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I agree. The Moderna vaccine was created in a weekend, it took many months to run trials in a way that compiled with bioethicist diktat to prove efficacy . The

by tyho 6y ago

I agree. The Moderna vaccine was created in a weekend, it took many months to run trials in a way that compiled with bioethicist diktat to prove efficacy . The limiting factor in the speed of the clinical trials is the rate at which people acquire COVID naturally. During the summer there were serious worries that the vaccine trials would fail due to low transmission rates. Had the clinical trials run in a "less ethical" way, say by taking young and healthy people like myself, vaccinating them and then deliberately exposing them to COVID, then we might have seen vaccination start much sooner. Far fewer would have died and the colossal impact of lockdowns would have been mostly avoided.

oldgradstudent 6y ago
> Had the clinical trials run in a "less ethical" way, say by taking young and healthy people like myself And what exactly would that have told you about the safety and effectiveness of the vaccine for the people at risk, those who are neither young nor healthy? And how many people would you need to challenge to show that the vaccine prevents deaths or even serious disease? The young and healthy rarely get the full brunt of the disease.
- ericb 6y ago
  You can still measure: the immune response, antibodies, white blood cells, scenarios in which the contagion can spread, minimal social distance needed, length of exposure required for transmission, how much masks stop transmission, safety (risk reduction), and peak efficacy. You can do it on a much shorter timescale, and with fewer lives lost. What if we had needed to iterate to fix problems in the vaccine? How many would die waiting? To your specific question, you still derisk it for the elderly. If it causes problems in young adults, you quit because it would probably cause even more problems in riskier groups. If it doesn't, you move forward into older groups. Let's not pretend you would learn nothing that would speed things along. Some of these questions aren't answered quantitatively even now.
  - oldgradstudent 6y ago
    > You can still measure: the immune response, antibodies, white blood cells, scenarios in which the contagion can spread, minimal social distance needed, length of exposure required for transmission, how much masks stop transmission, safety (risk reduction), and peak efficacy. [...] Of course. These are all great uses for challenge studies, I was responding specifically to testing the vaccine using a challenge study on healthy young adults. > If it causes problems in young adults, you quit because it would probably cause even more problems in riskier groups. If it doesn't, you move forward into older groups. It turns out that both Pfizer and Moderna trials have shown much more adverse reactions in the young than the old. Testing on the wrong population may result in rejecting a vaccine that could be perfectly safe on the at-risk population, but inappropriate for the general population. > Let's not pretend you would learn nothing that would speed things along Of course not. You could learn a lot, just not about the safety and efficacy profile of the vaccine on the at-risk population.
- mjmahone17 6y ago
  > And what exactly would that have told you about the safety and effectiveness of the vaccine for the people at risk, those who are neither young nor healthy? So if the goal was to reduce transmission, you can save a lot of lives of those at risk by vaccinating the young and healthy. It would be reasonable to basically use challenge studies to get a lower transmission rate, while in parallel using standard trials to prove the efficacy in at risk populations. Getting more data quicker is usually a good way to make more informed decisions, even if the data isn’t exactly what you want it to be to make the perfectly optimal choices.
  - runako 6y ago
    > So if the goal was to reduce transmission, you can save a lot of lives of those at risk by vaccinating the young and healthy. Has this been tested yet? Is there evidence that this is true beyond the broad population surveys like those from Israel? (The accuracy of those data were hotly debated here last week.) Surely a study to determine actual transmission rates would be much more complex than one to determine whether young & healthy people are infected after inoculation (which again: not that useful of a data point by itself)?
    - Closi 6y ago
      Well transmission effectiveness is a good example of something that’s much easier to measure in a controlled challenge study and almost impossible to measure pre-rollout without it!
      - runako 6y ago
        How? The vaccinated individuals would come into contact with lots of people who are not vaccinated. How do you track all of them to determine if vaccinated individuals can transmit the disease? That seems like a much larger logistical problem that differs from the existing (and challenge) trials in very material ways.
        Closi 6y ago
- maxerickson 6y ago
  Administering a vaccine that is only effective in young healthy people to young healthy people makes everyone safer. And that's the bad outcome where the slower trials in more at risk people don't work out. In the good outcome, when you decide it is safe and effective in vulnerable people, production and administration have already been scaled out. (could study viral load in a challenge trial where you don't have to test thousands of uninfected people to find asymptomatic cases…)
- this_user 6y ago
  The important thing is that these trials can only be performed on the young and healthy who are at the least risk of severe illness and death. This means any results gained from these would have been essentially worthless when it comes to the patients most at risk. Consequently, one would have still had to run the regular P3 trials with a diverse group of subjects. Therefore, any acceleration in the vaccine's development process would have at best been marginal. This is also what the industry association of German drug manufacturers has pointed out in a statement, dismissing the British challenge trials as ethically dubious and effectively useless.
TamDenholm 6y ago
Not disagreeing with you at all, but this has a parallel with the age old hypothetical questions that people regularly ask each other. Would you kill 1 person to save 100 people? I don't think theres even a correct answer, its all opinion. Having no knowledge of the field of ethicists, i would imagine that these are the kinds of things they debate all day long, theres a million variations on the same question.
- Jabbles 6y ago
  Surely the general question doesn't matter though, and all the millions of variations are irrelevant, as there is a specific example that you want to consider.
- defen 6y ago
  In this case it's more like "would you allow a group of 18-20 year olds to voluntarily deliberately expose themselves to the same risk of death presented by driving 7,500 miles in order to save the lives of a million people?"
- deleted 6y ago
  [deleted]
DiogenesKynikos 6y ago
You're skipping over the safety aspect of phase-1/2/3 trials. In your proposed accelerated schedule, would we just throw safety testing out the window? > The limiting factor in the speed of the clinical trials is the rate at which people acquire COVID naturally. That's only one of the factors. It takes weeks to go from infection to disease outcome. If you're also interested in safety, you have to enroll tens of thousands of people, give them the vaccine, and wait to see if there are side-effects. And of course, you have to scale up production. In the grand scheme of things, the wait for people to get naturally infected in phase-3 trials was relatively short (a few weeks). > Far fewer would have died and the colossal impact of lockdowns would have been mostly avoided. Countries that had extremely strict lockdowns were able to reopen nearly completely with extremely low virus prevalence, and then to control the virus with good tracing. China has been mostly open since last spring, and fewer than 5000 people have died in total in the country (almost all of them in the first 3 months of the outbreak).
- tinus_hn 6y ago
  One has to compare the risks of not testing against the risk of testing. We can now tell that testing, up to now, results in over 2 million deaths. What would the risks have been for not testing?
  - mattkrause 6y ago
    I can’t even begin to imagine how you’d calculate that. We’ve got some vaccines that work, a few that don’t, and at least one candidate that looked promising but was abandoned for problematic side effects (false-positives on HIV tests). You can’t just divide those out though, because all of this work was done in systems where people expected thorough testing. In a world where we didn’t test, the ”honest” attempts might not be as careful and there would also be a number of outright scams.
    - tinus_hn 6y ago
      Right, so the people who voluntarily chose to take this risk would be exposed to the risk. Of testing false positive for HIV. How does this not beat 2 million deaths?
pcrh 6y ago
>The Moderna vaccine was created in a weekend On the face of it, this is an uninformed opionion, whether or not it was "created in weekend" or not.
- tinus_hn 6y ago
  So if it was created in a weekend, the statement that it was created in a weekend is an uninformed opinion? On the face of it, I would call it the truth.
  - dmlerner 6y ago
    It was "created in a weekend" like I might get this quarter's big new API done in a weekend. Still gotta test, document, bicker over variable names, etc. I imagine "created" is as small a fraction of vaccine development as prototyping code is of software engineering. As to say, not very "created in a weekend."
    - tinus_hn 6y ago
      Like, after a weekend it existed. Very much ‘created in a weekend.’ It’s a choice whether you do a year long three phase trial. Or not. The vaccine (recipe) still exists.
dragonwriter 6y ago
> The Moderna vaccine was created in a weekend I may have misremembered slightly but I seem to recall 42 days fromm sequence identification, leveraging a roughly 10-year project related to related coronavirus work (MERS). So, not exactly a weekend. Also, there were several candidates developed in parallel, but others failed at various trial stages. Less effective testing (and your proposal is less effective, both for safety and efficacy) might mean people get vaccines sooner, but it also means they get less effective and more dangerous vaccines sooner, meaning more people die of vaccines (bad for first order effects, and worse for the second order effect of increasing public vaccine reluctance) and that instead of stopping spread by vaccination we increase the selective pressure for diverse, resistant new variants without doing so.
refurb 6y ago
You realize that the vaccines aren’t approved for children under 16 because there weren’t any in the trial. How would a challenge trial in health 20-30 year olds help when most of the people dying are over 70? Do you just wave your hands and extrapolate?

by tyho 6y ago

oldgradstudent 6y ago

> Had the clinical trials run in a "less ethical" way, say by taking young and healthy people like myself And what exactly would that have told you about the safety and effectiveness of the vaccine for the people at risk, those who are neither young nor healthy? And how many people would you need to challenge to show that the vaccine prevents deaths or even serious disease? The young and healthy rarely get the full brunt of the disease.

ericb 6y ago
You can still measure: the immune response, antibodies, white blood cells, scenarios in which the contagion can spread, minimal social distance needed, length of exposure required for transmission, how much masks stop transmission, safety (risk reduction), and peak efficacy. You can do it on a much shorter timescale, and with fewer lives lost. What if we had needed to iterate to fix problems in the vaccine? How many would die waiting? To your specific question, you still derisk it for the elderly. If it causes problems in young adults, you quit because it would probably cause even more problems in riskier groups. If it doesn't, you move forward into older groups. Let's not pretend you would learn nothing that would speed things along. Some of these questions aren't answered quantitatively even now.
- oldgradstudent 6y ago
  > You can still measure: the immune response, antibodies, white blood cells, scenarios in which the contagion can spread, minimal social distance needed, length of exposure required for transmission, how much masks stop transmission, safety (risk reduction), and peak efficacy. [...] Of course. These are all great uses for challenge studies, I was responding specifically to testing the vaccine using a challenge study on healthy young adults. > If it causes problems in young adults, you quit because it would probably cause even more problems in riskier groups. If it doesn't, you move forward into older groups. It turns out that both Pfizer and Moderna trials have shown much more adverse reactions in the young than the old. Testing on the wrong population may result in rejecting a vaccine that could be perfectly safe on the at-risk population, but inappropriate for the general population. > Let's not pretend you would learn nothing that would speed things along Of course not. You could learn a lot, just not about the safety and efficacy profile of the vaccine on the at-risk population.
mjmahone17 6y ago
> And what exactly would that have told you about the safety and effectiveness of the vaccine for the people at risk, those who are neither young nor healthy? So if the goal was to reduce transmission, you can save a lot of lives of those at risk by vaccinating the young and healthy. It would be reasonable to basically use challenge studies to get a lower transmission rate, while in parallel using standard trials to prove the efficacy in at risk populations. Getting more data quicker is usually a good way to make more informed decisions, even if the data isn’t exactly what you want it to be to make the perfectly optimal choices.
- runako 6y ago
  > So if the goal was to reduce transmission, you can save a lot of lives of those at risk by vaccinating the young and healthy. Has this been tested yet? Is there evidence that this is true beyond the broad population surveys like those from Israel? (The accuracy of those data were hotly debated here last week.) Surely a study to determine actual transmission rates would be much more complex than one to determine whether young & healthy people are infected after inoculation (which again: not that useful of a data point by itself)?
  - Closi 6y ago
    Well transmission effectiveness is a good example of something that’s much easier to measure in a controlled challenge study and almost impossible to measure pre-rollout without it!
    - runako 6y ago
      How? The vaccinated individuals would come into contact with lots of people who are not vaccinated. How do you track all of them to determine if vaccinated individuals can transmit the disease? That seems like a much larger logistical problem that differs from the existing (and challenge) trials in very material ways.
      - Closi 6y ago
maxerickson 6y ago
Administering a vaccine that is only effective in young healthy people to young healthy people makes everyone safer. And that's the bad outcome where the slower trials in more at risk people don't work out. In the good outcome, when you decide it is safe and effective in vulnerable people, production and administration have already been scaled out. (could study viral load in a challenge trial where you don't have to test thousands of uninfected people to find asymptomatic cases…)
this_user 6y ago
The important thing is that these trials can only be performed on the young and healthy who are at the least risk of severe illness and death. This means any results gained from these would have been essentially worthless when it comes to the patients most at risk. Consequently, one would have still had to run the regular P3 trials with a diverse group of subjects. Therefore, any acceleration in the vaccine's development process would have at best been marginal. This is also what the industry association of German drug manufacturers has pointed out in a statement, dismissing the British challenge trials as ethically dubious and effectively useless.

TamDenholm 6y ago

Not disagreeing with you at all, but this has a parallel with the age old hypothetical questions that people regularly ask each other. Would you kill 1 person to save 100 people? I don't think theres even a correct answer, its all opinion. Having no knowledge of the field of ethicists, i would imagine that these are the kinds of things they debate all day long, theres a million variations on the same question.

Jabbles 6y ago
Surely the general question doesn't matter though, and all the millions of variations are irrelevant, as there is a specific example that you want to consider.
defen 6y ago
In this case it's more like "would you allow a group of 18-20 year olds to voluntarily deliberately expose themselves to the same risk of death presented by driving 7,500 miles in order to save the lives of a million people?"
deleted 6y ago
[deleted]

DiogenesKynikos 6y ago

You're skipping over the safety aspect of phase-1/2/3 trials. In your proposed accelerated schedule, would we just throw safety testing out the window? > The limiting factor in the speed of the clinical trials is the rate at which people acquire COVID naturally. That's only one of the factors. It takes weeks to go from infection to disease outcome. If you're also interested in safety, you have to enroll tens of thousands of people, give them the vaccine, and wait to see if there are side-effects. And of course, you have to scale up production. In the grand scheme of things, the wait for people to get naturally infected in phase-3 trials was relatively short (a few weeks). > Far fewer would have died and the colossal impact of lockdowns would have been mostly avoided. Countries that had extremely strict lockdowns were able to reopen nearly completely with extremely low virus prevalence, and then to control the virus with good tracing. China has been mostly open since last spring, and fewer than 5000 people have died in total in the country (almost all of them in the first 3 months of the outbreak).

tinus_hn 6y ago
One has to compare the risks of not testing against the risk of testing. We can now tell that testing, up to now, results in over 2 million deaths. What would the risks have been for not testing?
- mattkrause 6y ago
  I can’t even begin to imagine how you’d calculate that. We’ve got some vaccines that work, a few that don’t, and at least one candidate that looked promising but was abandoned for problematic side effects (false-positives on HIV tests). You can’t just divide those out though, because all of this work was done in systems where people expected thorough testing. In a world where we didn’t test, the ”honest” attempts might not be as careful and there would also be a number of outright scams.
  - tinus_hn 6y ago
    Right, so the people who voluntarily chose to take this risk would be exposed to the risk. Of testing false positive for HIV. How does this not beat 2 million deaths?

pcrh 6y ago

>The Moderna vaccine was created in a weekend On the face of it, this is an uninformed opionion, whether or not it was "created in weekend" or not.

tinus_hn 6y ago
So if it was created in a weekend, the statement that it was created in a weekend is an uninformed opinion? On the face of it, I would call it the truth.
- dmlerner 6y ago
  It was "created in a weekend" like I might get this quarter's big new API done in a weekend. Still gotta test, document, bicker over variable names, etc. I imagine "created" is as small a fraction of vaccine development as prototyping code is of software engineering. As to say, not very "created in a weekend."
  - tinus_hn 6y ago
    Like, after a weekend it existed. Very much ‘created in a weekend.’ It’s a choice whether you do a year long three phase trial. Or not. The vaccine (recipe) still exists.

dragonwriter 6y ago

> The Moderna vaccine was created in a weekend I may have misremembered slightly but I seem to recall 42 days fromm sequence identification, leveraging a roughly 10-year project related to related coronavirus work (MERS). So, not exactly a weekend. Also, there were several candidates developed in parallel, but others failed at various trial stages. Less effective testing (and your proposal is less effective, both for safety and efficacy) might mean people get vaccines sooner, but it also means they get less effective and more dangerous vaccines sooner, meaning more people die of vaccines (bad for first order effects, and worse for the second order effect of increasing public vaccine reluctance) and that instead of stopping spread by vaccination we increase the selective pressure for diverse, resistant new variants without doing so.

refurb 6y ago

You realize that the vaccines aren’t approved for children under 16 because there weren’t any in the trial. How would a challenge trial in health 20-30 year olds help when most of the people dying are over 70? Do you just wave your hands and extrapolate?