Here’s a fun modified version of the trolley problem: You are cruising along in the Trolley, as one does, and look ahead to see 2.6 million people on the tracks; the Trolley is set to roll over all of them. To be fair, you are only guessing at that 2.6 million figure - the Trolley is still distant enough that your best estimate is probably somewhere between one and five million; it will only be later that you learn the exact figure, but it’s by no means unclear that you are dealing with “population of a major metropolis” type numbers on your current track.
Anyway, to step back remember the function of a bureaucracy is to maintain the bureaucracy. And the fact that it is populated by scientists and not clerks doesn't change this. The head of the organization is there because someone thought they would be good for that organization. This is not the same as achieving the goals you think that organization should.
Normally there will be some alignment with an orgs stated goals because it's authority is based on this perception. But in a crisis executive decision making is required which may put the org at risk, this is the conflict.
So the result is the political response of mitigation (mask, social distancing...) and the vaccine decision can be made by existing protocol. The rest is just power networking which your dept heads know how to do.
I would ditch the trolley intro or keep riding. The way you changed gears was kind of harsh.
I'm old enough that the thalidomide babies were children at the same time as me. I vaguely recall attending school with one of them, and met another as an adult.
Obviously this is not a case of vaccines gone wrong - it was a drug given to pregnant women, prescribed for morning sickness among other things.
I also don't have to go far to find all kinds of (ahem) snake oil - products sold with carefully written non-claims of effects they don't actually have, plus the (true) claim that they can't just say explicitly what the product supposedly does, because of FDA rules.
That doesn't mean that the FDA was right in this case - and they do seem to have confused "we didn't personally develop/vet it" with "this shouldn't be used" during this epidemic (e.g. with regard to covid tests, early on).
And bureaucracy tends to grow beyond what's actually needed, as well as tending to impose additional costs. But I'm nonetheless grateful that the FDA was involved in approving treatments I'm receiving (not related to covid).
I also don't especially trust big pharma. The incentives for almost any executive insulate them from significant bad consequences if they make decisions that kill people; relatively recent PG&E behaviour comes to mind. (They saved so much money not doing maintenance that it was a great business decision, increasing the stock price - until there was a fire, and deaths, and lawsuits, and bankruptcy - none of which affected any profits the executives had already taken - and quite likely also didn't affect their future employment prospects.)
Of course the other thing about "challenge trials" is they presume that vaccines are binary - they either protect or don't. You presumably can't (ethically)/won't challenge unvaccinated controls, so you don't know how many unvaccinated people would (not) have caught covid with the same challenge procedure. If any vaccinated person winds up with covid - and I presume some will, even with 95% effectiveness - you're left guessing how many is too many, in judging the vaccine to be (in)effective.
You say that the current mRNA vaccines were both: 1, pretty much sure to work, and 2. had only a small chance of not working. What are you basing those assumptions on?
For 1, we've never had a mRNA vaccine used successfully on humans. Ever. In the history of the world. To claim that they were "pretty much sure to work" seems like hindsight bias.
For 2, here's a paper in Nature that shows that only about 20% of vaccine candidates make it through all phases of testing.
Now, you chose to ask only for failed vaccine launches, and of course there aren't many! That's what all of the phases are for, the ones that weed out the 4 out of every 5 vaccine candidates that just don't work! Again, thinking that we should have had more than a ~20% expectation of these vaccines working is hindsight bias.
Could the FDA have moved faster? Absolutely, and hopefully they will in the future with the information that we now know. But transposing our current understanding of mRNA vaccines onto the world as it was January 2020 is a recipe for bias.
An important thing to remember here is that most of the time, the FDA is approving something that's not so urgent--yet another antidepressant that will maybe work a little better than the existing ones for some patients, a new statin that might be a good choice for folks who get bad side effects on the existing ones, etc. The super-cautious process might be pretty reasonable for those drugs, where the available benefit is really small. It's just not very reasonable for a once-every-few-decades global pandemic that's set to kill millions of people.
Great post. The trade off seems even worse for the case of the FDA and rapid testing. I don't think there is any risk of harm from a paper strip test. Just a few days ago the FDA announced that they're taking steps to "streamline" the path for screening tests. They say this over a year into the pandemic. We had a dozen of these tests developed and ready for production last May. How can they say "streamline" with a straight face?!
Unrelated to covid - In a recent seminar class on the epidemiology of cardiovascular disease, a guest lecturer discussed the role of the FDA in the development of CVD treatments. He talked about type 2 diabetes and the current rule that states that even after a drug is approved as safe and efficacious for treating T2DM and enters the market, the drug company must continue to do trials to assess risk of CVD outcomes. The speaker claimed that this was a great step because "pharmaceutical companies clearly wouldn't do this on their own." Aside from the fact that this sounds like an empirical question, I get the sense that many proponents of the FDA share this belief. Why do so many presume that in a world without an FDA there would be no clinical trials, or that every company would just start selling snake oil? What could be worse for the stock price of a pharma company than news that a drug harms people and that executives knew about it? Once Moderna and Pfizer developed the vaccine, why would they sell it to anyone if they weren't extremely confident that it wouldn't seriously harm anyone? Just as consumers demand safer cars, wouldn't consumers demand safer drugs? Why wouldn't drug companies have a third party conduct clinical trials and make public the results? Why would consumers want to take a drug that hasn't released results of clinical trials? And wouldn't competition and lower barriers to entry reinforce this? There are many other variables including the patent system and the fact that the patient isn't always the one who directly pays for the drug. Perhaps, I don't understand the full argument, but I've never understood why people believe that in a world without an FDA there would be no rigorous trials. Do we have evidence for this? Any thoughts?
What I'd really like to see is this argument (or a response to this argument) (or really anything on this subject) from someone who works at the FDA, or a similar regulatory agency. Because then we could get more informed criticism, and a more detailed accounting of how FDA made the decisions it did and what sort of institutional incentives need to be tweaked to change how it operates in the future. I don't have a good understanding of that.
Also, it's not as simple as arguing that FDA should approve drugs faster. FDA has at times been much too quick to approve drugs with serious side effects or drugs that have no real benefit (Vioxx, Sarafem). I'd like to see them do better cost-benefit analysis, and keep the interests of patients at the center—i.e., our real interests, not what the medical ethicists say our interests are.
RC, I like that you liked your own comment :).
Anyway, to step back remember the function of a bureaucracy is to maintain the bureaucracy. And the fact that it is populated by scientists and not clerks doesn't change this. The head of the organization is there because someone thought they would be good for that organization. This is not the same as achieving the goals you think that organization should.
Normally there will be some alignment with an orgs stated goals because it's authority is based on this perception. But in a crisis executive decision making is required which may put the org at risk, this is the conflict.
So the result is the political response of mitigation (mask, social distancing...) and the vaccine decision can be made by existing protocol. The rest is just power networking which your dept heads know how to do.
I would ditch the trolley intro or keep riding. The way you changed gears was kind of harsh.
I'm old enough that the thalidomide babies were children at the same time as me. I vaguely recall attending school with one of them, and met another as an adult.
Obviously this is not a case of vaccines gone wrong - it was a drug given to pregnant women, prescribed for morning sickness among other things.
I also don't have to go far to find all kinds of (ahem) snake oil - products sold with carefully written non-claims of effects they don't actually have, plus the (true) claim that they can't just say explicitly what the product supposedly does, because of FDA rules.
That doesn't mean that the FDA was right in this case - and they do seem to have confused "we didn't personally develop/vet it" with "this shouldn't be used" during this epidemic (e.g. with regard to covid tests, early on).
And bureaucracy tends to grow beyond what's actually needed, as well as tending to impose additional costs. But I'm nonetheless grateful that the FDA was involved in approving treatments I'm receiving (not related to covid).
I also don't especially trust big pharma. The incentives for almost any executive insulate them from significant bad consequences if they make decisions that kill people; relatively recent PG&E behaviour comes to mind. (They saved so much money not doing maintenance that it was a great business decision, increasing the stock price - until there was a fire, and deaths, and lawsuits, and bankruptcy - none of which affected any profits the executives had already taken - and quite likely also didn't affect their future employment prospects.)
Of course the other thing about "challenge trials" is they presume that vaccines are binary - they either protect or don't. You presumably can't (ethically)/won't challenge unvaccinated controls, so you don't know how many unvaccinated people would (not) have caught covid with the same challenge procedure. If any vaccinated person winds up with covid - and I presume some will, even with 95% effectiveness - you're left guessing how many is too many, in judging the vaccine to be (in)effective.
You say that the current mRNA vaccines were both: 1, pretty much sure to work, and 2. had only a small chance of not working. What are you basing those assumptions on?
For 1, we've never had a mRNA vaccine used successfully on humans. Ever. In the history of the world. To claim that they were "pretty much sure to work" seems like hindsight bias.
For 2, here's a paper in Nature that shows that only about 20% of vaccine candidates make it through all phases of testing.
https://www.nature.com/articles/nbt0596-591.pdf?origin=ppub
Now, you chose to ask only for failed vaccine launches, and of course there aren't many! That's what all of the phases are for, the ones that weed out the 4 out of every 5 vaccine candidates that just don't work! Again, thinking that we should have had more than a ~20% expectation of these vaccines working is hindsight bias.
Could the FDA have moved faster? Absolutely, and hopefully they will in the future with the information that we now know. But transposing our current understanding of mRNA vaccines onto the world as it was January 2020 is a recipe for bias.
An important thing to remember here is that most of the time, the FDA is approving something that's not so urgent--yet another antidepressant that will maybe work a little better than the existing ones for some patients, a new statin that might be a good choice for folks who get bad side effects on the existing ones, etc. The super-cautious process might be pretty reasonable for those drugs, where the available benefit is really small. It's just not very reasonable for a once-every-few-decades global pandemic that's set to kill millions of people.
Great post. The trade off seems even worse for the case of the FDA and rapid testing. I don't think there is any risk of harm from a paper strip test. Just a few days ago the FDA announced that they're taking steps to "streamline" the path for screening tests. They say this over a year into the pandemic. We had a dozen of these tests developed and ready for production last May. How can they say "streamline" with a straight face?!
Unrelated to covid - In a recent seminar class on the epidemiology of cardiovascular disease, a guest lecturer discussed the role of the FDA in the development of CVD treatments. He talked about type 2 diabetes and the current rule that states that even after a drug is approved as safe and efficacious for treating T2DM and enters the market, the drug company must continue to do trials to assess risk of CVD outcomes. The speaker claimed that this was a great step because "pharmaceutical companies clearly wouldn't do this on their own." Aside from the fact that this sounds like an empirical question, I get the sense that many proponents of the FDA share this belief. Why do so many presume that in a world without an FDA there would be no clinical trials, or that every company would just start selling snake oil? What could be worse for the stock price of a pharma company than news that a drug harms people and that executives knew about it? Once Moderna and Pfizer developed the vaccine, why would they sell it to anyone if they weren't extremely confident that it wouldn't seriously harm anyone? Just as consumers demand safer cars, wouldn't consumers demand safer drugs? Why wouldn't drug companies have a third party conduct clinical trials and make public the results? Why would consumers want to take a drug that hasn't released results of clinical trials? And wouldn't competition and lower barriers to entry reinforce this? There are many other variables including the patent system and the fact that the patient isn't always the one who directly pays for the drug. Perhaps, I don't understand the full argument, but I've never understood why people believe that in a world without an FDA there would be no rigorous trials. Do we have evidence for this? Any thoughts?
What I'd really like to see is this argument (or a response to this argument) (or really anything on this subject) from someone who works at the FDA, or a similar regulatory agency. Because then we could get more informed criticism, and a more detailed accounting of how FDA made the decisions it did and what sort of institutional incentives need to be tweaked to change how it operates in the future. I don't have a good understanding of that.
Also, it's not as simple as arguing that FDA should approve drugs faster. FDA has at times been much too quick to approve drugs with serious side effects or drugs that have no real benefit (Vioxx, Sarafem). I'd like to see them do better cost-benefit analysis, and keep the interests of patients at the center—i.e., our real interests, not what the medical ethicists say our interests are.