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It is unfortunate. You can't even avoid downvotes in a fairly rational place like HN :) . I've been following the vaccine development pretty closely and everyt

It is unfortunate. You can't even avoid downvotes in a fairly rational place like HN :) . I've been following the vaccine development pretty closely and everything looks like a "this can't fail" mentality. People need to realize that it's rational to ask if we really need the dose this high and really need a booster because if we find out we don't, it could double or even quadruple our vaccine supply. That could save half a million lives. It's good to ask questions like this especially when there's a massive worldwide vaccine shortage

Guthur 6y ago
Given HN propensity to bash corporations I'm surprised this is not seen as a way to double or triple profits :)
- throwaway189262 6y ago
  Indeed. But to bash the large corpos, when medical staff figured out they could get an extra dose from most vials the drug companies immediately reduced their shipment contract requirements accordingly. Pretty scummy.
Espressosaurus 6y ago
This is a case of "let's go with what works, because the downsides are worse", and we can simultaneously kick off studies of other approaches. When those are proven out (or not) changes in the protocols can be applied then. Blindly changing the protocols without proper controls/studies done in widescale deployment and hoping for the best is a great way to screw things up.
- mlyle 6y ago
  A good way to do this: enroll people who have had dose 1 but not dose 2. Give half of them dose 2 and half placebo at the normal interval; then at double interval give those that hadn't gotten dose 2 yet their second dose. This can cut a month off the trial. I also think you don't need a full 4 months of data for this-- just enough to show not-gross-inferiority.
  - tw04 6y ago
    Who would volunteer for that study? It would be horribly unethical to give people a placebo who didn't volunteer.
    - mlyle 6y ago
      I'd volunteer. I'm 41 and about to be up for my turn as an educator. I feel OK about the mitigations in my classroom and my overall level of risk, and a bit guilty about getting my dose earlier than most; a 50-50 chance of delaying my second dose doesn't appreciably make the risk picture worse. If my second dose was delayed, odds are I'd end up with better long term immunity, too, even though my risk in the intermediate period would be higher. > It would be horribly unethical to give people a placebo who didn't volunteer. No shit. That's why I said "enroll" -- this includes getting consent. I suspect finding 20k people to volunteer out of the ~10M dosed per week wouldn't be that hard.
    - renewiltord 6y ago
      I’d volunteer for a challenge trial, so obviously I’d volunteer for this.
    - skybrian 6y ago
      Why not volunteer? One dose is apparently quite protective already. Most likely, there will be little difference which arm of the trial you end up on.
    - astura 6y ago
      I would.
    - Rebelgecko 6y ago
      It could be beneficial for people that are further down the priority list and want to get vaccinated sooner. Especially since the people further down the list are less likely to die if they do get covid
    - xboxnolifes 6y ago
      The same kind of people who already enroll in any other kind of drug trial. "Who would volunteer for that study" doesn't make much sense of a question considering people are willing to do phase 0 studies of new drugs which are theoretically far more dangerous.
- BurningFrog 6y ago
  But it's not "blindly". We know a lot about how vaccines and the human immune system works without going through the ritual of a full scale trial for every parameter tweak. That knowledge strongly indicates that half doses will work just as well as the dose that happened to be chosen for the first trial. Waiting several months for these studies have the major downsides that thousands of people die each day we wait. To make a rational decision, that potential benefit needs to be weighed against the potential risk, but that is usually left out of these arguments.
mxcrossb 6y ago
Why is the development “this can’t fail” but the distribution isn’t? If we cut corners on distribution (and compound that with the real world flaws in the process) and you screw up, it would be a huge disaster. You would complete undermine the public’s faith in vaccines and lockdowns.
- mattmanser 6y ago
  It's a gamble the British government are already taking, they decided to extend the time between doses to give me people the first dose sooner. We'll start to see in 8 weeks or so if it was worth it.
- barry-cotter 6y ago
  If the vaccine developers fail their companies lose lots of money and their bosses are mad at them. There’s a tiny possibility they might lose their jobs and it certainly won’t look good for promotion purposes. Also, developing vaccines is something they actually know how to do. If civil servants fuck up in ways that delay or prevent progress in fighting COVID there are no consequences. No one gets fired or reprimanded, whether for what they said about masks, preventing home testing, telling the Seattle Flu Study they couldn’t test for COVID in February, fining distillers for making hand sanitizer... And note the US FDA and CDC are at worst only a little worse than the European Medical Authority. Slower at approving more or less everything, like KN95s or the J&J vaccine, but they’re not actively trying to kill people. They’re just making sure they can’t be blamed for approving something unsafe. The people who die as a result of that delay are not their problem.
  - Spooky23 6y ago
    That’s nonsense government griping. In fact, we had an election and fired all of those decision makers. Rushing through things like KN-95 has consequences. My brother is a firefighter paramedic and found out that 90% of the kn95 masks issued to him were completely defective.
    - wwweston 6y ago
jonstewart 6y ago
O Rational, rational, wherefore art thou rational? Deny thy prior and refuse thy game Or if trials not, warranty void of And I’ll no longer make a captious bet.
WalterBright 6y ago
I'd be first in line to get a vaccine even if it was less than 10% effective.
4eor0 6y ago
“Hindsight is 20/20.” Of all the failures in the system that could have prevented lives, this seems like the least egregious. What people need to realize is politically inclined or no, restricting political involvement to an election every 2-4 years, letting it optimize for fiscal efficiency, not resiliency and reliability, has killed a whole lot more people than extra caution over dosage. None of the general public control drug companies. They could control the government. I’m all in on being a big corp sycophant because the general public are clearly incompetent political agents by enabling a bigger mess than necessary in the first place.
dkural 6y ago
Maybe because HN is rational, and thus doesn't like the factual inaccuracies in your post? 1) There were no adjuvants used 2) Antibody response doesn't linearly correlate with protection. Many vaccines provoke a higher antibody response but much less efficacy compared to the Moderna and Pfizer/BioNTech vaccine. 3) mRNA is an entirely new modality, it's not like people knew before-hand what would work, given point 2. I don't think anyone is arguing that IF the booster is not needed, then we shouldn't double the vaccine supply. Consider the following risk however: There is such a thing called vaccine resistance. A weakly immunized patient becomes a training ground for novel variants of the virus that then starts spreading & vaccine doesn't work.
- Closi 6y ago
  I don’t think OP claimed any of this, at least in my reading. All of these things are trade offs anyway - a weaker immunised patient might become a training ground for a variant, but a weakly immunised patient might also have a reduced risk of spreading which results in fewer cases and fewer chances for mutations.
stjohnswarts 6y ago
We can save those experiments for when there isn't 450,000 Americans dead from covid. I prefer the go early go hard approach. There will be a second round of Covid-21, the South African mutated version is proving that.
_ph_ 6y ago
Well, this really can't fail. The challenge was to develop a ready-to market vaccine in the shortest possible time and several companies managed this task. That is why millions are already vaccinated. Yes, you are allowed to ask questions, but why do you assume that all the involved experts at the pharmaceutical companies didn't ask those questions? And as far as I am aware, they did investigate different dosages. So what we got now is their best effort given the many competing requirements. And yes, they might have a bit generous, but only a bit, as higher doses do create stronger side effects. And I am very happy they did, considering the mutations appeared in the meantime and the vaccines are still effective. I am sure, the vaccines are going to be further optimized as more time goes by and especially more data becomes available.
- hitpointdrew 6y ago
  > but why do you assume that all the involved experts at the pharmaceutical companies didn't ask those questions? Because they have a financial incentive not to ask those.
- BurningFrog 6y ago
  > why do you assume that all the involved experts at the pharmaceutical companies didn't ask those questions? Pharmaceutical company employees have no power over FDA decisions. > And as far as I am aware, they did investigate different dosages. They did, and the result was that half doses produce as strong an immune response as full doses. This is the basis for this "let's do half doses" argument! The study was done with the bigger dose, and showed 95% protection. So we know that (1) dose A has the same effect as dose B, and (2) dose B provides 95% protection. Obviously (1)+(2) logically implies that using dose A would give twice as many people the same immunity. But logic is not part of the FDA regulatory framework. You have to blindly repeat the protocol of the study, whether it makes sense or not. Whether thousands die or not.

Guthur 6y ago

Given HN propensity to bash corporations I'm surprised this is not seen as a way to double or triple profits :)

throwaway189262 6y ago
Indeed. But to bash the large corpos, when medical staff figured out they could get an extra dose from most vials the drug companies immediately reduced their shipment contract requirements accordingly. Pretty scummy.

Espressosaurus 6y ago

This is a case of "let's go with what works, because the downsides are worse", and we can simultaneously kick off studies of other approaches. When those are proven out (or not) changes in the protocols can be applied then. Blindly changing the protocols without proper controls/studies done in widescale deployment and hoping for the best is a great way to screw things up.

mlyle 6y ago
A good way to do this: enroll people who have had dose 1 but not dose 2. Give half of them dose 2 and half placebo at the normal interval; then at double interval give those that hadn't gotten dose 2 yet their second dose. This can cut a month off the trial. I also think you don't need a full 4 months of data for this-- just enough to show not-gross-inferiority.
- tw04 6y ago
  Who would volunteer for that study? It would be horribly unethical to give people a placebo who didn't volunteer.
  - mlyle 6y ago
    I'd volunteer. I'm 41 and about to be up for my turn as an educator. I feel OK about the mitigations in my classroom and my overall level of risk, and a bit guilty about getting my dose earlier than most; a 50-50 chance of delaying my second dose doesn't appreciably make the risk picture worse. If my second dose was delayed, odds are I'd end up with better long term immunity, too, even though my risk in the intermediate period would be higher. > It would be horribly unethical to give people a placebo who didn't volunteer. No shit. That's why I said "enroll" -- this includes getting consent. I suspect finding 20k people to volunteer out of the ~10M dosed per week wouldn't be that hard.
  - renewiltord 6y ago
    I’d volunteer for a challenge trial, so obviously I’d volunteer for this.
  - skybrian 6y ago
    Why not volunteer? One dose is apparently quite protective already. Most likely, there will be little difference which arm of the trial you end up on.
  - astura 6y ago
    I would.
  - Rebelgecko 6y ago
    It could be beneficial for people that are further down the priority list and want to get vaccinated sooner. Especially since the people further down the list are less likely to die if they do get covid
  - xboxnolifes 6y ago
    The same kind of people who already enroll in any other kind of drug trial. "Who would volunteer for that study" doesn't make much sense of a question considering people are willing to do phase 0 studies of new drugs which are theoretically far more dangerous.
BurningFrog 6y ago
But it's not "blindly". We know a lot about how vaccines and the human immune system works without going through the ritual of a full scale trial for every parameter tweak. That knowledge strongly indicates that half doses will work just as well as the dose that happened to be chosen for the first trial. Waiting several months for these studies have the major downsides that thousands of people die each day we wait. To make a rational decision, that potential benefit needs to be weighed against the potential risk, but that is usually left out of these arguments.

mxcrossb 6y ago

Why is the development “this can’t fail” but the distribution isn’t? If we cut corners on distribution (and compound that with the real world flaws in the process) and you screw up, it would be a huge disaster. You would complete undermine the public’s faith in vaccines and lockdowns.

mattmanser 6y ago
It's a gamble the British government are already taking, they decided to extend the time between doses to give me people the first dose sooner. We'll start to see in 8 weeks or so if it was worth it.
barry-cotter 6y ago
If the vaccine developers fail their companies lose lots of money and their bosses are mad at them. There’s a tiny possibility they might lose their jobs and it certainly won’t look good for promotion purposes. Also, developing vaccines is something they actually know how to do. If civil servants fuck up in ways that delay or prevent progress in fighting COVID there are no consequences. No one gets fired or reprimanded, whether for what they said about masks, preventing home testing, telling the Seattle Flu Study they couldn’t test for COVID in February, fining distillers for making hand sanitizer... And note the US FDA and CDC are at worst only a little worse than the European Medical Authority. Slower at approving more or less everything, like KN95s or the J&J vaccine, but they’re not actively trying to kill people. They’re just making sure they can’t be blamed for approving something unsafe. The people who die as a result of that delay are not their problem.
- Spooky23 6y ago
  That’s nonsense government griping. In fact, we had an election and fired all of those decision makers. Rushing through things like KN-95 has consequences. My brother is a firefighter paramedic and found out that 90% of the kn95 masks issued to him were completely defective.
  - wwweston 6y ago

jonstewart 6y ago

O Rational, rational, wherefore art thou rational? Deny thy prior and refuse thy game Or if trials not, warranty void of And I’ll no longer make a captious bet.

WalterBright 6y ago

I'd be first in line to get a vaccine even if it was less than 10% effective.

4eor0 6y ago

“Hindsight is 20/20.” Of all the failures in the system that could have prevented lives, this seems like the least egregious. What people need to realize is politically inclined or no, restricting political involvement to an election every 2-4 years, letting it optimize for fiscal efficiency, not resiliency and reliability, has killed a whole lot more people than extra caution over dosage. None of the general public control drug companies. They could control the government. I’m all in on being a big corp sycophant because the general public are clearly incompetent political agents by enabling a bigger mess than necessary in the first place.

dkural 6y ago

Maybe because HN is rational, and thus doesn't like the factual inaccuracies in your post? 1) There were no adjuvants used 2) Antibody response doesn't linearly correlate with protection. Many vaccines provoke a higher antibody response but much less efficacy compared to the Moderna and Pfizer/BioNTech vaccine. 3) mRNA is an entirely new modality, it's not like people knew before-hand what would work, given point 2. I don't think anyone is arguing that IF the booster is not needed, then we shouldn't double the vaccine supply. Consider the following risk however: There is such a thing called vaccine resistance. A weakly immunized patient becomes a training ground for novel variants of the virus that then starts spreading & vaccine doesn't work.

Closi 6y ago
I don’t think OP claimed any of this, at least in my reading. All of these things are trade offs anyway - a weaker immunised patient might become a training ground for a variant, but a weakly immunised patient might also have a reduced risk of spreading which results in fewer cases and fewer chances for mutations.

stjohnswarts 6y ago

We can save those experiments for when there isn't 450,000 Americans dead from covid. I prefer the go early go hard approach. There will be a second round of Covid-21, the South African mutated version is proving that.

_ph_ 6y ago

Well, this really can't fail. The challenge was to develop a ready-to market vaccine in the shortest possible time and several companies managed this task. That is why millions are already vaccinated. Yes, you are allowed to ask questions, but why do you assume that all the involved experts at the pharmaceutical companies didn't ask those questions? And as far as I am aware, they did investigate different dosages. So what we got now is their best effort given the many competing requirements. And yes, they might have a bit generous, but only a bit, as higher doses do create stronger side effects. And I am very happy they did, considering the mutations appeared in the meantime and the vaccines are still effective. I am sure, the vaccines are going to be further optimized as more time goes by and especially more data becomes available.

hitpointdrew 6y ago
> but why do you assume that all the involved experts at the pharmaceutical companies didn't ask those questions? Because they have a financial incentive not to ask those.
BurningFrog 6y ago
> why do you assume that all the involved experts at the pharmaceutical companies didn't ask those questions? Pharmaceutical company employees have no power over FDA decisions. > And as far as I am aware, they did investigate different dosages. They did, and the result was that half doses produce as strong an immune response as full doses. This is the basis for this "let's do half doses" argument! The study was done with the bigger dose, and showed 95% protection. So we know that (1) dose A has the same effect as dose B, and (2) dose B provides 95% protection. Obviously (1)+(2) logically implies that using dose A would give twice as many people the same immunity. But logic is not part of the FDA regulatory framework. You have to blindly repeat the protocol of the study, whether it makes sense or not. Whether thousands die or not.