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[...] 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

[...] 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.
  - marcosdumay 6y ago
    What is a reasonable prior for the toxicity of an old tech vaccine (like viral vector, that is reasonably common for COVID) that passed P2? We have been making vaccines for a while, we should be able to answer that. Also, how long do we need to wait on P3 before we get the toxicity result? A really rigorous answer is that we need several years because some problems appear very slowly. Yet, we are not waiting those years. We are declaring definitive success with incomplete information. What is very reasonable, because it is very unlikely that those vaccines will have long term toxicity... but then, why are we using that prior, but refuse to use the P2 or early P3 results to make a temporary decision? Why we decided that it was ok to try the vaccine on 10s of thousands in June, but couldn't expand that number to 100's of thousands on July, or millions by August? The decisions were taken by calgo culting regulations, and caused a lot unnecessary harm.
barnacled 6y ago
In the case of highly vulnerable patients the death rate is vastly higher, easily into the double-digits, e.g. https://www.manchester.ac.uk/discover/news/frailty-old-age-and-comorbidity-main-predictors-of-death-from-covid-19/ https://www.manchester.ac.uk/discover/news/frailty-old-age-a... - with extreme risk factors and old age the death rate is staggering. If you had e.g. a 75% chance of death but the vaccine had a 0.01% chance of killing or seriously impairing you, even taking into account all the issues and the risk of actually catching it the risk seems worthwhile. However this discussion does make me think that the candidate range is going to be pretty narrow, and of course all concerned would have to be able and willing to give informed consent many of whom presumably would not.

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.
- marcosdumay 6y ago
  What is a reasonable prior for the toxicity of an old tech vaccine (like viral vector, that is reasonably common for COVID) that passed P2? We have been making vaccines for a while, we should be able to answer that. Also, how long do we need to wait on P3 before we get the toxicity result? A really rigorous answer is that we need several years because some problems appear very slowly. Yet, we are not waiting those years. We are declaring definitive success with incomplete information. What is very reasonable, because it is very unlikely that those vaccines will have long term toxicity... but then, why are we using that prior, but refuse to use the P2 or early P3 results to make a temporary decision? Why we decided that it was ok to try the vaccine on 10s of thousands in June, but couldn't expand that number to 100's of thousands on July, or millions by August? The decisions were taken by calgo culting regulations, and caused a lot unnecessary harm.

barnacled 6y ago

In the case of highly vulnerable patients the death rate is vastly higher, easily into the double-digits, e.g. https://www.manchester.ac.uk/discover/news/frailty-old-age-and-comorbidity-main-predictors-of-death-from-covid-19/ https://www.manchester.ac.uk/discover/news/frailty-old-age-a... - with extreme risk factors and old age the death rate is staggering. If you had e.g. a 75% chance of death but the vaccine had a 0.01% chance of killing or seriously impairing you, even taking into account all the issues and the risk of actually catching it the risk seems worthwhile. However this discussion does make me think that the candidate range is going to be pretty narrow, and of course all concerned would have to be able and willing to give informed consent many of whom presumably would not.