-226857/v1 https://www.researchsquare.com/article/rs-226857/v1 Earlier I linked to a short twitter thread explaining the article.

mlyle 6y ago
> but there are also plenty of ways bias can creep into an RCT. Yes, but in this case generally in the direction towards less efficacy too. People are unblinded inadvertently by their side effects and then act more recklessly, etc. And this is immaterial: yes, RCTs can be fucked up, but CCTs are almost always fucked up. > Also remember we're not talking about the same virus - the trials were on 'vanilla' virus while by the time Pfizer arrived to Israel en mass B117 was prevalent. It could be the 1st dose is less efficient with B117. That's close to what the other link I provided earlier[0] argued. It could be. Anything could be. The question is the likelihood. But the other source arguing negative efficacy when even shitty case control data is showing positive efficacy is a little dubious. Indeed, the hwole core assumption on that time series data is so bad-- assuming that people will behave the same from days 0-7 and from 7 on, when they've been cautioned that the vaccine is not immediately effective... Seriously, smh. > Can decision makers really take that risk? To do what I suggested? Yes. I suggested to run a trial. Don't pretend that I suggested anything different to strengthen your case. It's a trial exceptionally likely to yield positive results for delaying the second dose.
- yyyk 6y ago
  [EDIT: Removed an irrelevant paragraph.] There were suggestions earlier that 1st dose was "for sure" more effective, and judging by UK response some countries are desperate enough to try this without a trial. You didn't mean it, but it's possible some places will go for it. I'm just asking people to look before they leap, it's not a sure thing. >Indeed, the whole core assumption on that time series data is so bad-- assuming that people will behave the same from days 0-7 and from 7 on, when they've been cautioned that the vaccine is not immediately effective... Seriously, smh. Well, according to his github explanation[0] there was an attempt to account for that: "It is assumed that on the days following the vaccination, there is increased caution to avoid social encounters." [0] https://github.com/dviraran/covid_analyses https://github.com/dviraran/covid_analyses
  - mlyle 6y ago
    Well, you're trying my patience by putting words in my mouth that I didn't say: I didn't suggest decisionmakers immediately give everyone one dose. Are you making a dishonest argument, or did you just fail to read what I originally said. Your assertions are hard to reconcile with e.g. https://pbs.twimg.com/media/Et4moRCXAAAZ18o?format=jpg&name=large 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...
    - yyyk 6y ago
      I didn't mean to put anything in your mouth you did not say. If I accidentally offended you please accept my apology. Lets keep this to the science, as far as my limited ability allows me to engage, OK? 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_1002_post.pdf https://kinstitute.org.il/wp-content/uploads/2021/02/covid_1... [1] https://twitter.com/KalksteinNir/status/1358735186637299715 https://twitter.com/KalksteinNir/status/1358735186637299715
      - mlyle 6y ago
        It's time series data. Yes, it's not case controlled. I said this already. 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).

by yyyk 6y ago

mlyle 6y ago

> but there are also plenty of ways bias can creep into an RCT. Yes, but in this case generally in the direction towards less efficacy too. People are unblinded inadvertently by their side effects and then act more recklessly, etc. And this is immaterial: yes, RCTs can be fucked up, but CCTs are almost always fucked up. > Also remember we're not talking about the same virus - the trials were on 'vanilla' virus while by the time Pfizer arrived to Israel en mass B117 was prevalent. It could be the 1st dose is less efficient with B117. That's close to what the other link I provided earlier[0] argued. It could be. Anything could be. The question is the likelihood. But the other source arguing negative efficacy when even shitty case control data is showing positive efficacy is a little dubious. Indeed, the hwole core assumption on that time series data is so bad-- assuming that people will behave the same from days 0-7 and from 7 on, when they've been cautioned that the vaccine is not immediately effective... Seriously, smh. > Can decision makers really take that risk? To do what I suggested? Yes. I suggested to run a trial. Don't pretend that I suggested anything different to strengthen your case. It's a trial exceptionally likely to yield positive results for delaying the second dose.

yyyk 6y ago
[EDIT: Removed an irrelevant paragraph.] There were suggestions earlier that 1st dose was "for sure" more effective, and judging by UK response some countries are desperate enough to try this without a trial. You didn't mean it, but it's possible some places will go for it. I'm just asking people to look before they leap, it's not a sure thing. >Indeed, the whole core assumption on that time series data is so bad-- assuming that people will behave the same from days 0-7 and from 7 on, when they've been cautioned that the vaccine is not immediately effective... Seriously, smh. Well, according to his github explanation[0] there was an attempt to account for that: "It is assumed that on the days following the vaccination, there is increased caution to avoid social encounters." [0] https://github.com/dviraran/covid_analyses https://github.com/dviraran/covid_analyses
- mlyle 6y ago
  Well, you're trying my patience by putting words in my mouth that I didn't say: I didn't suggest decisionmakers immediately give everyone one dose. Are you making a dishonest argument, or did you just fail to read what I originally said. Your assertions are hard to reconcile with e.g. https://pbs.twimg.com/media/Et4moRCXAAAZ18o?format=jpg&name=large 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...
  - yyyk 6y ago
    I didn't mean to put anything in your mouth you did not say. If I accidentally offended you please accept my apology. Lets keep this to the science, as far as my limited ability allows me to engage, OK? 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_1002_post.pdf https://kinstitute.org.il/wp-content/uploads/2021/02/covid_1... [1] https://twitter.com/KalksteinNir/status/1358735186637299715 https://twitter.com/KalksteinNir/status/1358735186637299715
    - mlyle 6y ago
      It's time series data. Yes, it's not case controlled. I said this already. 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).