Let me suggest that human challenge trials are a bad idea in a pandemic such as this, because they’re too slow.
We can see, from RADVAC use that competent experts who were focused on minimizing their personal risk, that at least some untested vaccines look safer than a lack of vaccines.
So the only ethical strategy was to approve emergency use of at least some vaccines back around February. Possibly there were some vaccines were too novel for this to be safe. Do any of the people who are saying untested vaccines are risky quantify the risks that they believe support their position?
Why might the experts with the most media attention be wrong about this?
the FDA is scared of anything which would suggest that their normal process hurts people by delaying good medicine.
pharma companies are worried that competitors will be able to sell new medicines more easily.
both expect to be blamed much more for harm caused by medicine than for harm due to lack of medicine.
Hi Peter! That line of argument should be an important part of this discussion as well.
For an individual person, it’s unquestionably better to give them an untested vaccine and no disease (as in administering an untested vaccine in the context of a conventional trial), rather than an untested vaccine and a disease (as in a human challenge trial). The tradeoffs between conventional trials, HCTs, and untested emergency voluntary mass vaccination campaigns, are less clear at a population level, which is why I think it needs more study and debate.
I focused this post around HCTs because they seem more conventional than emergency untested vaccination campaigns. It seemed to me that anyone hesitant about changing the status quo would be more likely to support HCTs than a mass untested vaccination campaign.
Now, I’m not so sure. The ethical qualm with HCTs is rooted in a medical ethic that prioritizes the wellbeing of the individual.
Imagine we face a another pandemic. We knowthe disease is deadly and that we have no treatment for it. We have reason to think the vaccine is relatively safe and at least somewhat helpful. Under those conditions, it seems like the best way to prioritize the wellbeing of individual patients is to allow them to take an untested vaccine.
So the key unquestioned assumption is not the ethics of HCTs. That at least has been examined, if insufficiently. It’s not even the ethics of administering an under- or untested medical treatment, which we already do all the time.
Instead, it’s the ethics of requiring that phase III trials have the minimum power/study size to gather adequate safety and efficacy data.
Why can’t we instead say that in emergency circumstances, it’s unethical to limit the study size? Instead, when a disease becomes a deadly pandemic to the extent that we’re considering lockdowns, the entire population should have the opportunity to voluntarily participate in a vaccine trial. We already allow Phase I and Phase II to be combined. Why not also allow Phase III to be expanded?
I’m going to start exploring that angle; I wonder if that will be a more tractable approach to rethinking our pandemic response.
So I think that you’re right to point out the bias that many experts have in overprioritizing wanting to avoid harm from a vaccine at the cost of ongoing deaths from the pandemic. That’s likely a very strong consideration playing into their judgments here, and one that should be fought against.
That being said, I think another concern that is underappreciated in these debates is lack of efficacy, rather than lack of safety. What if—and this is probably more likely—a vaccine doesn’t result in any harm, but also just doesn’t do anything to prevent disease? How much time have you spent getting pharma to invest time and resources into developing a manufacturing process for a particular vaccine, and getting the vaccine distributed to people, only to find out it doesn’t work? How many people will have lost trust in the vaccine development process such that they won’t take a subsequent vaccine, even if it works much better? Do you really have the option to “start over”? Maybe moreso now than ever the answer is “yes” given the relative agility with which you can move from design to manufacturing process with mRNA vaccines, but with anything cell culture-based you’ve probably lost months, at which point you might be in a worse situation than if you’d started with trials. This scenario doesn’t have to play out with literally zero efficacy, the same considerations apply if you have, say, 30% efficacy. You could blow your shot at developing a 90% efficacy vaccine b/c you’ve spent down all your resources on the 30% efficacy one.
The implicit theory behind this concern is that you have a limited bank of public trust + resources to work with, such that if you spend it all on the first try and it doesn’t work out, then there’s no going back. So best to make sure your one try definitely goes well, e.g. by setting up trials first.
I think it’s unclear exactly to what extent this theory holds up, but I think it warrants serious consideration. Too often I think these debates stop at “well the expected risk of harm to any given individual from even an untested vaccine is much less than the expected risk of harm from being unvaccinated, so we should give untested vaccines as early as possible” rather than considering the true counterfactual at a society-wide level.
Potential counterargument against the above: Well, yes, any individual pharma company might only have one shot, but as a society we could have many different untested vaccine candidates going out to people all at once. We already have a risk diversification mechanism by having many different vaccine candidate options, so we don’t need to further avoid risk by doing trials on all of them. And we also don’t have to give untested vaccines to literally everybody, just small populations at first.
Response to the counterargument: If the proposal is to give a bunch of untested vaccine candidates to people early on in the pandemic before knowing for sure how they work, haven’t you just reinvented clinical trials? Maybe a conception of them that is faster and to a larger population, but still fundamentally the same thing?
Let me suggest that human challenge trials are a bad idea in a pandemic such as this, because they’re too slow.
We can see, from RADVAC use that competent experts who were focused on minimizing their personal risk, that at least some untested vaccines look safer than a lack of vaccines.
So the only ethical strategy was to approve emergency use of at least some vaccines back around February. Possibly there were some vaccines were too novel for this to be safe. Do any of the people who are saying untested vaccines are risky quantify the risks that they believe support their position?
Why might the experts with the most media attention be wrong about this?
the FDA is scared of anything which would suggest that their normal process hurts people by delaying good medicine.
pharma companies are worried that competitors will be able to sell new medicines more easily.
both expect to be blamed much more for harm caused by medicine than for harm due to lack of medicine.
Hi Peter! That line of argument should be an important part of this discussion as well.
For an individual person, it’s unquestionably better to give them an untested vaccine and no disease (as in administering an untested vaccine in the context of a conventional trial), rather than an untested vaccine and a disease (as in a human challenge trial). The tradeoffs between conventional trials, HCTs, and untested emergency voluntary mass vaccination campaigns, are less clear at a population level, which is why I think it needs more study and debate.
I focused this post around HCTs because they seem more conventional than emergency untested vaccination campaigns. It seemed to me that anyone hesitant about changing the status quo would be more likely to support HCTs than a mass untested vaccination campaign.
Now, I’m not so sure. The ethical qualm with HCTs is rooted in a medical ethic that prioritizes the wellbeing of the individual.
Imagine we face a another pandemic. We know the disease is deadly and that we have no treatment for it. We have reason to think the vaccine is relatively safe and at least somewhat helpful. Under those conditions, it seems like the best way to prioritize the wellbeing of individual patients is to allow them to take an untested vaccine.
So the key unquestioned assumption is not the ethics of HCTs. That at least has been examined, if insufficiently. It’s not even the ethics of administering an under- or untested medical treatment, which we already do all the time.
Instead, it’s the ethics of requiring that phase III trials have the minimum power/study size to gather adequate safety and efficacy data.
Why can’t we instead say that in emergency circumstances, it’s unethical to limit the study size? Instead, when a disease becomes a deadly pandemic to the extent that we’re considering lockdowns, the entire population should have the opportunity to voluntarily participate in a vaccine trial. We already allow Phase I and Phase II to be combined. Why not also allow Phase III to be expanded?
I’m going to start exploring that angle; I wonder if that will be a more tractable approach to rethinking our pandemic response.
So I think that you’re right to point out the bias that many experts have in overprioritizing wanting to avoid harm from a vaccine at the cost of ongoing deaths from the pandemic. That’s likely a very strong consideration playing into their judgments here, and one that should be fought against.
That being said, I think another concern that is underappreciated in these debates is lack of efficacy, rather than lack of safety. What if—and this is probably more likely—a vaccine doesn’t result in any harm, but also just doesn’t do anything to prevent disease? How much time have you spent getting pharma to invest time and resources into developing a manufacturing process for a particular vaccine, and getting the vaccine distributed to people, only to find out it doesn’t work? How many people will have lost trust in the vaccine development process such that they won’t take a subsequent vaccine, even if it works much better? Do you really have the option to “start over”? Maybe moreso now than ever the answer is “yes” given the relative agility with which you can move from design to manufacturing process with mRNA vaccines, but with anything cell culture-based you’ve probably lost months, at which point you might be in a worse situation than if you’d started with trials. This scenario doesn’t have to play out with literally zero efficacy, the same considerations apply if you have, say, 30% efficacy. You could blow your shot at developing a 90% efficacy vaccine b/c you’ve spent down all your resources on the 30% efficacy one.
The implicit theory behind this concern is that you have a limited bank of public trust + resources to work with, such that if you spend it all on the first try and it doesn’t work out, then there’s no going back. So best to make sure your one try definitely goes well, e.g. by setting up trials first.
I think it’s unclear exactly to what extent this theory holds up, but I think it warrants serious consideration. Too often I think these debates stop at “well the expected risk of harm to any given individual from even an untested vaccine is much less than the expected risk of harm from being unvaccinated, so we should give untested vaccines as early as possible” rather than considering the true counterfactual at a society-wide level.
Potential counterargument against the above: Well, yes, any individual pharma company might only have one shot, but as a society we could have many different untested vaccine candidates going out to people all at once. We already have a risk diversification mechanism by having many different vaccine candidate options, so we don’t need to further avoid risk by doing trials on all of them. And we also don’t have to give untested vaccines to literally everybody, just small populations at first.
Response to the counterargument: If the proposal is to give a bunch of untested vaccine candidates to people early on in the pandemic before knowing for sure how they work, haven’t you just reinvented clinical trials? Maybe a conception of them that is faster and to a larger population, but still fundamentally the same thing?