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An issue that I basically never see come up is - why not administer the vaccine earlier on (pre-approval) to the most vulnerable? if P(death|vaccine) < P(death|

An issue that I basically never see come up is - why not administer the vaccine earlier on (pre-approval) to the most vulnerable? if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it. Many dead people now could be alive had that been done (and mRNA candidates were apparently available extremely early on). The Oxford vaccine is a more classical one so wasn't available quite as early, but apparently the mRNA ones were developed in a very short space of time (weeks - months) and future development could cut that even further (and preemptive vaccines for potential pandemic-causing viruses could be kept in stock) - perhaps introducing a Bayesian triage pre-approval could be an important strategy in fighting viruses in the future? In any case this and the mRNA vaccines are really tremendous achievements and somewhat restores my faith in humanity after a terrible year...

odnes 6y ago
> An issue that I basically never see come up is - why not administer the vaccine earlier on (pre-approval) to the most vulnerable? if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it. Not sure, but I would think it comes down to hospitals not being overrun in the case of a widescale negative response to the vaccine. But since the whole thing is a game of probabilities, I do share your view.
- barnacled 6y ago
  You could distribute it in limited batches to only the most vulnerable which should reduce any risk of that. I think the most vulnerable are in any case most likely to already be heavily using the health services anyway (and would be the ones engaging them the most if they caught the virus).
- hef19898 6y ago
  Because of ethics in drug development. And these rules are there for a reason. Not sure what could have been done better with Covid vaccines, we have three now roughly a year after the first cases. All of them work and are either certified or on the track to soon be. We even have four if you include the Russian one. Summing up the ethics part: Studies include volunteers in a controlled environment. Just administering un approved stuff to people means using people as guinea pigs. I don't want that, and it is doubtful we would have gained anything. Because now it is "simple" distribution and production problem.
  - barnacled 6y ago
    'Because of ethics' and 'these rules are there for a reason' are not arguments, they're 'shut up' encoded. Present arguments please. The progress of the vaccine has been incredible compared to usual, but that doesn't mean more could have been done. Every death is a tragedy. People are constantly used as guinea pigs... as long as there is informed consent as per the Nuremberg code it's fine. Not suggesting anybody would be forced or ill-informed. So back to my argument - you can make a reasonable guess at estimating P(death|vaccine) vs. P(death|covid) and set a big margin, then offer people to VOLUNTARILY agree to take it who are most at risk of dying. The average age of death in the UK is 82 mostly with co-morbidities. I am sure many of these dead would have been happy to take the chance. And in the case of the mRNA vaccines this not some trivial difference - some were developed within weeks/months, but took nearly a year longer to pass all testing. It's really obvious that pandemics need different handling than the 'lock down and loads of people die anyway, both from the virus and the consequences of lockdown while ruining the economy + wait 2yrs for a vaccine to be fully distributed' approach we've got. I hope lessons are learned from covid (I'm actually optimistic they will be, in countries other than the one where the virus emerged anyway).
    - hef19898 6y ago
      > I am sure ... many would have taken the chances So you never asked anyone. The problem is, if you ignore ethics, which of course says a lot about your priorities, still two fold. First, you have development. That was arguably the fastest vaccine development in history. Not sure what could have been done faster here. Second, you have production and distribution. Ramping up these two doesn't make much sense before you know whether or not the vaccines work. Now they are ramped up really fast. Going "fast and breaking" things may have resulted in more people being vaccinated early on. But this small benefit would have caused tremendous issues in a couple of weeks / months. The goal is to get millions vaccinated, not just a few elderly so that some people can go out partying again without feeling bad.
      - barnacled 6y ago
        >So you never asked anyone. The problem is, if you ignore ethics, which of course says a lot about your priorities, still two fold. This is offensive and I suggest you re-read my post (as well as the HN comment guidelines). I am not ignoring ethics, I specifically mention informed consent. I also have no idea what you mean by 'so you never asked anyone' - this is a hypothetical?? >The goal is to get millions vaccinated, not just a few elderly so that some people can go out partying again without feeling bad. You're also strawmanning me pretty hard here. > But this small benefit would have caused tremendous issues in a couple of weeks / months. Not even sure how you come to this conclusion (you seem 100% certain that distributing the now-proven safe mRNA vaccine early would have caused tremendous issues, somehow). You seem to want to be aggressive to me and strawman me as somebody who doesn't care about covid victims (my grandmother is 85 and has serious comorbidity risks thank you very much) so I am not going to respond further but I suggest you focus on arguments, not insults and dismissive comments. You can go to reddit and much of the rest of the internet for that.
BlackVanilla 6y ago
> why not administer the vaccine earlier on (pre-approval) to the most vulnerable? The issue is less tangible and less quantative that that. It's about trust and public buy-in. If vaccine is rolled out despite not fully understanding its efficacy and safety and there are even minor side-effects, there will be fewer people who take the vaccine when they are asked to do so.
- barnacled 6y ago
  At the cost of how many lives? And if the vaccine is successful how would that harm buy-in? If not then it's a failed experiment (though obviously the PR impact could be rather negative!) I think it's pretty clear from the past year that we need different tools and approaches to dealing with pandemics. One part is clearly faster vaccine development (mRNA seems very promising for this) and pre-emptive vaccine development, another might be permitting very much informed consent take up early on.
  - dazzawazza 6y ago
    The cost of a dangerous vaccine could be one hundred years of lower uptake of ALL vaccines decimating the populations of nearly every country in the world. Not worth the risk if you ask me.
    - barnacled 6y ago
      I'm not sure a small subset having a bad reaction to a known-untested vaccine they volunteered to have would have quite as bad an impact as you say, certainly not 100 years of lower uptake! It would likely have some kind of an impact though, and give fuel to anti-vaxxer types (yuk) but I am not sure the impact would be quite so severe.
randcraw 6y ago
[...] why not administer the vaccine earlier on (pre-approval) to the most vulnerable? if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it. The full equation is: P(death+injury|vaccine) < P(death|covid) Before widespread testing, you don't know the severity of a treatment's side effects, especially in vulnerable subpopulations like children and elderly. The risk of severe complications for a novel drug are especially of concern when the immune system is involved, since it's often unstable or senescent in early and late age groups, and overreaction (e.g. cytokine storms) may prove toxic. You don't want the cure to be worse than the disease unless the untreated mortality rate is sky high and no other therapy is viable, as it is for many cancers. In the case of Covid, with a 2-10% death rate (depending on age and region), such desperate measures are hard to justify, especially in low risk groups, until risk of injury is better known.
- marcosdumay 6y ago
  Isn't safety the result of phase II tests? Weren't those complete in June for those vaccines that are getting deployed now? And, anyway, I'm sure getting safety data from a large scale trial, where every vaccinated person is a data point is much faster than getting effectivity data, where only the people exposed to the virus count. Shouldn't vaccines made with proven technology carry a somewhat high prior of efficacy? (And, anyway, with all those problems people are finding on the trials, we are still green lighting them. What's only fair, because it's very likely that the problems aren't important. But why can we make that calculation now, but couldn't in June?)
  - randcraw 6y ago
    Safety is the primary purpose of P2, but the size of those trials is often still too small (often 100 to 500) to detect rarer toxicity events, especially in secondary groups often excluded (e.g. juveniles) in trials that initially target a different primary group (e.g. old folks) for approval. Many drugs fail due to toxicity only during/after P3 when the number of subjects (often 1000 to 30,000) is sufficient to engage sufficient contraindication factors and power needed statistics to reveal detail in the edge cases.
deleted 6y ago
[deleted]
fauigerzigerk 6y ago
>if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it. No, it would have to be P(death|vaccine) < P(death|covid) * P(covid) because not everyone would get covid during the pre-approval period. That's a far higher bar. Also, let's not forget P(covid|vaccine). People would behave very differently once they had the vaccine and feel safe. So if the vaccine isn't effective, that could be catastrophic.
- barnacled 6y ago
  That's a very good point, latter should be P(death ^ covid) I suppose! I still think the numbers would arguably work out well given the general safety especially of the mRNA vaccines (as I understand it). It wouldn't be a simple or easy decision but it's one that should be considered (very carefully!)

odnes 6y ago

> An issue that I basically never see come up is - why not administer the vaccine earlier on (pre-approval) to the most vulnerable? if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it. Not sure, but I would think it comes down to hospitals not being overrun in the case of a widescale negative response to the vaccine. But since the whole thing is a game of probabilities, I do share your view.

barnacled 6y ago
You could distribute it in limited batches to only the most vulnerable which should reduce any risk of that. I think the most vulnerable are in any case most likely to already be heavily using the health services anyway (and would be the ones engaging them the most if they caught the virus).
hef19898 6y ago
Because of ethics in drug development. And these rules are there for a reason. Not sure what could have been done better with Covid vaccines, we have three now roughly a year after the first cases. All of them work and are either certified or on the track to soon be. We even have four if you include the Russian one. Summing up the ethics part: Studies include volunteers in a controlled environment. Just administering un approved stuff to people means using people as guinea pigs. I don't want that, and it is doubtful we would have gained anything. Because now it is "simple" distribution and production problem.
- barnacled 6y ago
  'Because of ethics' and 'these rules are there for a reason' are not arguments, they're 'shut up' encoded. Present arguments please. The progress of the vaccine has been incredible compared to usual, but that doesn't mean more could have been done. Every death is a tragedy. People are constantly used as guinea pigs... as long as there is informed consent as per the Nuremberg code it's fine. Not suggesting anybody would be forced or ill-informed. So back to my argument - you can make a reasonable guess at estimating P(death|vaccine) vs. P(death|covid) and set a big margin, then offer people to VOLUNTARILY agree to take it who are most at risk of dying. The average age of death in the UK is 82 mostly with co-morbidities. I am sure many of these dead would have been happy to take the chance. And in the case of the mRNA vaccines this not some trivial difference - some were developed within weeks/months, but took nearly a year longer to pass all testing. It's really obvious that pandemics need different handling than the 'lock down and loads of people die anyway, both from the virus and the consequences of lockdown while ruining the economy + wait 2yrs for a vaccine to be fully distributed' approach we've got. I hope lessons are learned from covid (I'm actually optimistic they will be, in countries other than the one where the virus emerged anyway).
  - hef19898 6y ago
    > I am sure ... many would have taken the chances So you never asked anyone. The problem is, if you ignore ethics, which of course says a lot about your priorities, still two fold. First, you have development. That was arguably the fastest vaccine development in history. Not sure what could have been done faster here. Second, you have production and distribution. Ramping up these two doesn't make much sense before you know whether or not the vaccines work. Now they are ramped up really fast. Going "fast and breaking" things may have resulted in more people being vaccinated early on. But this small benefit would have caused tremendous issues in a couple of weeks / months. The goal is to get millions vaccinated, not just a few elderly so that some people can go out partying again without feeling bad.
    - barnacled 6y ago
      >So you never asked anyone. The problem is, if you ignore ethics, which of course says a lot about your priorities, still two fold. This is offensive and I suggest you re-read my post (as well as the HN comment guidelines). I am not ignoring ethics, I specifically mention informed consent. I also have no idea what you mean by 'so you never asked anyone' - this is a hypothetical?? >The goal is to get millions vaccinated, not just a few elderly so that some people can go out partying again without feeling bad. You're also strawmanning me pretty hard here. > But this small benefit would have caused tremendous issues in a couple of weeks / months. Not even sure how you come to this conclusion (you seem 100% certain that distributing the now-proven safe mRNA vaccine early would have caused tremendous issues, somehow). You seem to want to be aggressive to me and strawman me as somebody who doesn't care about covid victims (my grandmother is 85 and has serious comorbidity risks thank you very much) so I am not going to respond further but I suggest you focus on arguments, not insults and dismissive comments. You can go to reddit and much of the rest of the internet for that.

BlackVanilla 6y ago

> why not administer the vaccine earlier on (pre-approval) to the most vulnerable? The issue is less tangible and less quantative that that. It's about trust and public buy-in. If vaccine is rolled out despite not fully understanding its efficacy and safety and there are even minor side-effects, there will be fewer people who take the vaccine when they are asked to do so.

barnacled 6y ago
At the cost of how many lives? And if the vaccine is successful how would that harm buy-in? If not then it's a failed experiment (though obviously the PR impact could be rather negative!) I think it's pretty clear from the past year that we need different tools and approaches to dealing with pandemics. One part is clearly faster vaccine development (mRNA seems very promising for this) and pre-emptive vaccine development, another might be permitting very much informed consent take up early on.
- dazzawazza 6y ago
  The cost of a dangerous vaccine could be one hundred years of lower uptake of ALL vaccines decimating the populations of nearly every country in the world. Not worth the risk if you ask me.
  - barnacled 6y ago
    I'm not sure a small subset having a bad reaction to a known-untested vaccine they volunteered to have would have quite as bad an impact as you say, certainly not 100 years of lower uptake! It would likely have some kind of an impact though, and give fuel to anti-vaxxer types (yuk) but I am not sure the impact would be quite so severe.

randcraw 6y ago

[...] why not administer the vaccine earlier on (pre-approval) to the most vulnerable? if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it. The full equation is: P(death+injury|vaccine) < P(death|covid) Before widespread testing, you don't know the severity of a treatment's side effects, especially in vulnerable subpopulations like children and elderly. The risk of severe complications for a novel drug are especially of concern when the immune system is involved, since it's often unstable or senescent in early and late age groups, and overreaction (e.g. cytokine storms) may prove toxic. You don't want the cure to be worse than the disease unless the untreated mortality rate is sky high and no other therapy is viable, as it is for many cancers. In the case of Covid, with a 2-10% death rate (depending on age and region), such desperate measures are hard to justify, especially in low risk groups, until risk of injury is better known.

marcosdumay 6y ago
Isn't safety the result of phase II tests? Weren't those complete in June for those vaccines that are getting deployed now? And, anyway, I'm sure getting safety data from a large scale trial, where every vaccinated person is a data point is much faster than getting effectivity data, where only the people exposed to the virus count. Shouldn't vaccines made with proven technology carry a somewhat high prior of efficacy? (And, anyway, with all those problems people are finding on the trials, we are still green lighting them. What's only fair, because it's very likely that the problems aren't important. But why can we make that calculation now, but couldn't in June?)
- randcraw 6y ago
  Safety is the primary purpose of P2, but the size of those trials is often still too small (often 100 to 500) to detect rarer toxicity events, especially in secondary groups often excluded (e.g. juveniles) in trials that initially target a different primary group (e.g. old folks) for approval. Many drugs fail due to toxicity only during/after P3 when the number of subjects (often 1000 to 30,000) is sufficient to engage sufficient contraindication factors and power needed statistics to reveal detail in the edge cases.

deleted 6y ago

[deleted]

fauigerzigerk 6y ago

>if P(death|vaccine) < P(death|covid) then it seems really barbaric not to give it. No, it would have to be P(death|vaccine) < P(death|covid) * P(covid) because not everyone would get covid during the pre-approval period. That's a far higher bar. Also, let's not forget P(covid|vaccine). People would behave very differently once they had the vaccine and feel safe. So if the vaccine isn't effective, that could be catastrophic.

barnacled 6y ago
That's a very good point, latter should be P(death ^ covid) I suppose! I still think the numbers would arguably work out well given the general safety especially of the mRNA vaccines (as I understand it). It wouldn't be a simple or easy decision but it's one that should be considered (very carefully!)