In this post and the last one, you’ve indicated that you don’t see a point to pausing a vaccine’s trial in the face of an adverse event, and that normal processes should be overridden.
I think this may be a case where contemplating Chesterton’s Fence is appropriate.
I’ve seen several people who I would trust to understand this stuff well lay out justifications for due caution in the vaccine development process.
Here’s one set of reasons from a biostatistician (Natalie Dean):
“Widespread use of an unproven vaccine:
Gives people a false sense of security if efficacy is really low
Diverts resources away from other interventions (fixing testing!)
″...the political situation has raised a real possibility that the President of the USA would try to make the FDA authorise a vaccine without convincing evidence that it works. I don’t use words like ‘disaster’ lightly, but this would be a disaster, both for COVID prevention and for the long-term credibility of vaccination. We need a vaccine that works, and we need people to know that it works.”
Lumley again, specifically on the issue of a pause:
“Vaccines aren’t intrinsically safe; they are safe when approved because they get thoroughly investigated first.
The immediate question for the trial sponsor and investigators in this case is whether the adverse event, whatever it is, significantly changes the risk:benefit balance of the vaccine candidate, as explained to the study participants (and to the company’s investors). So far, no-one knows, but AstraZeneca seem to be handling this appropriately, and there’s no obvious reason to expect that to change.”
I have no reason to doubt that these experts share all our desires for this disease to be dealt with as quickly as possible. They’re saying that we should still take appropriate care in developing and testing vaccines. There is at least a risk that reducing normal precautions could increase the duration of the disease causing problems, if we’re left with a less effective vaccine, or if the first vaccine is not safe enough so people lose trust, not just in that one but in all subsequent vaccines.
And although the paused trial has been resumed, that doesn’t provide evidence that it “never had a good reason to pause”. In fact, possibly the reverse. The prompt resumption shows that the processes that the investigators wanted to go through were possible to be conducted quickly, lessening their costliness (in terms of time to successful vaccine).
In the case of the pause, I wasn’t saying that it was time, that day, to give the vaccine to the public. I was saying that they should continue the trial while they investigate the one case, until such time as they actually find a problem linked to the vaccine, so as to not lose time. The downside risk there seems to be almost zero.
The quotes above are all just further “ethicists” who make their prestige and money from expressing concerns and stopping people from doing things, expressing concern and stopping people from doing things, and forcing their procedures on people regardless of whether they make sense. Nothing there is new to me.
As Dagon says, if you think we should use the same speed and standards now that we would use in a non-crisis that wasn’t causing massive damage to lives and livelihoods and the entire world, then I don’t think that’s how trade-offs work and am confused.
I won’t get further into the specifics, but I find the arguments raised here both things I’ve dealt with before, and highly uncompelling.
In the case of the pause, I wasn’t saying that it was time, that day, to give the vaccine to the public. I was saying that they should continue the trial while they investigate the one case, until such time as they actually find a problem linked to the vaccine, so as to not lose time. The downside risk there seems to be almost zero.
A direct downside risk of not pausing a trial when you identify an adverse event that shows your vaccine might have harmed one of your volunteers is that you might harm more of your volunteers.
A knock-on downside risk from that is that fewer people might feel confident volunteering if you’re not taking reasonable precautions with their safety, so you might find it harder, or at least slower, to complete your trial.
I would also suspect that there would be contagion of this distrust, making it harder to run trials of any vaccines, both for COVID and into the future.
...”ethicists” who make their prestige and money from expressing concerns and stopping people from doing things...
Might be worth noting that probably no one is strictly stopping you from taking a vaccine of unknown effectiveness and safety. They are just reducing your probability of doing it down to 0.5. If you feel that the tradeoffs favour taking it, then you can volunteer to be in a trial. The world needs people who are willing to put themselves in that position.
To clarify, are you adopting an ethical position where it is wrong for one person to put themselves at risk to benefit others?
Or are you asserting that there is more suffering and death in the world where the trial continues than in the world where it stops?
Do you perhaps believe that causing suffering by inaction is less morally wrong than causing suffering by action?
Looking for crux.
are you adopting an ethical position where it is wrong for one person to put themselves at risk to benefit others?
No. Volunteers in a clinical trial like this are putting themselves at risk to benefit others, and I feel that is a good thing.
I am concerned about people’s ability to give informed consent. It seems like a hard problem in general to give prospective volunteers a sense of how much risk they are being exposed to—one issue being that people might tend to assume ‘well, whatever they’re saying about risks, it must be pretty safe it they wouldn’t be doing it’. I feel that the ethical thing is to be as good at ensuring consent is informed as is practicable.
I tend to feel that if you continued to admit volunteers to a trial when a potential serious event had occurred, this issue of consent might get trickier. If you don’t tell the next volunteers at all, then it feels like you’re withholding information, meaning their consent is inadequately informed, so I’d be pretty concerned about that. If you do tell them, but continue admitting them, the message of ‘yeah, something bad maybe happened and we want you to know about it before you agree’ might be read by volunteers as having an implicit content of ‘but it’s not that bad or we wouldn’t still be injecting you’.
Of course you might end up with the information putting lots of prospective volunteers off. In that case, you might lose people who would have been volunteers after a pause.
Or are you asserting that there is more suffering and death in the world where the trial continues than in the world where it stops?
I think this is closer to my sense. My guess is that in expectation, a world in which we take pauses (as short as possible) to investigate potential problems with emerging vaccines for a disease like COVID 19, is likely to have less suffering in the long run. Vaccines are not inherently safe, nor are they necessarily trusted by the public even if they are safe. Actions that might let an unsafe vaccine slip through the net have the potential to cause vast harms in terms of the reduced uptake of lots of other vaccines. Even the perception that a vaccine was rushed without taking appropriate safety precautions can result in it getting blamed for things that it doesn’t cause (see the story of the 1976 swine flu vaccine https://www.bbc.com/future/article/20200918-the-fiasco-of-the-us-swine-flu-affair-of-1976 ). Actions that show that care was taken to vet and understand any potential harms will help to improve uptake across all the range of vaccines.
I’m not a philosopher so I won’t say much about your earlier point. It’s worth noting that lots of painful but clearly worthwhile events in history are not worthwhile in your ethical system.
For example, the soldiers at D-Day had much greater uncertainty about their odds of survival than the vaccine trial victims (some beaches were much more dangerous than others). If it’s unethical to allow a volunteer to hurt themselves unless they have total certainty of the risks, the Normandy landings were totally unethical regardless of the suffering in occupied Europe. You can take that ethical system if you want, but it is very distant from conventional ethics.
Excess us deaths are about 10,000 per week. So a one week delay in a vaccine would cost 10,000 deaths. You say a loss of trust in vaccines is possible if the trial is not stopped is possible. But it is also true that if Russia and China start mass Good-enough vaccine distribution long before the US people may lose trust. Can you make an argument that if trials are not suspended a loss of trust in vaccines is more likely than if they are continued? Otherwise the argument isn’t very compelling, no?
My understanding is that there was conscription during WW2, so the comparison is somewhat weakened if we’re not talking about volunteers anyway. But in an armed conflict, I think people have a fair sense that the flying bullets makes it “really rather dangerous”, even if they couldn’t quantify it. My problem with how informed consent can be is around issues like we know there are biases where people have a tendency toward a dichotomy: low risk becomes zero risk in their minds. (To the extent that this applies at the other end of the spectrum, high risk would become near certainty, so further makes the war situation different in nature.)
Can you make an argument that if trials are not suspended a loss of trust in vaccines is more likely than if they are continued?
This seems self evidently true to me. I struggle to envisage a situation where people see caution that they perceive to be excessive and become more reluctant to take vaccines in the future.
Good to have a number for some comparisons. From a quick search, I see the WHO estimates that measles deaths globally fell from 535,600 in 2000 to 124,000 in 2017, but rose to 142,300 in 2018. That seems to show that vaccine uptake can make differences in the tens to hundreds of thousands. Yes, I’m comparing globally to one country, but on the flipside, I’d envisage that negative harms from increased skepticism could aggregate over years-to-decades, and over numerous diseases.
My problem with how informed consent can be is around issues like we know there are biases where people have a tendency toward a dichotomy: low risk becomes zero risk in their minds.
If the changes in risk are very small, in this case of order one in ten thousand, the ethical consequences of people miscalculating that risk are small. We already know that millions of people were willing to take huge risks (<1/100) for altruistic reasons. Why would we assume these volunteers would desist if they “rationally” evaluated the risk at one in ten thousand instead of approximating it at 1 in a hundred thousand?
So for the set of actions that put others in harms way, you believe that the ethics of said action depends on the percent difference between their perceived risk and the actual risk? That is really really weird and far from the point. Say I volunteer for activity A on the assumption that the risk is 1 in a million, but the actual risk is 10 in a million. Then I volunteer for activity B on the assumtion that the risk is 1 in a hundred, but the actual risk is 1 in ten. In both cases the proportion of risk change is a factor of 10, so you would argue they are equally unethical But the change in absolute risk change in activity B was 9%, which is a huge chance of dying! If I am volunteering I am very interested in the absolute change in risk, who cares about the percentage change, because I’m worried about dying not being wrong.
We don’t have to baby people just because they use heuristics to do good.
This seems self evidently true to me. I struggle to envisage a situation where people see caution that they perceive to be excessive and become more reluctant to take vaccines in the future.
People don’t spend that much time thinking about your particular institution’s paricular norms when they assign a trust value (because there are lots of institutions so they don’t have unlimited time). This is the reason courts are built like they are, so people can actually watch the judge deliberate and explain his reasoning. People do not trust courts because juries are statistically good at identifying guilt or because they know the regulations in their jurisdiction in detail. They judge the courts on big noticable surface characteristics that touch their lives and their communities.
They will remember stuff like “did the vaccine work” “did we get it first” and maybe “did people have negative reactions on facebook”. The choices made in one particular trial will be long long forgotten. The UK’s choice to continue the trial gets them more data faster to release a safe vaccine to the genpop. Those are things that touch people. So the UK might experience higher “trust in vaccine institutions” later than the US. It could go the otherway too, but I think the UK choice is stronger in expectation.
Also, the generation who stopped taking measles had forgotten how bad viruses are. I doubt they’ll repeat that mistake after this.
If you think the identical processes and level of caution should be used for an emergent pandemic as for relatively small-scale long-standing viruses, you’re not doing cost/benefit analysis very well. It’s very hard for me to simultaneously believe that it’s so risky that we should all avoid travel and most leisure activities, AND that the vaccine is so unimportant that we shouldn’t accept more risks than we otherwise would.
I’ll respond to Natalie Dean’s quote, because they’re easy bullet points.
Gives people a false sense of security if efficacy is really low
Perhaps true, but efficacy would have to be ridiculously low for it to be a net loss. Which will show in early trials and uses.
Diverts resources away from other interventions (fixing testing!)
Do both!
Makes it harder to evaluate better vaccines
Only to the extent that it’s effective and very common. Which is a good outcome in itself.
See also this marginal revolution comments section, where several comments do show their work. Different conclusions, but this way of arguing for is more effective for finding the option that saves most lives in expectation.
In this post and the last one, you’ve indicated that you don’t see a point to pausing a vaccine’s trial in the face of an adverse event, and that normal processes should be overridden.
I think this may be a case where contemplating Chesterton’s Fence is appropriate.
I’ve seen several people who I would trust to understand this stuff well lay out justifications for due caution in the vaccine development process.
Here’s one set of reasons from a biostatistician (Natalie Dean):
“Widespread use of an unproven vaccine:
Gives people a false sense of security if efficacy is really low
Diverts resources away from other interventions (fixing testing!)
Makes it harder to evaluate better vaccines
Jeopardizes safety
Erodes trust in the process”
https://mobile.twitter.com/nataliexdean/status/1289927701273378816
And another biostatistician (Thomas Lumley):
https://www.statschat.org.nz/2020/09/14/not-quite-alarmed/
Lumley again, specifically on the issue of a pause:
https://www.statschat.org.nz/2020/09/09/adverse-events-some-terminology/
I have no reason to doubt that these experts share all our desires for this disease to be dealt with as quickly as possible. They’re saying that we should still take appropriate care in developing and testing vaccines. There is at least a risk that reducing normal precautions could increase the duration of the disease causing problems, if we’re left with a less effective vaccine, or if the first vaccine is not safe enough so people lose trust, not just in that one but in all subsequent vaccines.
And although the paused trial has been resumed, that doesn’t provide evidence that it “never had a good reason to pause”. In fact, possibly the reverse. The prompt resumption shows that the processes that the investigators wanted to go through were possible to be conducted quickly, lessening their costliness (in terms of time to successful vaccine).
In the case of the pause, I wasn’t saying that it was time, that day, to give the vaccine to the public. I was saying that they should continue the trial while they investigate the one case, until such time as they actually find a problem linked to the vaccine, so as to not lose time. The downside risk there seems to be almost zero.
The quotes above are all just further “ethicists” who make their prestige and money from expressing concerns and stopping people from doing things, expressing concern and stopping people from doing things, and forcing their procedures on people regardless of whether they make sense. Nothing there is new to me.
As Dagon says, if you think we should use the same speed and standards now that we would use in a non-crisis that wasn’t causing massive damage to lives and livelihoods and the entire world, then I don’t think that’s how trade-offs work and am confused.
I won’t get further into the specifics, but I find the arguments raised here both things I’ve dealt with before, and highly uncompelling.
A direct downside risk of not pausing a trial when you identify an adverse event that shows your vaccine might have harmed one of your volunteers is that you might harm more of your volunteers.
A knock-on downside risk from that is that fewer people might feel confident volunteering if you’re not taking reasonable precautions with their safety, so you might find it harder, or at least slower, to complete your trial.
I would also suspect that there would be contagion of this distrust, making it harder to run trials of any vaccines, both for COVID and into the future.
Might be worth noting that probably no one is strictly stopping you from taking a vaccine of unknown effectiveness and safety. They are just reducing your probability of doing it down to 0.5. If you feel that the tradeoffs favour taking it, then you can volunteer to be in a trial. The world needs people who are willing to put themselves in that position.
To clarify, are you adopting an ethical position where it is wrong for one person to put themselves at risk to benefit others? Or are you asserting that there is more suffering and death in the world where the trial continues than in the world where it stops? Do you perhaps believe that causing suffering by inaction is less morally wrong than causing suffering by action? Looking for crux.
No. Volunteers in a clinical trial like this are putting themselves at risk to benefit others, and I feel that is a good thing.
I am concerned about people’s ability to give informed consent. It seems like a hard problem in general to give prospective volunteers a sense of how much risk they are being exposed to—one issue being that people might tend to assume ‘well, whatever they’re saying about risks, it must be pretty safe it they wouldn’t be doing it’. I feel that the ethical thing is to be as good at ensuring consent is informed as is practicable.
I tend to feel that if you continued to admit volunteers to a trial when a potential serious event had occurred, this issue of consent might get trickier. If you don’t tell the next volunteers at all, then it feels like you’re withholding information, meaning their consent is inadequately informed, so I’d be pretty concerned about that. If you do tell them, but continue admitting them, the message of ‘yeah, something bad maybe happened and we want you to know about it before you agree’ might be read by volunteers as having an implicit content of ‘but it’s not that bad or we wouldn’t still be injecting you’.
Of course you might end up with the information putting lots of prospective volunteers off. In that case, you might lose people who would have been volunteers after a pause.
I think this is closer to my sense. My guess is that in expectation, a world in which we take pauses (as short as possible) to investigate potential problems with emerging vaccines for a disease like COVID 19, is likely to have less suffering in the long run. Vaccines are not inherently safe, nor are they necessarily trusted by the public even if they are safe. Actions that might let an unsafe vaccine slip through the net have the potential to cause vast harms in terms of the reduced uptake of lots of other vaccines. Even the perception that a vaccine was rushed without taking appropriate safety precautions can result in it getting blamed for things that it doesn’t cause (see the story of the 1976 swine flu vaccine https://www.bbc.com/future/article/20200918-the-fiasco-of-the-us-swine-flu-affair-of-1976 ). Actions that show that care was taken to vet and understand any potential harms will help to improve uptake across all the range of vaccines.
I’m not a philosopher so I won’t say much about your earlier point. It’s worth noting that lots of painful but clearly worthwhile events in history are not worthwhile in your ethical system. For example, the soldiers at D-Day had much greater uncertainty about their odds of survival than the vaccine trial victims (some beaches were much more dangerous than others). If it’s unethical to allow a volunteer to hurt themselves unless they have total certainty of the risks, the Normandy landings were totally unethical regardless of the suffering in occupied Europe. You can take that ethical system if you want, but it is very distant from conventional ethics.
Excess us deaths are about 10,000 per week. So a one week delay in a vaccine would cost 10,000 deaths. You say a loss of trust in vaccines is possible if the trial is not stopped is possible. But it is also true that if Russia and China start mass Good-enough vaccine distribution long before the US people may lose trust. Can you make an argument that if trials are not suspended a loss of trust in vaccines is more likely than if they are continued? Otherwise the argument isn’t very compelling, no?
My understanding is that there was conscription during WW2, so the comparison is somewhat weakened if we’re not talking about volunteers anyway. But in an armed conflict, I think people have a fair sense that the flying bullets makes it “really rather dangerous”, even if they couldn’t quantify it. My problem with how informed consent can be is around issues like we know there are biases where people have a tendency toward a dichotomy: low risk becomes zero risk in their minds. (To the extent that this applies at the other end of the spectrum, high risk would become near certainty, so further makes the war situation different in nature.)
This seems self evidently true to me. I struggle to envisage a situation where people see caution that they perceive to be excessive and become more reluctant to take vaccines in the future.
Good to have a number for some comparisons. From a quick search, I see the WHO estimates that measles deaths globally fell from 535,600 in 2000 to 124,000 in 2017, but rose to 142,300 in 2018. That seems to show that vaccine uptake can make differences in the tens to hundreds of thousands. Yes, I’m comparing globally to one country, but on the flipside, I’d envisage that negative harms from increased skepticism could aggregate over years-to-decades, and over numerous diseases.
https://www.who.int/news-room/detail/05-12-2019-more-than-140-000-die-from-measles-as-cases-surge-worldwide
If the changes in risk are very small, in this case of order one in ten thousand, the ethical consequences of people miscalculating that risk are small. We already know that millions of people were willing to take huge risks (<1/100) for altruistic reasons. Why would we assume these volunteers would desist if they “rationally” evaluated the risk at one in ten thousand instead of approximating it at 1 in a hundred thousand?
So for the set of actions that put others in harms way, you believe that the ethics of said action depends on the percent difference between their perceived risk and the actual risk? That is really really weird and far from the point. Say I volunteer for activity A on the assumption that the risk is 1 in a million, but the actual risk is 10 in a million. Then I volunteer for activity B on the assumtion that the risk is 1 in a hundred, but the actual risk is 1 in ten. In both cases the proportion of risk change is a factor of 10, so you would argue they are equally unethical But the change in absolute risk change in activity B was 9%, which is a huge chance of dying! If I am volunteering I am very interested in the absolute change in risk, who cares about the percentage change, because I’m worried about dying not being wrong.
We don’t have to baby people just because they use heuristics to do good.
People don’t spend that much time thinking about your particular institution’s paricular norms when they assign a trust value (because there are lots of institutions so they don’t have unlimited time). This is the reason courts are built like they are, so people can actually watch the judge deliberate and explain his reasoning. People do not trust courts because juries are statistically good at identifying guilt or because they know the regulations in their jurisdiction in detail. They judge the courts on big noticable surface characteristics that touch their lives and their communities.
They will remember stuff like “did the vaccine work” “did we get it first” and maybe “did people have negative reactions on facebook”. The choices made in one particular trial will be long long forgotten. The UK’s choice to continue the trial gets them more data faster to release a safe vaccine to the genpop. Those are things that touch people. So the UK might experience higher “trust in vaccine institutions” later than the US. It could go the otherway too, but I think the UK choice is stronger in expectation.
Also, the generation who stopped taking measles had forgotten how bad viruses are. I doubt they’ll repeat that mistake after this.
If you think the identical processes and level of caution should be used for an emergent pandemic as for relatively small-scale long-standing viruses, you’re not doing cost/benefit analysis very well. It’s very hard for me to simultaneously believe that it’s so risky that we should all avoid travel and most leisure activities, AND that the vaccine is so unimportant that we shouldn’t accept more risks than we otherwise would.
I’ll respond to Natalie Dean’s quote, because they’re easy bullet points.
Perhaps true, but efficacy would have to be ridiculously low for it to be a net loss. Which will show in early trials and uses.
Do both!
Only to the extent that it’s effective and very common. Which is a good outcome in itself.
More than a 6-month delay would? I doubt it.
That implies that anyone trusts the process now.
Good points Dagon.
See also this marginal revolution comments section, where several comments do show their work. Different conclusions, but this way of arguing for is more effective for finding the option that saves most lives in expectation.
https://marginalrevolution.com/marginalrevolution/2020/09/on-vaccine-timing-from-the-comments.html