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> outcomes are normally distributed in severity and time and if you give enough people the vaccine you can substitute that for waiting What an utterly fortunat

> outcomes are normally distributed in severity and time and if you give enough people the vaccine you can substitute that for waiting What an utterly fortunate universal truth of vaccines!

arcticbull 3y ago
It's kind of true when you're looking for the long tail in anything. The reality is most drugs and vaccines that you get are tested on a few hundred or a few thousand people over a long period of time. But mostly because it's very difficult to measure the efficacy of something with statistical significance if the prevalence rate is low. So you can either give a bunch of people Ebola to check if the Ebola vaccine works, or you can wait a long time. Ethics boards frown on the former. However with COVID like 1% of the population had it when we were ready to test vaccines so showing efficacy was very quick and very easy.
- peteradio 3y ago
  But aren't we talking about latent issues? It sounds like you are saying most drugs de-facto check this because the trials must go for so long. But that's the point isn't it? Because short term efficacy was proven so quickly the de-facto check on latent issues never occurred.
  - arcticbull 3y ago
    Let me ask you this. What reason do you or anyone else on earth have to think there would be a mechanism that yields latent issues? We have studied mRNA for about 50 years now. And the adenoviral vector vaccines are a completely different mechanism studied for about 50 years too. What exactly bad thing do you think would miraculously appear 3 years later showing zero signs, symptoms or evidence in 6 billion people? And why would that be different after 5, 10 or even 15 years? There's no law that says Tylenol doesn't cause your arm to fall off 110 years later either, but that's not the standard of proof. Nothing in life has zero risk. That aside I think if your n is large enough, I think even issues that are ordinarily latent would be at least detectable. Certainly 3 years later. The normal development cycle is as short as 5 years, 2 of which are in regulatory approval. At some point we have to be guided by our past experience. You can't ever prove a negative, but you don't have to prove a negative to move forward.
    - peteradio 3y ago
      I'm not really worried about mRNA per-se I'm worried about an unvetted delivery mechanism. Did you know its rare but accepted that some dogs get injection site tumors and we don't really know why? That would surely be a latent effect in dogs, why do we think it could never happen in humans who live much longer?
      - arcticbull 3y ago
        > I'm not really worried about mRNA per-se I'm worried about an unvetted delivery mechanism. mRNA and the adenoviral vector vaccine delivery mechanisms have been studied for 50+ years and are vetted. > Did you know its rare but accepted that some dogs get injection site tumors and we don't really know why? Did you know dogs aren't humans, and there's no evidence of this kind of thing in humans at all? btw it's also extremely extremely rare in dogs, to the extent it's hard to find any kind of data on it. It wasn't thought to occur except in cats until the 70s, so I've written up the rest of this generously assuming cats. Most study headlines you read are fun achievements that only work on the animals under study and they don't have the same effects in humans. You can significantly increase the life of worms by not feeding them, but humans not so much. Weird huh. Again this brings us back to our 'substitution of T with N' conversation. It's always a normal distribution. While these VAS tumors develop a few years in, in some cases they develop within a few months. So if you give 6 billion people vaccines over 3 years, you would have definitely seen this kind of latent thing by now, even if its peak effect is a few years later. > That would surely be a latent effect in dogs, why do we think it could never happen in humans who live much longer? That's not a thing. Again you're asking to prove a negative, which is not how we do anything because it's impossible. The burden of proof is on you to explain why you think it could happen, not on me to prove why it couldn't. Prove to me that eating a tomato won't cause turbo-cancer of the elbow. You can't.
        peteradio 3y ago
        I love the way this progressed from, latent disease doesn't happen to prove to me tomatoes don't cause turbo-cancer. There's so much text there that its really nice and smooth.

> outcomes are normally distributed in severity and time and if you give enough people the vaccine you can substitute that for waiting What an utterly fortunate universal truth of vaccines!

arcticbull 3y ago

It's kind of true when you're looking for the long tail in anything. The reality is most drugs and vaccines that you get are tested on a few hundred or a few thousand people over a long period of time. But mostly because it's very difficult to measure the efficacy of something with statistical significance if the prevalence rate is low. So you can either give a bunch of people Ebola to check if the Ebola vaccine works, or you can wait a long time. Ethics boards frown on the former. However with COVID like 1% of the population had it when we were ready to test vaccines so showing efficacy was very quick and very easy.

peteradio 3y ago
But aren't we talking about latent issues? It sounds like you are saying most drugs de-facto check this because the trials must go for so long. But that's the point isn't it? Because short term efficacy was proven so quickly the de-facto check on latent issues never occurred.
- arcticbull 3y ago
  Let me ask you this. What reason do you or anyone else on earth have to think there would be a mechanism that yields latent issues? We have studied mRNA for about 50 years now. And the adenoviral vector vaccines are a completely different mechanism studied for about 50 years too. What exactly bad thing do you think would miraculously appear 3 years later showing zero signs, symptoms or evidence in 6 billion people? And why would that be different after 5, 10 or even 15 years? There's no law that says Tylenol doesn't cause your arm to fall off 110 years later either, but that's not the standard of proof. Nothing in life has zero risk. That aside I think if your n is large enough, I think even issues that are ordinarily latent would be at least detectable. Certainly 3 years later. The normal development cycle is as short as 5 years, 2 of which are in regulatory approval. At some point we have to be guided by our past experience. You can't ever prove a negative, but you don't have to prove a negative to move forward.
  - peteradio 3y ago
    I'm not really worried about mRNA per-se I'm worried about an unvetted delivery mechanism. Did you know its rare but accepted that some dogs get injection site tumors and we don't really know why? That would surely be a latent effect in dogs, why do we think it could never happen in humans who live much longer?
    - arcticbull 3y ago
      > I'm not really worried about mRNA per-se I'm worried about an unvetted delivery mechanism. mRNA and the adenoviral vector vaccine delivery mechanisms have been studied for 50+ years and are vetted. > Did you know its rare but accepted that some dogs get injection site tumors and we don't really know why? Did you know dogs aren't humans, and there's no evidence of this kind of thing in humans at all? btw it's also extremely extremely rare in dogs, to the extent it's hard to find any kind of data on it. It wasn't thought to occur except in cats until the 70s, so I've written up the rest of this generously assuming cats. Most study headlines you read are fun achievements that only work on the animals under study and they don't have the same effects in humans. You can significantly increase the life of worms by not feeding them, but humans not so much. Weird huh. Again this brings us back to our 'substitution of T with N' conversation. It's always a normal distribution. While these VAS tumors develop a few years in, in some cases they develop within a few months. So if you give 6 billion people vaccines over 3 years, you would have definitely seen this kind of latent thing by now, even if its peak effect is a few years later. > That would surely be a latent effect in dogs, why do we think it could never happen in humans who live much longer? That's not a thing. Again you're asking to prove a negative, which is not how we do anything because it's impossible. The burden of proof is on you to explain why you think it could happen, not on me to prove why it couldn't. Prove to me that eating a tomato won't cause turbo-cancer of the elbow. You can't.
      - peteradio 3y ago
        I love the way this progressed from, latent disease doesn't happen to prove to me tomatoes don't cause turbo-cancer. There's so much text there that its really nice and smooth.