4 ms·

I don't get why nobody seriously considers a one-dose regimen for the fastest possible vaccine rollout. All available data for both, Biontech/Pfizer and Moderna

by jpdus 6y ago

I don't get why nobody seriously considers a one-dose regimen for the fastest possible vaccine rollout. All available data for both, Biontech/Pfizer and Moderna's vaccines suggests that one dose is enough for >90% efficacy which would be sufficient to reach herd immunity. There was a very good opinion article in the NY Times [1] about that, but not much more. The problem here is that a one-dose regimen was not studied in the trials. While it is good medical practice do not deviate from trial designs (see the Oxford/AZ vaccine), the data is very clear here. The vaccines are effective 14 days after the first dose and before the second dose. Sure, there are risks (maybe the efficacy drops later on or it is more difficult to reach the full efficacy if the booster shot is delayed) but these risks seem to be negligible compared to the hundreds of thousands additional unnecessary deaths due to limited vaccine supply and delayed vaccination with a two-shot regimen. We know from other vaccines that the timing of the booster shot normally is not that important and it is very probably that a booster shot after a few months would be exactly as good as a booster shot after 4 weeks. In my opinion, nobody seriously contemplates the one-dose regimen because somebody has to take responsibility to deviate from the proven and tested protocol - politicians have nothing to win here but much to loose in case anything goes wrong. And big pharma has no interest in financing and starting one-dose trials asap b/c it would hurt their own bottom line and there is no financial incentive at all, quite the opposite (+they have the same responsibility problem). This is a deadlock which will cost many, many lifes. [1] https://www.nytimes.com/2020/12/18/opinion/coronavirus-vaccine-doses.html https://www.nytimes.com/2020/12/18/opinion/coronavirus-vacci...

tehjoker 6y ago
That's not what the Pfizer paper showed. There was a confidence interval from between 20-70% iirc for the first shot. Maybe if we're lucky it's on the higher end, but I would stick to proven science if we're going to combat this thing effectively.
- deleted 6y ago
  [deleted]
- mlyle 6y ago
  Wargame the scenarios. You wouldn't want to give one dose on purpose, but reserving a whole bunch of doses to prevent some people from getting only 1 in a worst case scenario is silly. That 20-70% efficacy number includes the entire period between dose 1 and 2. It looks way better 10 days after dose 1, btw-- MLE around 80%. e.g. single dose -- 50% efficacy (to be pessimistic); double dose -- 95% efficacy. 10M doses "in flight" monthly. 100 deaths/million/month. Ignore all effects on transmission (to be more pessimistic). Scenario 1 (no logistics disruption, half held back): 5M dosed with 1 dose at day 0, 5M dosed with 2 doses at 1 month and 5M dosed with 1 dose at 1 month. 250 saved in first month, 725 saved in second month. Scenario 2 (no logistics disruption, 25% held back): 7.5M dosed with 1 dose at day 0, 7.5M dosed with 2 doses at 1 month and 2.5M dosed with 1 dose at 1 month. 375 saved in first month, 837 saved in second month. Scenario 3: (100% production disruption, half held back): 5M dosed with 1 dose at day 0; 5M dosed with 2 doses at 1 month. 250 saved in first month, 475 saved in second month. Scenario 4: (100% production disruption, 25% held back): 7.5M dosed with 1 dose at day 0; 2.5M dosed with 2 doses at 1 month; (5M late for dose 2); 375 saved in first month, 612 saved in second month. With a 25% reserve, you only get into the unexpected-only-1-dose regimen with a supply disruption of more than 50%... and even then it's still probably better than a 50% reserve.
  - wwweston 6y ago
    This is a productive line of thinking.
  - tehjoker 6y ago
    I wonder if hitting the delivery targets of 20M per month is going to be achieved. That's the first bottleneck before the vaccine supply.
    - mlyle 6y ago
      Right now, many jurisdictions are supply limited, and most look like they're ramping enough to be supply limited, though still a bit more slowly than I'd like. Lowering reserves would still increase administration rate immediately (though not proportionally). Actually, we might even enter phase 1B in some areas and have a mostly parallel administration system start to come up... It's unclear to me how much of the slowness so far in administration (13.5% of doses allotted are reported as administered so far)... is A) (fixed?) delays in reporting, B) (fixed?) delays in logistics getting doses to administration sites, C) limitations on rate of administration, D) holiday-related slowness. Only C really matters in the long term-- if it is ramping poorly compared to production than that's a problem. But I think it's premature to assume C is limiting when A, B, & D are surely large right now.
- aquadrop 6y ago
  Did you see that graph with amount of cases in control/vaccine groups? Where around day 10 vaccine group graph shows massive drop. It looks pretty convincing. And by now they have much more data, especially with lots of cases nowadays. That simple move can save thousands of live and I think worth considering, instead of just ignoring everything.
  - tehjoker 6y ago
    I just reviewed it and somehow I missed that detail that the inflection point was way before the second vaccine on the first reading. Very interesting.
- tehjoker 6y ago
  Note reviewing the paper: 95% CI 29.5% to 68.4%, mean vaccine efficacy prediction 52% for 1st shot.
- jpdus 6y ago
  That is not correct (I think that number comes from the Oxford/AZ vaccine?). If you look at the cumulative incidence curves (for Moderna see [1] page 28), you can see that COVID-19 occurences drop approx. 14 days after the first dose with no measurable effect of the second dose after 28 days. This pattern is exactly the same for both vaccines. [1] https://www.fda.gov/media/144434/download https://www.fda.gov/media/144434/download PS: My parent comment was downvoted more often than any other HN comment I ever made, but nobody cared to elaborate why my line of thinking is unethical or why i am reading the data wrong. That's slightly disappointing.
aquadrop 6y ago
Exactly, I'm baffled by this as well. It's a simple and clear way to save many more lives and nobody even discussing this. It's also much easier to administer since you don't need to coordinate second visit. I don't understand why it wasn't part of the trial (some portion of people just get 1 dose)

by jpdus 6y ago

tehjoker 6y ago

That's not what the Pfizer paper showed. There was a confidence interval from between 20-70% iirc for the first shot. Maybe if we're lucky it's on the higher end, but I would stick to proven science if we're going to combat this thing effectively.

deleted 6y ago
[deleted]
mlyle 6y ago
Wargame the scenarios. You wouldn't want to give one dose on purpose, but reserving a whole bunch of doses to prevent some people from getting only 1 in a worst case scenario is silly. That 20-70% efficacy number includes the entire period between dose 1 and 2. It looks way better 10 days after dose 1, btw-- MLE around 80%. e.g. single dose -- 50% efficacy (to be pessimistic); double dose -- 95% efficacy. 10M doses "in flight" monthly. 100 deaths/million/month. Ignore all effects on transmission (to be more pessimistic). Scenario 1 (no logistics disruption, half held back): 5M dosed with 1 dose at day 0, 5M dosed with 2 doses at 1 month and 5M dosed with 1 dose at 1 month. 250 saved in first month, 725 saved in second month. Scenario 2 (no logistics disruption, 25% held back): 7.5M dosed with 1 dose at day 0, 7.5M dosed with 2 doses at 1 month and 2.5M dosed with 1 dose at 1 month. 375 saved in first month, 837 saved in second month. Scenario 3: (100% production disruption, half held back): 5M dosed with 1 dose at day 0; 5M dosed with 2 doses at 1 month. 250 saved in first month, 475 saved in second month. Scenario 4: (100% production disruption, 25% held back): 7.5M dosed with 1 dose at day 0; 2.5M dosed with 2 doses at 1 month; (5M late for dose 2); 375 saved in first month, 612 saved in second month. With a 25% reserve, you only get into the unexpected-only-1-dose regimen with a supply disruption of more than 50%... and even then it's still probably better than a 50% reserve.
- wwweston 6y ago
  This is a productive line of thinking.
- tehjoker 6y ago
  I wonder if hitting the delivery targets of 20M per month is going to be achieved. That's the first bottleneck before the vaccine supply.
  - mlyle 6y ago
    Right now, many jurisdictions are supply limited, and most look like they're ramping enough to be supply limited, though still a bit more slowly than I'd like. Lowering reserves would still increase administration rate immediately (though not proportionally). Actually, we might even enter phase 1B in some areas and have a mostly parallel administration system start to come up... It's unclear to me how much of the slowness so far in administration (13.5% of doses allotted are reported as administered so far)... is A) (fixed?) delays in reporting, B) (fixed?) delays in logistics getting doses to administration sites, C) limitations on rate of administration, D) holiday-related slowness. Only C really matters in the long term-- if it is ramping poorly compared to production than that's a problem. But I think it's premature to assume C is limiting when A, B, & D are surely large right now.
aquadrop 6y ago
Did you see that graph with amount of cases in control/vaccine groups? Where around day 10 vaccine group graph shows massive drop. It looks pretty convincing. And by now they have much more data, especially with lots of cases nowadays. That simple move can save thousands of live and I think worth considering, instead of just ignoring everything.
- tehjoker 6y ago
  I just reviewed it and somehow I missed that detail that the inflection point was way before the second vaccine on the first reading. Very interesting.
tehjoker 6y ago
Note reviewing the paper: 95% CI 29.5% to 68.4%, mean vaccine efficacy prediction 52% for 1st shot.
jpdus 6y ago
That is not correct (I think that number comes from the Oxford/AZ vaccine?). If you look at the cumulative incidence curves (for Moderna see [1] page 28), you can see that COVID-19 occurences drop approx. 14 days after the first dose with no measurable effect of the second dose after 28 days. This pattern is exactly the same for both vaccines. [1] https://www.fda.gov/media/144434/download https://www.fda.gov/media/144434/download PS: My parent comment was downvoted more often than any other HN comment I ever made, but nobody cared to elaborate why my line of thinking is unethical or why i am reading the data wrong. That's slightly disappointing.

aquadrop 6y ago

Exactly, I'm baffled by this as well. It's a simple and clear way to save many more lives and nobody even discussing this. It's also much easier to administer since you don't need to coordinate second visit. I don't understand why it wasn't part of the trial (some portion of people just get 1 dose)