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It seems to be an underappreciated point that the only alternative to challenge trials is to wait long enough for a sufficient proportion of the vaccine and con

It seems to be an underappreciated point that the only alternative to challenge trials is to wait long enough for a sufficient proportion of the vaccine and control groups to be "naturally" exposed to the virus. You can either intentionally expose volunteers to the virus with X% probability, or send them back into the world and wait for X% of them to be infected. You aren't preventing infections by forbidding challenge trials; all you're doing is allowing millions more people to become infected while you wait for results.

StavrosK 6y ago
You're assuming that pulling or not pulling the lever is morally irrelevant, which may not be the case. To take it to the extreme, it's the difference between killing three people or waiting for three people to die so you can study them. In the former case, you're definitely causing excess infections (some of which might die, directly due to you).
- martincmartin 6y ago
  What if it's killing 3 people, vs waiting for 3,000 to die? What if it's having a small but non-zero probability of killing 1 person, who understands and accepts the risk, vs waiting for thousands to die who really don't want to?
  - StavrosK 6y ago
    Indeed, and apparently ethics boards find it preferable to wait for hundreds of thousands to die rather than kill one, but it's not entirely unreasonable. Also, I think the number of total deaths in both branches are about the same, as they're only waiting for 100ish people to get infected on either arm.
    - xyzzyz 6y ago
      It was entirely unreasonable, though. Also, I think the number of total deaths in both branches are about the same, as they're only waiting for 100ish people to get infected on either arm. When you (entirely unreasonably) restrict your analysis only to the experiment subjects, it is true. However, the vaccine trials cannot be analyzed in a vacuum: the whole reason why these are even a thing is the raging pandemic that kills thousands of people every single day. To put it in a trolley analogy, the decision is not between high speed and low speed trolley that will end up rolling over the same number of people. Instead, in the other branch, in addition to one slow speed trolley, there are also thousands of extra trolleys that you just aren’t explicitly aware of, but they will roll over their victims nonetheless.
      - bawolff 6y ago
        That seems to be torturing the trolly metaphor quite a bit when the original works perfectly fine (actually better) for this situation.
      - bluGill 6y ago
        There is more than that though. Sure with a challenge trial you know that the vaccine works much faster. However you still need to vaccinate tens of thousands and then watch them for a few months to ensure that nothing else bad happens. At least one covid vaccine trails has already failed because the vaccine wasn't safe (in the case I know of because you show up HIV+ even months latter which makes those tests worthless - the vaccine might have worked against Covid for all I know). There have been a lot of other vaccines trials over the years that have failed for safety reasons.
        xyzzyz 6y ago
        > At least one covid vaccine trails has already failed because the vaccine wasn't safe (in the case I know of because you show up HIV+ even months latter which makes those tests worthless - the vaccine might have worked against Covid for all I know). That may be a good enough to nix development for common cold vaccine, but how can one argue that it’s serious enough problem to cancel vaccine for disease that kills thousands of people every single day? This is another example of how “safety” and “ethics” regulations have little to do, and in fact are counterproductive to achieve safety and ethics in real world.
        mattkrause 6y ago
        It was clear at the time that other vaccine candidates were working at least as well: Pfizer/Bio-NTech got its EUA the same week AND didn’t mess up HIV tests. Seems like a pretty straightforward decision to me. https://www.nature.com/articles/d41586-020-03570-0 https://www.nature.com/articles/d41586-020-03570-0
  - bluGill 6y ago
    What if the 3000 don't die though. At any time covid could hit some sort of natural limit and stop spreading (as happened to SARS before it). At anytime we could discover a miracle cure that means Covid isn't a problem (as antibiotics did for infections). Since you don't know about those unknowns it is hard to say in advance if you killed 3 so 2997 could live, or killed 3 people for nothing.
- waterhouse 6y ago
  But it's not you that's killing the test subjects; they're doing it to themselves. (Well, it depends on the experimental setup, but it can be easily arranged that way: you could leave a spray bottle on the table and tell them "This contains the coronavirus. If you spray your face with it, you will help our experiment, but risk death. You are also free to just go home and face no consequences.") I don't understand the argument for moral relevance.
  - statstutor 6y ago
    Edited: "This contains the coronavirus. If you spray your face with it, we will give you money enough to pay a month or two's rent and living expenses, but you risk your death. You are also free to just leave."
- esotericn 6y ago
  Taking a top-level view though, we've pulled about a billion different levers. In the UK we've restricted the activity of healthy individuals for about 11 months now - the latest episode being an approximately 3 month period within which it's illegal to meet anyone else within your own home. Psychological trials, even trivial things like filling in surveys or taking reaction speed tests are carefully monitored for ethical concerns, lockdown we just went all in on with no cost-benefit analysis. It seems bizarre to me that in that context we should be worrying about the ethics of a challenge study with a few hundred or few thousand volunteers. Loads of people I know have _already_ volunteered themselves for it in the outside world with no compensation and with no benefit to science because they're not able to mentally handle indefinite restrictions.
folli 6y ago
Interesting point of view, but where would you set the threshold: a challenge trial for a cancer drug by injecting a carcinogen to cause tumor growth? What about viral diseases that are much more devastating, e.g. a challenge study for an ebola vaccine?
- waterhouse 6y ago
  There are no ethical issues when the subjects are fully willing volunteers who have had the risks properly explained and emphasized to them. As some have mentioned, if people can volunteer to risk their own life for the army, then why not for this? (The experiment must, of course, fully quarantine the volunteers who are given an infectious disease (cancer is not infectious, ebola is) until they're recovered (or dead); otherwise they'd be risking more than just the volunteers' lives.)
  - refurb 6y ago
    There are ethical issues. You’re just not aware of them. Do you compensate the participants for their time? If not, can you find enough people to run the trial? If you do compensate them are they truly consenting freely? Or do they just need the money? Consent is a very complicated issue and you’re hand waving all the nuances away.
    - waterhouse 6y ago
      I do think it's a silly argument that paying someone to do something means they're not freely consenting to do the thing. As long as it's not your fault that they're in a bad economic situation, all you're doing is offering them an option that they, by accepting it, believe to be an improvement over their current situation. People who don't like sweatshops should be removing all barriers to the setting up of more sweatshops, so that they will compete for workers and eventually have to improve working conditions or raise wages. However, in this case, I suspect offering a monetary incentive wouldn't be necessary. Everyone knows about the terrible disease; just make a patriotic appeal and I expect you'd have plenty of unpaid volunteers.
learnstats2 6y ago
This is being reported as if the challenge trial is giving people already-approved vaccines (also note the first stage of the trial is not even doing that step). As such, the benefit of deliberately infecting people over waiting for natural exposure appears to me to be zero.

StavrosK 6y ago

You're assuming that pulling or not pulling the lever is morally irrelevant, which may not be the case. To take it to the extreme, it's the difference between killing three people or waiting for three people to die so you can study them. In the former case, you're definitely causing excess infections (some of which might die, directly due to you).

martincmartin 6y ago
What if it's killing 3 people, vs waiting for 3,000 to die? What if it's having a small but non-zero probability of killing 1 person, who understands and accepts the risk, vs waiting for thousands to die who really don't want to?
- StavrosK 6y ago
  Indeed, and apparently ethics boards find it preferable to wait for hundreds of thousands to die rather than kill one, but it's not entirely unreasonable. Also, I think the number of total deaths in both branches are about the same, as they're only waiting for 100ish people to get infected on either arm.
  - xyzzyz 6y ago
    It was entirely unreasonable, though. Also, I think the number of total deaths in both branches are about the same, as they're only waiting for 100ish people to get infected on either arm. When you (entirely unreasonably) restrict your analysis only to the experiment subjects, it is true. However, the vaccine trials cannot be analyzed in a vacuum: the whole reason why these are even a thing is the raging pandemic that kills thousands of people every single day. To put it in a trolley analogy, the decision is not between high speed and low speed trolley that will end up rolling over the same number of people. Instead, in the other branch, in addition to one slow speed trolley, there are also thousands of extra trolleys that you just aren’t explicitly aware of, but they will roll over their victims nonetheless.
    - bawolff 6y ago
      That seems to be torturing the trolly metaphor quite a bit when the original works perfectly fine (actually better) for this situation.
    - bluGill 6y ago
      There is more than that though. Sure with a challenge trial you know that the vaccine works much faster. However you still need to vaccinate tens of thousands and then watch them for a few months to ensure that nothing else bad happens. At least one covid vaccine trails has already failed because the vaccine wasn't safe (in the case I know of because you show up HIV+ even months latter which makes those tests worthless - the vaccine might have worked against Covid for all I know). There have been a lot of other vaccines trials over the years that have failed for safety reasons.
      - xyzzyz 6y ago
        > At least one covid vaccine trails has already failed because the vaccine wasn't safe (in the case I know of because you show up HIV+ even months latter which makes those tests worthless - the vaccine might have worked against Covid for all I know). That may be a good enough to nix development for common cold vaccine, but how can one argue that it’s serious enough problem to cancel vaccine for disease that kills thousands of people every single day? This is another example of how “safety” and “ethics” regulations have little to do, and in fact are counterproductive to achieve safety and ethics in real world.
        mattkrause 6y ago
        It was clear at the time that other vaccine candidates were working at least as well: Pfizer/Bio-NTech got its EUA the same week AND didn’t mess up HIV tests. Seems like a pretty straightforward decision to me. https://www.nature.com/articles/d41586-020-03570-0 https://www.nature.com/articles/d41586-020-03570-0
- bluGill 6y ago
  What if the 3000 don't die though. At any time covid could hit some sort of natural limit and stop spreading (as happened to SARS before it). At anytime we could discover a miracle cure that means Covid isn't a problem (as antibiotics did for infections). Since you don't know about those unknowns it is hard to say in advance if you killed 3 so 2997 could live, or killed 3 people for nothing.
waterhouse 6y ago
But it's not you that's killing the test subjects; they're doing it to themselves. (Well, it depends on the experimental setup, but it can be easily arranged that way: you could leave a spray bottle on the table and tell them "This contains the coronavirus. If you spray your face with it, you will help our experiment, but risk death. You are also free to just go home and face no consequences.") I don't understand the argument for moral relevance.
- statstutor 6y ago
  Edited: "This contains the coronavirus. If you spray your face with it, we will give you money enough to pay a month or two's rent and living expenses, but you risk your death. You are also free to just leave."
esotericn 6y ago
Taking a top-level view though, we've pulled about a billion different levers. In the UK we've restricted the activity of healthy individuals for about 11 months now - the latest episode being an approximately 3 month period within which it's illegal to meet anyone else within your own home. Psychological trials, even trivial things like filling in surveys or taking reaction speed tests are carefully monitored for ethical concerns, lockdown we just went all in on with no cost-benefit analysis. It seems bizarre to me that in that context we should be worrying about the ethics of a challenge study with a few hundred or few thousand volunteers. Loads of people I know have _already_ volunteered themselves for it in the outside world with no compensation and with no benefit to science because they're not able to mentally handle indefinite restrictions.

folli 6y ago

Interesting point of view, but where would you set the threshold: a challenge trial for a cancer drug by injecting a carcinogen to cause tumor growth? What about viral diseases that are much more devastating, e.g. a challenge study for an ebola vaccine?

waterhouse 6y ago
There are no ethical issues when the subjects are fully willing volunteers who have had the risks properly explained and emphasized to them. As some have mentioned, if people can volunteer to risk their own life for the army, then why not for this? (The experiment must, of course, fully quarantine the volunteers who are given an infectious disease (cancer is not infectious, ebola is) until they're recovered (or dead); otherwise they'd be risking more than just the volunteers' lives.)
- refurb 6y ago
  There are ethical issues. You’re just not aware of them. Do you compensate the participants for their time? If not, can you find enough people to run the trial? If you do compensate them are they truly consenting freely? Or do they just need the money? Consent is a very complicated issue and you’re hand waving all the nuances away.
  - waterhouse 6y ago
    I do think it's a silly argument that paying someone to do something means they're not freely consenting to do the thing. As long as it's not your fault that they're in a bad economic situation, all you're doing is offering them an option that they, by accepting it, believe to be an improvement over their current situation. People who don't like sweatshops should be removing all barriers to the setting up of more sweatshops, so that they will compete for workers and eventually have to improve working conditions or raise wages. However, in this case, I suspect offering a monetary incentive wouldn't be necessary. Everyone knows about the terrible disease; just make a patriotic appeal and I expect you'd have plenty of unpaid volunteers.

learnstats2 6y ago

This is being reported as if the challenge trial is giving people already-approved vaccines (also note the first stage of the trial is not even doing that step). As such, the benefit of deliberately infecting people over waiting for natural exposure appears to me to be zero.