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A huge oversight was when it was approved for phrase III they should have run many (a dozen?) different trials at different dose amounts. It was already proven

A huge oversight was when it was approved for phrase III they should have run many (a dozen?) different trials at different dose amounts. It was already proven to be safe and nailing the dosing would have helped get shots into arms faster in the US and elsewhere. I'm on the extreme end of thinking it should have been approved faster - but even if you are a bit of a traditionalist I don't see how running concurrent trials on such an important potential vaccine wouldn't be a huge win.

tgsovlerkhgsel 5y ago
Or at least started running a second run of modified trials as soon as the phase 3 trials passed. The trials take something like 3 months from first shot to results, I think. It took a lot more than 3 months from phase 3 completed to most people vaccinated in most Western countries and obviously much longer in developing ones. But there is very little financial incentive to run such trials once you have a vaccine approved...
- handmodel 5y ago
  100% The problem is on the government side. They should have paid for this. It would have saved them money too - if it turned out they only needed to give out one shot of the mRNA doses or that they could cut down on dosage.
ebiester 5y ago
Tens of thousands were in this trial. How many hundreds of thousands of people should be sufficient to get it out the door?
- handmodel 5y ago
  It would still only be the same number of people per trial. They wouldn't have gotten trouble finding volunteers. And even if they just prioritized starting the first one ASAP - they didn't do any dosage testing until after it had been released to general public for months. Even if not ideal they could have started dosage trials in November after all the data from the original was done. Instead, they waited six months before even considering this.
  - belltaco 5y ago
    Even if you find all those multiple number of volunteers, you still need additional vaccine doses to be manufactured, which can take longer because they need more supplies from third parties, and scale up early. Not to mention all the extra staff to run the trials. If somehow they're able to run trials on 12x the volunteers, I would rather that they increase the participants by 12x for the final dose so that you get more confidence in the Phase 3 study results and in finding rare side effects.
- Spooky23 5y ago
  You have to be cautious as we live in an era where anti vaccine beliefs are commonplace.
loceng 5y ago
I'm curious what your knowledge or thoughts on potential non-vaccine treatments are like Ivernectin - and what you think of the response to them? Edit: ridiculous that HN community downvotes attempts to have conversation; you're part of the problem.
Spooky23 5y ago
Once manufacturing ramped I don’t think vaccine quantities are an issue. Transport, preparation and process are very operationally challenging.
belltaco 5y ago
It would be hard to recruit that many volunteers and staff to run a dozen trials, and reducing the study group size would mean less confidence in the results. Already we have seen blood clots and heart inflammation show up at rates that won't be caught even in larger scale trials.
mahogany 5y ago
Finding the optimal dose is done in phase II, where various dose levels are tested on different groups of people. Phase III happens after the dose level is confirmed, and then you roll that out to tens of thousands of people. I think the main point of phase III is to test the final candidate, so you're not really experimenting with the formula at that point. If you check the papers for the mRNA vaccines, you can see that they did run several different dose levels and got pretty clear feedback that some were too high or too low, before moving on to phase III.
- handmodel 5y ago
  I don't think this is accurate. If you read the abstract in phase II they gave it to a small amount of people and looked in detail how the immune system responded in these individuals. This is very granular data. Phase III is more like "We have no idea what the immune system did in certain people - but only 0.1% of vaccinated people ended up in hospital compared to 2% of placebo" or whatever. The important thing for the vaccine was too limit death and hospitalization. And phase II didn't tell us clear info on that. What if they had found that half the dosage ended up in the same number of hospitalizations? There's no way to get that from phase II data. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871769/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871769/
  - mahogany 5y ago
    Are you saying that my use of "clear feedback" isn't accurate? I mean this with respect to what was in scope for phase II, although I could see an argument against using that subjective language. Also, even more dosages were tested in phase I, again on a few number of people, but I'm not sure if that's different from how it's usually done. > The important thing for the vaccine was too limit death and hospitalization. And phase II didn't tell us clear info on that. Phase II is primarily to test that the "candidate is safe, sufficiently immunogenic, and maybe protective"[1]. It's not clear to me that testing hospitalization percentage is in scope. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/
    - 5y ago

tgsovlerkhgsel 5y ago

Or at least started running a second run of modified trials as soon as the phase 3 trials passed. The trials take something like 3 months from first shot to results, I think. It took a lot more than 3 months from phase 3 completed to most people vaccinated in most Western countries and obviously much longer in developing ones. But there is very little financial incentive to run such trials once you have a vaccine approved...

handmodel 5y ago
100% The problem is on the government side. They should have paid for this. It would have saved them money too - if it turned out they only needed to give out one shot of the mRNA doses or that they could cut down on dosage.

ebiester 5y ago

Tens of thousands were in this trial. How many hundreds of thousands of people should be sufficient to get it out the door?

handmodel 5y ago
It would still only be the same number of people per trial. They wouldn't have gotten trouble finding volunteers. And even if they just prioritized starting the first one ASAP - they didn't do any dosage testing until after it had been released to general public for months. Even if not ideal they could have started dosage trials in November after all the data from the original was done. Instead, they waited six months before even considering this.
- belltaco 5y ago
  Even if you find all those multiple number of volunteers, you still need additional vaccine doses to be manufactured, which can take longer because they need more supplies from third parties, and scale up early. Not to mention all the extra staff to run the trials. If somehow they're able to run trials on 12x the volunteers, I would rather that they increase the participants by 12x for the final dose so that you get more confidence in the Phase 3 study results and in finding rare side effects.
Spooky23 5y ago
You have to be cautious as we live in an era where anti vaccine beliefs are commonplace.

loceng 5y ago

I'm curious what your knowledge or thoughts on potential non-vaccine treatments are like Ivernectin - and what you think of the response to them? Edit: ridiculous that HN community downvotes attempts to have conversation; you're part of the problem.

Spooky23 5y ago

Once manufacturing ramped I don’t think vaccine quantities are an issue. Transport, preparation and process are very operationally challenging.

belltaco 5y ago

It would be hard to recruit that many volunteers and staff to run a dozen trials, and reducing the study group size would mean less confidence in the results. Already we have seen blood clots and heart inflammation show up at rates that won't be caught even in larger scale trials.

mahogany 5y ago

Finding the optimal dose is done in phase II, where various dose levels are tested on different groups of people. Phase III happens after the dose level is confirmed, and then you roll that out to tens of thousands of people. I think the main point of phase III is to test the final candidate, so you're not really experimenting with the formula at that point. If you check the papers for the mRNA vaccines, you can see that they did run several different dose levels and got pretty clear feedback that some were too high or too low, before moving on to phase III.

handmodel 5y ago
I don't think this is accurate. If you read the abstract in phase II they gave it to a small amount of people and looked in detail how the immune system responded in these individuals. This is very granular data. Phase III is more like "We have no idea what the immune system did in certain people - but only 0.1% of vaccinated people ended up in hospital compared to 2% of placebo" or whatever. The important thing for the vaccine was too limit death and hospitalization. And phase II didn't tell us clear info on that. What if they had found that half the dosage ended up in the same number of hospitalizations? There's no way to get that from phase II data. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871769/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871769/
- mahogany 5y ago
  Are you saying that my use of "clear feedback" isn't accurate? I mean this with respect to what was in scope for phase II, although I could see an argument against using that subjective language. Also, even more dosages were tested in phase I, again on a few number of people, but I'm not sure if that's different from how it's usually done. > The important thing for the vaccine was too limit death and hospitalization. And phase II didn't tell us clear info on that. Phase II is primarily to test that the "candidate is safe, sufficiently immunogenic, and maybe protective"[1]. It's not clear to me that testing hospitalization percentage is in scope. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944327/
  - 5y ago