17 ms·

Coronavirus human challenge study gets green light in UK

114 points by timthorn 6y ago

fallingknife 6y ago
Strange that, until this point, the virus has been deemed dangerous enough to shut down whole swathes of the economy for a year, but not dangerous enough to bend the rules of clinical trials to find a vaccine faster. If we had done this sooner, we might have got the vaccine out before the mutant strains appeared over the last couple months.
- whatshisface 6y ago
  The trolley problem solution that gets chosen in real life situations really seems to be a consistent "last person who touched it broke it" policy.
  - dehrmann 6y ago
    Politically, it's the winning solution.
  - jdminhbg 6y ago
    > The Copenhagen Interpretation of quantum mechanics says that you can have a particle spinning clockwise and counterclockwise at the same time – until you look at it, at which point it definitely becomes one or the other. The theory claims that observing reality fundamentally changes it. > The Copenhagen Interpretation of Ethics says that when you observe or interact with a problem in any way, you can be blamed for it. At the very least, you are to blame for not doing more. Even if you don’t make the problem worse, even if you make it slightly better, the ethical burden of the problem falls on you as soon as you observe it. In particular, if you interact with a problem and benefit from it, you are a complete monster. I don’t subscribe to this school of thought, but it seems pretty popular. https://blog.jaibot.com/the-copenhagen-interpretation-of-ethics/ https://blog.jaibot.com/the-copenhagen-interpretation-of-eth...
- fabian2k 6y ago
  I don't know enough about this trial to decide yet whether it is ethical or not. But there are in any case some differences to a full trial for a vaccine. This is a trial with young people, for a real vaccine trial you also need to know if it works in older people and the mortality is so much higher then that it would be clearly unethical to perform this trial.
  - fallingknife 6y ago
    How can it be unethical if everyone is a volunteer? Also, has there ever been a case of a vaccine that only works on one age group?
    - Closi 6y ago
      I personally find this study totally ethical, but I guess the counter-argument would be “How risky is an experiment allowed to be before it’s considered unethical, even if people are volunteering?”. Like let’s say we wanted to verify if some liquid was a poison, and we thought it had a 50/50 chance of killing someone, and we offer someone £500k to drink it, is that ethical? Probably not. I mean ethics are always subjective, but I don’t think that’s right. Does it make it ethical if it will probably save two lives? Uhh, I’m still uncomfortable with it... So after that point you are just arguing about how risky the experiment is allowed to be before it becomes unethical, and what benefit it will have for other people in relation to that risk. Again, I agree with you and the trial because the risk seems low enough and the reward seems high enough - this is just the counter argument.
  - renewiltord 6y ago
    > or a real vaccine trial you also need to know if it works in older people No, it really doesn't. Most vaccines don't. Maybe one could argue that a COVID-19 vaccine should. But if you had a vaccine that worked on everyone under the age of 60 but worked zero above that, it would still be a 'real' vaccine and we'd be using it everywhere for the cohort it works for. In fact, I can't even imagine what train of thought leads to this statement.
- jedimastert 6y ago
  > dangerous enough to bend the rules of clinical trials to find a vaccine faster Bending ethics regulations because of emergencies is a really dangerous precedent, and a bell I'd rather leave unrung. We don't need to bend the rules when things get bad, we need to have better rules. Subtle but massive difference
- tiahura 6y ago
  To further your point: "Moderna’s mRNA-1273, which reported a 94.5 percent efficacy rate on November 16, had been designed by January 13 [2020]. This was just two days after the genetic sequence had been made public in an act of scientific and humanitarian generosity that resulted in China’s Yong-Zhen Zhang’s being temporarily forced out of his lab. In Massachusetts, the Moderna vaccine design took all of one weekend. It was completed before China had even acknowledged that the disease could be transmitted from human to human, more than a week before the first confirmed coronavirus case in the United States. By the time the first American death was announced a month later, the vaccine had already been manufactured and shipped to the National Institutes of Health for the beginning of its Phase I clinical trial." https://nymag.com/intelligencer/2020/12/moderna-covid-19-vaccine-design.html https://nymag.com/intelligencer/2020/12/moderna-covid-19-vac... It's almost impossible to imagine the devastation that could have been averted if the vaccine was released in March 2020.
  - tialaramex 6y ago
    Or, as several countries did, you could actually pursue elimination and "avert the devastation" without miraculously creating millions of doses of untested vaccine, injecting them into your population and then crossing your fingers that nothing goes wrong.
  - onychomys 6y ago
    That's only because we know in hindsight that it works, though. Phase 1 and 2 trials are important, even though they take time, because there's no guarantee that a vaccine candidate will be safe and effective. See, for example, a couple of Merck candidates that ended up failing [0]. If the Moderna one had been released in March 2020 and injected in millions of people and then they all got sick anyway, it would have been a disaster. [0] https://www.nbcnews.com/health/health-news/merck-discontinues-two-covid-19-vaccine-candidates-n1255503 https://www.nbcnews.com/health/health-news/merck-discontinue...
    - dehrmann 6y ago
      I agree with the importance of safety testing, but I suspect we could have had vaccines 3 months earlier with challenge trials. March was obviously not realistic, and we "had" the vaccine in the same way you have a winning bet in roulette before the wheel stops spinning. Or that Schrodinger still had a living cat.
- renewiltord 6y ago
  I'm going to say what you're carefully tip-toeing around. It isn't strange. It's normal. When you watch people's actions and not their words, you see what they truly believe. The Trolley Problem is most definitely solved in real life. For instance, we can see that we allow rescue divers to die so that trapped children may be saved. The trolley problem has been solved: some number of cave divers' lives are worth less than some larger number of trapped childrens' lives. Should we risk soldiers' lives going to Afghanistan so we can stop Osama Bin Laden and discourage hypothetical future violence against us? Yes, of course. Trolley problem solved. Try it again with COVID-19 and you learn something. The truth is that we don't really care all that much about some elderly dying (rightly so). We care so little about their lives that we wouldn't even risk a thousandth as many people to save them. That's how it goes. Revealed Preferences tell us all we need to know. There is a dollar sum for a life. Some lives are more valuable than other lives. And there is a banal variant of utilitarianism that flows through us all. We are not fools. No species that risks nothing gains anything.
  - s1artibartfast 6y ago
    I think your point is accurate, but more nuanced. you have to include accountability (e.g. blowback against the person who pulls the lever) Inaction is the most attractive option because the decision maker is can avoid blame. We could have taken an aggressive stance against covid, done challenge trials, mobilized manufacturing, used more controversal restrictions on movement. OR We could have taken a more laze fair approach, letting the elderly lock themselves down and die in greater numbers. Instead, we got some middling third option where politicians try to minimize accountability, and we get both very high deaths and very high economic disruption
coding123 6y ago
It's really weird right? On the one hand there's evidence that COVID destroys people's lung function even if you end up being asymptomatic (aka people not noticing they are sick). On the other hand the virus has killed millions so far, and it's going to infect people anyway so why not do it intentionally to better test vaccines or other fixes.
- rkangel 6y ago
  Because it is unethical to intentionally harm someone for the benefit of medical research. I need to read up on it, but I expect that this challenge trial has been given ethical approval because there is now some evidence from the larger (non challenge) trials that a vaccinated person being exposed has a low risk of harm (for the relevant age group).
  - jxcl 6y ago
    Interestingly, they only mention vaccination in the second phase of the trial. It's not clear to me if this is misreported, or they're planning to expose unvaccinated healthy people to small amounts of the virus in phase 1.
    - vilhelm_s 6y ago
      Yes, that's right. > The first stage of this project will explore the feasibility of exposing healthy volunteers to COVID-19. In this initial phase, called the Virus Characterisation Study, the aim will be to discover the smallest amount of virus it takes to cause a person to develop COVID-19. [...] Once the characterisation study is completed, this Human Challenge Study model can be utilised to conduct COVID-19 Human Challenge Studies from mid-2021 subject to regulatory approvals. There are some more detailed writeups at https://www.gov.uk/government/news/worlds-first-coronavirus-human-challenge-study-receives-ethics-approval-in-the-uk https://www.gov.uk/government/news/worlds-first-coronavirus-... and https://hvivo.com/the-human-challenge-programme/ https://hvivo.com/the-human-challenge-programme/
  - oli5679 6y ago
    "Because it is unethical to intentionally harm someone for the benefit of medical research." People incur additional risk for enjoyment, money or to contribute to a social cause in many aspects of life. If you work as a deep-sea-diver, go skydiving, join the army or even frequently drink a lot of alcohol this can increase personal risk significantly. Voluntary challenge trials with well informed, healthy, young participants testing novel vaccines and treatments during pandemics has a very high net utilitarian impact. A < 1/10,000 risk for several hundred 20-30 year old participants is dwarfed by the death and suffering prevented by more quickly having efficacy information. I'm 27, and shy away from many risks, but signed up for '1 day sooner' soon after the pandemic reached the UK, and would be proud to participate in a challenge trial if needed. People framing it as 'unethical' should lay out exactly what their ethical framework is.
tyho 6y ago
I have signed up. Any legal reason to leave the house will do. I am loosing my sanity.
- opwieurposiu 6y ago
  Don't tell the trial about your lack of sanity, insane people can not give informed consent. Seriously though, thanks for taking a risk to help out the human race.
- aphextron 6y ago
  >I am loosing my sanity. Have you ever lost your ability to breathe? I can assure you it's much worse.
  - scrollaway 6y ago
    Have you ever experienced both? I have, and I can unequivocally assure you that you are wrong. Your comment adds nothing to the thread, you're just trying to annoy GP and you're not even correct in your assertions.
    - aphextron 6y ago
      Oh no! I'm forced to sit in my climate controlled, comfortably furnished apartment with my big screen TV, high speed internet access, video games, and food delivery for a few months so that I don't die of a horrible plague or otherwise spread it to my friends and family! I'm losing my sanity! People seriously need to grow up. If there's anything I've learned from this ordeal it's that we are so insanely coddled in western society that literally no one knows what true hardship is in life anymore. We are truly screwed if things actually start hitting the fan at some point.
      - scrollaway 6y ago
        Congrats on your priviledged life. Maybe donate a couple bucks to your local homeless shelter to make up for that awful reply. Three things: 1. Well done you for having "a climate controlled, comfortably furnished apartment, a big screen tv, high speed internet access, video games, and food delivery". If it wasn't obvious, not everybody does. 2. Since, as you're implying, you're not losing your sanity, I'm not sure you have anything to say about the matter. Or to put it another way: You don't get to shit on other people's hardships just because you have it easy in life. 3. "Losing your sanity" can happen outside of lockdown-related ills. You are aware of that, right?
Exmoor 6y ago
This could become increasingly important more of the population becomes vaccinated and case rates continue to fall. If a variant that is able to evade vaccinated immunity occurs we have the technology to quickly develop updated mRNA vaccines to combat it, but with reduced infection rates it could take many months and high number of participants before the efficacy of an updated vaccine or booster is apparent.
philwelch 6y ago
Better late than never, I guess.
handmodel 6y ago
I signed up for human challenge trials last spring so had lots of debates on this - it usually ended with the person saying directly or indirectly "Bioethicists have discussed this for decades and understand it more than you". I found this extremely unconvincing. A group of unelected people, mostly from the same social class, being able to determine the rules of something so important seemed inherently flawed to me. In this particular situation, I saw it as signing up to be a soldier for my country (which always covers some personal risk) - with the number of lives that could have been saved by April 2020 human challenge trial being in the tens or hundreds of thousands of dollars.
- minikites 6y ago
  >A group of unelected people How would it be better if they were elected?
  - TheAdamAndChe 6y ago
    There's at least a possibility of accountability with elected officials. If they work against the peoples' interests too much, they get voted out.
    - gruez 6y ago
      >If they work against the peoples' interests too much, they get voted out. only if the people aren't blinded by partisanship and realize it.
    - minikites 6y ago
      How's that been working out lately?
- dcolkitt 6y ago
  Just because a group focuses on a topic does not mean that they possess any genuine expertise. Nobody rational would claim that we should listen to astrologers about fortune telling. A more prosaic example is that virtually zero mutual fund managers outperform the market. Pundits are not any better at forecasting political events than the average person. Experience alone is not enough. You must demonstrate evidence of actual expertise. Ethicists behave no more ethically than the average person[1], which strongly suggests that the entire field is worthless. A rational person should ignore the established field of bioethics. Maybe even take the opposite of their advice. [1]https://qz.com/1582149/ethicists-are-no-more-ethical-than-the-rest-of-us-study-finds/ https://qz.com/1582149/ethicists-are-no-more-ethical-than-th...
fasteddie31003 6y ago
About 4 months too late. Could have saved lives if we had challenge trials to get more confidence in our vaccines early on. My 2 cents is that society has embraced deontological ethics over consequentialism in this pandemic to its detriment. You can't bake a cake without cracking some eggs.
- da_big_ghey 6y ago
  Interesting take, though I wouldn't call deontological ethics the problem here. Rather, it's that someone choosing to become infected is regarded as "wrong". It's part of a broader trend towards the nanny-state view that people should not be able to do "stupid things" that hurt primarily themselves. Another good example is drug use: marijuana legalization is really driven more by people believing that it is less harmful than by a shift towards letting people do what they want. As long as people give informed consent, choosing to become infected should not be regarded as wrong.
  - waterhouse 6y ago
    Hmm. Although I think the nanny state is real and I hate it as much as anyone, I think this is more about people in FDA-like organizations facing perverse incentives: if they recommend doing a thing and that thing kills people, then they suffer, but if they recommend doing nothing—that is, they use the force of the law to stop people from doing something—and that leads to people dying, then they do not suffer. As a result, they are heavily biased towards obstructionism. There has been some effort to estimate the net impact of the FDA, and, for example, to compare the number of people who have died due to delays of livesaving drugs vs the worst cases of bad drugs getting into the market. https://www.fdareview.org/issues/theory-evidence-and-examples-of-fda-harm/ https://www.fdareview.org/issues/theory-evidence-and-example... cites a bunch of studies—many of whose links have rotted, so you'll want the Internet Archive, e.g.: http://web.archive.org/web/20100603223422/http://www.cato.org/pubs/journal/cj5n1/cj5n1-10.pdf http://web.archive.org/web/20100603223422/http://www.cato.or... . The second link makes a case that the first number is significantly higher. FDA kills. Remember that.
- waterhouse 6y ago
orangecat 6y ago
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.
runako 6y ago
Some people in this thread are saying we should have allowed challenge trials in February 2020, soon after the initial vaccine candidates were developed. But reading TFA: "The drug Remdesivir will be used as soon as volunteers start developing symptoms." Remdesivir broadly wasn't available in February 2020 as an approved drug. It still isn't in the EU, and broad US availability didn't come until the fall. It cannot be overstated how new are many of the drugs involved in the Covid response. It's not just the vaccine platforms, of which at least 2(!) are seeing their first use. Accepted therapeutic options have AFAIK always been a part of challenge trial protocols. The difference is that in e.g. March 2020, the doses given to healthy challenge trial participants would have been quite literally taken from a hospitalized patient on a respirator. That's obviously unethical. (The other option is to ask physicians to violate their Hippocratic oaths during the trial, which is a slippery slope.)
- Closi 6y ago
  I think people are saying that we should have done challenge trials regardless of Remdesivir availability because if for example those trials shortened the pandemic by 1 day for example it would saved tens of thousands of lives. I don't see how taking supply of drugs away from someone in need to support a trial that could save more lives is 'obviously' unethical by the way - ethics aren't obvious and it's not at all clear to me that taking medicine away from a few people in an effort to save many more is inherently unethical. This is effectively the ethical debate between Utilitarianism and Deontology.
  - runako 6y ago
    Agree with your last part, but it's an important tenet of medicine that a patient can trust her doctor. A challenge trial run as you described would either have to be run with no physicians, or with physicians who violate the Hippocratic oath. Either way is going to mar the results.
    - Closi 6y ago
      It don't see how it will make a difference to the quality of the results, as long as good scientific method is followed. With a strict reading of the hippocratic oath, physicians would rarely advise a patient take part in any phase 0/1 medical trial ever (see Theralizumab). In reality, trials need to be carried out to advance medicine and doctors do assist with them alongside researchers. Let's not forget that doctors are present during executions in the USA to give medical support, because the alternative is that people who aren't doctors will have to give medical support. And doctors would never elect to do unnecessary cosmetic surgeries and give ladies very big boobies. I think more benefit comes out of a doctor assisting with a challenge trial than putting even bigger breasts into Cardi B.
Animats 6y ago
Why? This is exposing people to the form of the virus for which vaccines work. What will be learned? If anything, a challenge study for some of the newer variants and vaccines might be worthwhile.
andred14 6y ago
Our governments are the real em3rgency
learnstats2 6y ago
I believe the UK already has one of the highest rates of animal experimentation in the world (if not the actual highest?), i.e. it's known to be relatively easy to get through ethics committees.
ulfw 6y ago
We could have used this a year ago to accelerate vaccine approvals/research. But why now?

114 points by timthorn 6y ago

Strange that, until this point, the virus has been deemed dangerous enough to shut down whole swathes of the economy for a year, but not dangerous enough to bend the rules of clinical trials to find a vaccine faster. If we had done this sooner, we might have got the vaccine out before the mutant strains appeared over the last couple months.

whatshisface 6y ago
The trolley problem solution that gets chosen in real life situations really seems to be a consistent "last person who touched it broke it" policy.
- dehrmann 6y ago
  Politically, it's the winning solution.
- jdminhbg 6y ago
  > The Copenhagen Interpretation of quantum mechanics says that you can have a particle spinning clockwise and counterclockwise at the same time – until you look at it, at which point it definitely becomes one or the other. The theory claims that observing reality fundamentally changes it. > The Copenhagen Interpretation of Ethics says that when you observe or interact with a problem in any way, you can be blamed for it. At the very least, you are to blame for not doing more. Even if you don’t make the problem worse, even if you make it slightly better, the ethical burden of the problem falls on you as soon as you observe it. In particular, if you interact with a problem and benefit from it, you are a complete monster. I don’t subscribe to this school of thought, but it seems pretty popular. https://blog.jaibot.com/the-copenhagen-interpretation-of-ethics/ https://blog.jaibot.com/the-copenhagen-interpretation-of-eth...
fabian2k 6y ago
I don't know enough about this trial to decide yet whether it is ethical or not. But there are in any case some differences to a full trial for a vaccine. This is a trial with young people, for a real vaccine trial you also need to know if it works in older people and the mortality is so much higher then that it would be clearly unethical to perform this trial.
- fallingknife 6y ago
  How can it be unethical if everyone is a volunteer? Also, has there ever been a case of a vaccine that only works on one age group?
  - Closi 6y ago
    I personally find this study totally ethical, but I guess the counter-argument would be “How risky is an experiment allowed to be before it’s considered unethical, even if people are volunteering?”. Like let’s say we wanted to verify if some liquid was a poison, and we thought it had a 50/50 chance of killing someone, and we offer someone £500k to drink it, is that ethical? Probably not. I mean ethics are always subjective, but I don’t think that’s right. Does it make it ethical if it will probably save two lives? Uhh, I’m still uncomfortable with it... So after that point you are just arguing about how risky the experiment is allowed to be before it becomes unethical, and what benefit it will have for other people in relation to that risk. Again, I agree with you and the trial because the risk seems low enough and the reward seems high enough - this is just the counter argument.
- renewiltord 6y ago
  > or a real vaccine trial you also need to know if it works in older people No, it really doesn't. Most vaccines don't. Maybe one could argue that a COVID-19 vaccine should. But if you had a vaccine that worked on everyone under the age of 60 but worked zero above that, it would still be a 'real' vaccine and we'd be using it everywhere for the cohort it works for. In fact, I can't even imagine what train of thought leads to this statement.
jedimastert 6y ago
> dangerous enough to bend the rules of clinical trials to find a vaccine faster Bending ethics regulations because of emergencies is a really dangerous precedent, and a bell I'd rather leave unrung. We don't need to bend the rules when things get bad, we need to have better rules. Subtle but massive difference
tiahura 6y ago
To further your point: "Moderna’s mRNA-1273, which reported a 94.5 percent efficacy rate on November 16, had been designed by January 13 [2020]. This was just two days after the genetic sequence had been made public in an act of scientific and humanitarian generosity that resulted in China’s Yong-Zhen Zhang’s being temporarily forced out of his lab. In Massachusetts, the Moderna vaccine design took all of one weekend. It was completed before China had even acknowledged that the disease could be transmitted from human to human, more than a week before the first confirmed coronavirus case in the United States. By the time the first American death was announced a month later, the vaccine had already been manufactured and shipped to the National Institutes of Health for the beginning of its Phase I clinical trial." https://nymag.com/intelligencer/2020/12/moderna-covid-19-vaccine-design.html https://nymag.com/intelligencer/2020/12/moderna-covid-19-vac... It's almost impossible to imagine the devastation that could have been averted if the vaccine was released in March 2020.
- tialaramex 6y ago
  Or, as several countries did, you could actually pursue elimination and "avert the devastation" without miraculously creating millions of doses of untested vaccine, injecting them into your population and then crossing your fingers that nothing goes wrong.
- onychomys 6y ago
  That's only because we know in hindsight that it works, though. Phase 1 and 2 trials are important, even though they take time, because there's no guarantee that a vaccine candidate will be safe and effective. See, for example, a couple of Merck candidates that ended up failing [0]. If the Moderna one had been released in March 2020 and injected in millions of people and then they all got sick anyway, it would have been a disaster. [0] https://www.nbcnews.com/health/health-news/merck-discontinues-two-covid-19-vaccine-candidates-n1255503 https://www.nbcnews.com/health/health-news/merck-discontinue...
  - dehrmann 6y ago
    I agree with the importance of safety testing, but I suspect we could have had vaccines 3 months earlier with challenge trials. March was obviously not realistic, and we "had" the vaccine in the same way you have a winning bet in roulette before the wheel stops spinning. Or that Schrodinger still had a living cat.
renewiltord 6y ago
I'm going to say what you're carefully tip-toeing around. It isn't strange. It's normal. When you watch people's actions and not their words, you see what they truly believe. The Trolley Problem is most definitely solved in real life. For instance, we can see that we allow rescue divers to die so that trapped children may be saved. The trolley problem has been solved: some number of cave divers' lives are worth less than some larger number of trapped childrens' lives. Should we risk soldiers' lives going to Afghanistan so we can stop Osama Bin Laden and discourage hypothetical future violence against us? Yes, of course. Trolley problem solved. Try it again with COVID-19 and you learn something. The truth is that we don't really care all that much about some elderly dying (rightly so). We care so little about their lives that we wouldn't even risk a thousandth as many people to save them. That's how it goes. Revealed Preferences tell us all we need to know. There is a dollar sum for a life. Some lives are more valuable than other lives. And there is a banal variant of utilitarianism that flows through us all. We are not fools. No species that risks nothing gains anything.
- s1artibartfast 6y ago
  I think your point is accurate, but more nuanced. you have to include accountability (e.g. blowback against the person who pulls the lever) Inaction is the most attractive option because the decision maker is can avoid blame. We could have taken an aggressive stance against covid, done challenge trials, mobilized manufacturing, used more controversal restrictions on movement. OR We could have taken a more laze fair approach, letting the elderly lock themselves down and die in greater numbers. Instead, we got some middling third option where politicians try to minimize accountability, and we get both very high deaths and very high economic disruption

coding123 6y ago

It's really weird right? On the one hand there's evidence that COVID destroys people's lung function even if you end up being asymptomatic (aka people not noticing they are sick). On the other hand the virus has killed millions so far, and it's going to infect people anyway so why not do it intentionally to better test vaccines or other fixes.

rkangel 6y ago
Because it is unethical to intentionally harm someone for the benefit of medical research. I need to read up on it, but I expect that this challenge trial has been given ethical approval because there is now some evidence from the larger (non challenge) trials that a vaccinated person being exposed has a low risk of harm (for the relevant age group).
- jxcl 6y ago
  Interestingly, they only mention vaccination in the second phase of the trial. It's not clear to me if this is misreported, or they're planning to expose unvaccinated healthy people to small amounts of the virus in phase 1.
  - vilhelm_s 6y ago
    Yes, that's right. > The first stage of this project will explore the feasibility of exposing healthy volunteers to COVID-19. In this initial phase, called the Virus Characterisation Study, the aim will be to discover the smallest amount of virus it takes to cause a person to develop COVID-19. [...] Once the characterisation study is completed, this Human Challenge Study model can be utilised to conduct COVID-19 Human Challenge Studies from mid-2021 subject to regulatory approvals. There are some more detailed writeups at https://www.gov.uk/government/news/worlds-first-coronavirus-human-challenge-study-receives-ethics-approval-in-the-uk https://www.gov.uk/government/news/worlds-first-coronavirus-... and https://hvivo.com/the-human-challenge-programme/ https://hvivo.com/the-human-challenge-programme/
- oli5679 6y ago
  "Because it is unethical to intentionally harm someone for the benefit of medical research." People incur additional risk for enjoyment, money or to contribute to a social cause in many aspects of life. If you work as a deep-sea-diver, go skydiving, join the army or even frequently drink a lot of alcohol this can increase personal risk significantly. Voluntary challenge trials with well informed, healthy, young participants testing novel vaccines and treatments during pandemics has a very high net utilitarian impact. A < 1/10,000 risk for several hundred 20-30 year old participants is dwarfed by the death and suffering prevented by more quickly having efficacy information. I'm 27, and shy away from many risks, but signed up for '1 day sooner' soon after the pandemic reached the UK, and would be proud to participate in a challenge trial if needed. People framing it as 'unethical' should lay out exactly what their ethical framework is.

tyho 6y ago

I have signed up. Any legal reason to leave the house will do. I am loosing my sanity.

opwieurposiu 6y ago
Don't tell the trial about your lack of sanity, insane people can not give informed consent. Seriously though, thanks for taking a risk to help out the human race.
aphextron 6y ago
>I am loosing my sanity. Have you ever lost your ability to breathe? I can assure you it's much worse.
- scrollaway 6y ago
  Have you ever experienced both? I have, and I can unequivocally assure you that you are wrong. Your comment adds nothing to the thread, you're just trying to annoy GP and you're not even correct in your assertions.
  - aphextron 6y ago
    Oh no! I'm forced to sit in my climate controlled, comfortably furnished apartment with my big screen TV, high speed internet access, video games, and food delivery for a few months so that I don't die of a horrible plague or otherwise spread it to my friends and family! I'm losing my sanity! People seriously need to grow up. If there's anything I've learned from this ordeal it's that we are so insanely coddled in western society that literally no one knows what true hardship is in life anymore. We are truly screwed if things actually start hitting the fan at some point.
    - scrollaway 6y ago
      Congrats on your priviledged life. Maybe donate a couple bucks to your local homeless shelter to make up for that awful reply. Three things: 1. Well done you for having "a climate controlled, comfortably furnished apartment, a big screen tv, high speed internet access, video games, and food delivery". If it wasn't obvious, not everybody does. 2. Since, as you're implying, you're not losing your sanity, I'm not sure you have anything to say about the matter. Or to put it another way: You don't get to shit on other people's hardships just because you have it easy in life. 3. "Losing your sanity" can happen outside of lockdown-related ills. You are aware of that, right?

Exmoor 6y ago

This could become increasingly important more of the population becomes vaccinated and case rates continue to fall. If a variant that is able to evade vaccinated immunity occurs we have the technology to quickly develop updated mRNA vaccines to combat it, but with reduced infection rates it could take many months and high number of participants before the efficacy of an updated vaccine or booster is apparent.

philwelch 6y ago

Better late than never, I guess.

handmodel 6y ago

I signed up for human challenge trials last spring so had lots of debates on this - it usually ended with the person saying directly or indirectly "Bioethicists have discussed this for decades and understand it more than you". I found this extremely unconvincing. A group of unelected people, mostly from the same social class, being able to determine the rules of something so important seemed inherently flawed to me. In this particular situation, I saw it as signing up to be a soldier for my country (which always covers some personal risk) - with the number of lives that could have been saved by April 2020 human challenge trial being in the tens or hundreds of thousands of dollars.

minikites 6y ago
>A group of unelected people How would it be better if they were elected?
- TheAdamAndChe 6y ago
  There's at least a possibility of accountability with elected officials. If they work against the peoples' interests too much, they get voted out.
  - gruez 6y ago
    >If they work against the peoples' interests too much, they get voted out. only if the people aren't blinded by partisanship and realize it.
  - minikites 6y ago
    How's that been working out lately?
dcolkitt 6y ago
Just because a group focuses on a topic does not mean that they possess any genuine expertise. Nobody rational would claim that we should listen to astrologers about fortune telling. A more prosaic example is that virtually zero mutual fund managers outperform the market. Pundits are not any better at forecasting political events than the average person. Experience alone is not enough. You must demonstrate evidence of actual expertise. Ethicists behave no more ethically than the average person[1], which strongly suggests that the entire field is worthless. A rational person should ignore the established field of bioethics. Maybe even take the opposite of their advice. [1]https://qz.com/1582149/ethicists-are-no-more-ethical-than-the-rest-of-us-study-finds/ https://qz.com/1582149/ethicists-are-no-more-ethical-than-th...

fasteddie31003 6y ago

About 4 months too late. Could have saved lives if we had challenge trials to get more confidence in our vaccines early on. My 2 cents is that society has embraced deontological ethics over consequentialism in this pandemic to its detriment. You can't bake a cake without cracking some eggs.

da_big_ghey 6y ago
Interesting take, though I wouldn't call deontological ethics the problem here. Rather, it's that someone choosing to become infected is regarded as "wrong". It's part of a broader trend towards the nanny-state view that people should not be able to do "stupid things" that hurt primarily themselves. Another good example is drug use: marijuana legalization is really driven more by people believing that it is less harmful than by a shift towards letting people do what they want. As long as people give informed consent, choosing to become infected should not be regarded as wrong.
- waterhouse 6y ago
  Hmm. Although I think the nanny state is real and I hate it as much as anyone, I think this is more about people in FDA-like organizations facing perverse incentives: if they recommend doing a thing and that thing kills people, then they suffer, but if they recommend doing nothing—that is, they use the force of the law to stop people from doing something—and that leads to people dying, then they do not suffer. As a result, they are heavily biased towards obstructionism. There has been some effort to estimate the net impact of the FDA, and, for example, to compare the number of people who have died due to delays of livesaving drugs vs the worst cases of bad drugs getting into the market. https://www.fdareview.org/issues/theory-evidence-and-examples-of-fda-harm/ https://www.fdareview.org/issues/theory-evidence-and-example... cites a bunch of studies—many of whose links have rotted, so you'll want the Internet Archive, e.g.: http://web.archive.org/web/20100603223422/http://www.cato.org/pubs/journal/cj5n1/cj5n1-10.pdf http://web.archive.org/web/20100603223422/http://www.cato.or... . The second link makes a case that the first number is significantly higher. FDA kills. Remember that.
waterhouse 6y ago

orangecat 6y ago

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.

runako 6y ago

Some people in this thread are saying we should have allowed challenge trials in February 2020, soon after the initial vaccine candidates were developed. But reading TFA: "The drug Remdesivir will be used as soon as volunteers start developing symptoms." Remdesivir broadly wasn't available in February 2020 as an approved drug. It still isn't in the EU, and broad US availability didn't come until the fall. It cannot be overstated how new are many of the drugs involved in the Covid response. It's not just the vaccine platforms, of which at least 2(!) are seeing their first use. Accepted therapeutic options have AFAIK always been a part of challenge trial protocols. The difference is that in e.g. March 2020, the doses given to healthy challenge trial participants would have been quite literally taken from a hospitalized patient on a respirator. That's obviously unethical. (The other option is to ask physicians to violate their Hippocratic oaths during the trial, which is a slippery slope.)

Closi 6y ago
I think people are saying that we should have done challenge trials regardless of Remdesivir availability because if for example those trials shortened the pandemic by 1 day for example it would saved tens of thousands of lives. I don't see how taking supply of drugs away from someone in need to support a trial that could save more lives is 'obviously' unethical by the way - ethics aren't obvious and it's not at all clear to me that taking medicine away from a few people in an effort to save many more is inherently unethical. This is effectively the ethical debate between Utilitarianism and Deontology.
- runako 6y ago
  Agree with your last part, but it's an important tenet of medicine that a patient can trust her doctor. A challenge trial run as you described would either have to be run with no physicians, or with physicians who violate the Hippocratic oath. Either way is going to mar the results.
  - Closi 6y ago
    It don't see how it will make a difference to the quality of the results, as long as good scientific method is followed. With a strict reading of the hippocratic oath, physicians would rarely advise a patient take part in any phase 0/1 medical trial ever (see Theralizumab). In reality, trials need to be carried out to advance medicine and doctors do assist with them alongside researchers. Let's not forget that doctors are present during executions in the USA to give medical support, because the alternative is that people who aren't doctors will have to give medical support. And doctors would never elect to do unnecessary cosmetic surgeries and give ladies very big boobies. I think more benefit comes out of a doctor assisting with a challenge trial than putting even bigger breasts into Cardi B.

Animats 6y ago

Why? This is exposing people to the form of the virus for which vaccines work. What will be learned? If anything, a challenge study for some of the newer variants and vaccines might be worthwhile.

andred14 6y ago

Our governments are the real em3rgency

learnstats2 6y ago

I believe the UK already has one of the highest rates of animal experimentation in the world (if not the actual highest?), i.e. it's known to be relatively easy to get through ethics committees.

ulfw 6y ago

We could have used this a year ago to accelerate vaccine approvals/research. But why now?