I can actually expand on this a little bit for you.
HCTs have been run in the past, but only for diseases where we had an efficacious treatment. The reason COVID HCTs would only have been run in the Phase 3 stage is because early in the pandemic, we had no proven-effective treatment.
This is a choice based on ethical and political reasoning, rather than science.
As Peter McCluskey points out, the choice not to begin an immediate mass-vaccination campaign with the untested mRNA vaccines we had on January 13th is likewise based on political and ethical reasoning, rather than a scientific choice. We now know, of course, that those vaccines were extremely effective. We’d have saved a colossal number of lives if we had. If we’d paused to run HCTs early on and then distributed the vaccines, we’d have still saved the vast bulk of lives that have been lost.
It’s only because our institutional leaders have made the ethical and political choices they have on our behalf that HCTs appear to be ineffective. We could have made different choices that were equally scientific, but based on different political and ethical reasoning. Continuing with our conventional ethical/political choice cost us over a million lives. Is it worth it? Medical ethicists disagree, none of the experts are talking about it enough, and it’s time for them to step it up and for The People to have a say.
OK, let’s talk about some of the issues that would arise in this scenario.
Taking an mRNA vaccine means becoming temporarily transgenic. mRNA for Covid spike protein is injected into your muscle cells, they produce it, and this stimulates antibody production.
In having trials, one is not only testing that the Covid mRNA vaccine is effective against Covid; one is also testing whether the vaccine itself has side effects.
Are you proposing to move straight to mass vaccination, without testing for vaccine side effects? But if not, how will making the trials HCTs, save time? HCTs are only different in the way that they test efficacy against the pathogen. When it comes to testing for side effects of the vaccine itself, don’t you have to wait just as long as you do, in a non-challenge trial?
Vaccinate with safety and efficacy data (conventional trials)
Vaccinate only with efficacy data (early HCTs)
Vaccinate with no data (immediate vaccination campaign on development of a vaccine)
I’m advocating that option 2 and option 3 be considered as realistic scientific, ethical, and political possibilities during the early stage of a deadly future pandemic akin to the one we face now.
Two of the questions I still have are:
What are the worst side effects of any vaccine that’s ever been tested?
How frequently do vaccines fail in conventional trials due to safety concerns?
This paper finds that 33% of tested vaccines have made it through all 3 trial phases. One of the worst consequences of a historically approved vaccine, used as an example by the AAMC of why we can’t rush a COVID-19 vaccine, was the polio vaccine where 120,000 doses contained live virus.
This caused ten deaths. Stack that up against over 1.6 million and counting.
Once again, I’m not strictly saying the AAMC is wrong. But they are begging the question. Comparing the historical base rate of deaths due to unsafe vaccines vs. the base rate of expected deaths due to COVID-19 is, on its face, a pretty reasonable and obvious approach to evaluating what we should do.
The AAMC glosses right over this issue. They must know it’s why many of their readers are looking up the article in the first place. So they’re choosing to ignore this line of thinking. I’m asking them to stop ignoring it.
If (2) and (3) were seriously considered, then I’d think you’d particularly want to avoid using only a single vaccine.
From a civilizational point of view, the largest issue isn’t the expectation of the direct outcome—it’s that there’s a small chance you may have a bad outcome with very little variance across the population.
I’d be much less concerned about doing (2) or (3) with twenty different vaccines than with one.
Black Swan considerations definitely apply here. Although as far as I know, we haven’t had a vaccine that outright killed the majority of the people taking it, it’s not impossible. Maybe it’s just rare enough that we haven’t established a meaningful base rate. You’d also want to be concerned about the possibility of interactions from giving multiple vaccines to one person.
It might make sense to do something like vaccinating populations in the hardest-hit areas first, trying new vaccines as they become available, prioritizing the safest and most effective vaccines as data emerges.
If you want to make the case that with a different ethos, Covid-19 mortality might have been dramatically lower, it would help to exhibit a scenario in which this happens.
Much is being made of the fact that mRNA vaccines were first synthesized, very soon after the virus’s genetic sequence became available. But this just means that a particular molecular construct (a carrier for spike protein mRNA, I guess) could quickly be synthesized.
To go from that to mass vaccination, even if we skip trials for efficacy and safety, requires that you know enough about how the virus and the vaccine behave within the body, to have some idea of where and how to administer the vaccine to a patient. Also, there needs to be infrastructure to mass-produce the vaccine, and a way to distribute it.
Complications known to me, in the case of Covid mRNA vaccines, are that Covid’s interaction with the body and the immune system is intricate and was not immediately understood (this matters in deciding how to introduce a vaccine into the body), and that mRNA vaccines currently require ultracold refrigeration for their distribution, an infrastructure that doesn’t even exist in some countries.
Let’s see a concrete counterfactual scenario for rapid deployment of a Covid mRNA vaccine in 2020, that takes into account these two factors; and then we can start to estimate how many extra lives the HCT ethos might have saved.
I can actually expand on this a little bit for you.
HCTs have been run in the past, but only for diseases where we had an efficacious treatment. The reason COVID HCTs would only have been run in the Phase 3 stage is because early in the pandemic, we had no proven-effective treatment.
This is a choice based on ethical and political reasoning, rather than science.
As Peter McCluskey points out, the choice not to begin an immediate mass-vaccination campaign with the untested mRNA vaccines we had on January 13th is likewise based on political and ethical reasoning, rather than a scientific choice. We now know, of course, that those vaccines were extremely effective. We’d have saved a colossal number of lives if we had. If we’d paused to run HCTs early on and then distributed the vaccines, we’d have still saved the vast bulk of lives that have been lost.
It’s only because our institutional leaders have made the ethical and political choices they have on our behalf that HCTs appear to be ineffective. We could have made different choices that were equally scientific, but based on different political and ethical reasoning. Continuing with our conventional ethical/political choice cost us over a million lives. Is it worth it? Medical ethicists disagree, none of the experts are talking about it enough, and it’s time for them to step it up and for The People to have a say.
OK, let’s talk about some of the issues that would arise in this scenario.
Taking an mRNA vaccine means becoming temporarily transgenic. mRNA for Covid spike protein is injected into your muscle cells, they produce it, and this stimulates antibody production.
In having trials, one is not only testing that the Covid mRNA vaccine is effective against Covid; one is also testing whether the vaccine itself has side effects.
Are you proposing to move straight to mass vaccination, without testing for vaccine side effects? But if not, how will making the trials HCTs, save time? HCTs are only different in the way that they test efficacy against the pathogen. When it comes to testing for side effects of the vaccine itself, don’t you have to wait just as long as you do, in a non-challenge trial?
Yes, I think there are basically three options:
Vaccinate with safety and efficacy data (conventional trials)
Vaccinate only with efficacy data (early HCTs)
Vaccinate with no data (immediate vaccination campaign on development of a vaccine)
I’m advocating that option 2 and option 3 be considered as realistic scientific, ethical, and political possibilities during the early stage of a deadly future pandemic akin to the one we face now.
Two of the questions I still have are:
What are the worst side effects of any vaccine that’s ever been tested?
How frequently do vaccines fail in conventional trials due to safety concerns?
This paper finds that 33% of tested vaccines have made it through all 3 trial phases. One of the worst consequences of a historically approved vaccine, used as an example by the AAMC of why we can’t rush a COVID-19 vaccine, was the polio vaccine where 120,000 doses contained live virus.
This caused ten deaths. Stack that up against over 1.6 million and counting.
Once again, I’m not strictly saying the AAMC is wrong. But they are begging the question. Comparing the historical base rate of deaths due to unsafe vaccines vs. the base rate of expected deaths due to COVID-19 is, on its face, a pretty reasonable and obvious approach to evaluating what we should do.
The AAMC glosses right over this issue. They must know it’s why many of their readers are looking up the article in the first place. So they’re choosing to ignore this line of thinking. I’m asking them to stop ignoring it.
If (2) and (3) were seriously considered, then I’d think you’d particularly want to avoid using only a single vaccine. From a civilizational point of view, the largest issue isn’t the expectation of the direct outcome—it’s that there’s a small chance you may have a bad outcome with very little variance across the population.
I’d be much less concerned about doing (2) or (3) with twenty different vaccines than with one.
Black Swan considerations definitely apply here. Although as far as I know, we haven’t had a vaccine that outright killed the majority of the people taking it, it’s not impossible. Maybe it’s just rare enough that we haven’t established a meaningful base rate. You’d also want to be concerned about the possibility of interactions from giving multiple vaccines to one person.
It might make sense to do something like vaccinating populations in the hardest-hit areas first, trying new vaccines as they become available, prioritizing the safest and most effective vaccines as data emerges.
If you want to make the case that with a different ethos, Covid-19 mortality might have been dramatically lower, it would help to exhibit a scenario in which this happens.
Much is being made of the fact that mRNA vaccines were first synthesized, very soon after the virus’s genetic sequence became available. But this just means that a particular molecular construct (a carrier for spike protein mRNA, I guess) could quickly be synthesized.
To go from that to mass vaccination, even if we skip trials for efficacy and safety, requires that you know enough about how the virus and the vaccine behave within the body, to have some idea of where and how to administer the vaccine to a patient. Also, there needs to be infrastructure to mass-produce the vaccine, and a way to distribute it.
Complications known to me, in the case of Covid mRNA vaccines, are that Covid’s interaction with the body and the immune system is intricate and was not immediately understood (this matters in deciding how to introduce a vaccine into the body), and that mRNA vaccines currently require ultracold refrigeration for their distribution, an infrastructure that doesn’t even exist in some countries.
Let’s see a concrete counterfactual scenario for rapid deployment of a Covid mRNA vaccine in 2020, that takes into account these two factors; and then we can start to estimate how many extra lives the HCT ethos might have saved.