Compared to 1947, there are many fewer things that you can do without permission, and many more people from whom you must seek permission. This naturally inhibits quick action.
Institutional incentives are all pointed towards caution, conservatism, and proceduralism. Undertaking decisive action to deal with a new situation is discouraged, and therefore these institutions are full of people without the disposition to even try.
I don’t have citations for these, but cf. Zvi’s entire series on moral mazes.
To these, we add a corona-specific factor, that we do not have enough vaccine doses to vaccinate everyone, so we have to ration and prioritise our doses. This, in turn, opens up vaccine prioritisation to political input, which means that the two factors mentioned above come to dominate, and we wind up with a vaccine plan which is maximally cautious, procedural, and bureaucratic. If we had enough doses to actually vaccinate everyone, it would be much easier to sell a policy of just vaccinating whoever walks through the door.
But why don’t we have enough doses to actually vaccinate everyone? The vaccines were designed almost a year ago; what we’ve done since then is test them to make sure they don’t have bad side-effects etc. I find it hard to believe that we can’t ramp up to a billion doses over the course of an entire year.
There’s been a dangerous impression communicated by the media over the last few months that these mRNA vaccines were “designed” a year ago, and that everything since then is just testing. That’s not really how drug development works, particularly for a brand new modality like this. It’s a multi-dimensional engineering challenge with many, many decisions downstream of the mRNA sequence that need to be made: how it’s manufactured, how much dose, how the sequence will be delivered in a carrier molecule, how the vaccine will be packaged. None of that can be done too far in advance, because the FDA approval is contingent on those details, and could require changes.
I’d be interested to hear more about this. I’m very skeptical, not of the claim that it’s a multi-dimensional engineering challenge etc. but of the claim that it couldn’t have been done substantially faster than it was.
Empirically speaking, this was already done substantially faster than any drug development process I can think of. The reason it was done relatively quickly was because as much work was done “at risk” as possible, supported by funding guarantees from the government. But that only gets you so far, and there just are steps in the development that need to be done sequentially, taking time. Happy to answer more specific questions.
Thanks! (Strong-upvoting for going against the conventional wisdom here, being polite, and willing to back it all up with discussion. I really hope you are right.)
Is that true? If not, when did large-scale production begin? I guess I want to know what sub-process took 10 months. Was it that they needed 10 months to build the new factories to build the vaccine, because old factories couldn’t be repurposed? Was it that old factories could be repurposed but need new equipment which couldn’t be 3D printed but had to be made in a traditional assembly line which needed to be purpose-built?
It claims that we could have had billions of doses several months ago, if we had been willing to pay the vaccine producers a few billion dollars more early on.
What is this “we” you are talking about? Vaccines aren’t cotton masks, where anyone with $200 of equipment and materials can make a dozen of them. Especially the mRNA version, which requires different equipment than the annual flu vaccine.
Plus, there were X different vaccines being pursued as of March 2020. 6 of them have now been approved (in various countries worldwide), but how many didn’t work out. The process of scaling from lab bench to factory is difficult and expensive, and that couldn’t even start until it is know which ones are going to work. (Or if someone was willing to spend the $$$ to develop every candidate in parallel. I don’t know how much that would have cost, but it didn’t happen.)
and that couldn’t even start until it is know which ones are going to work.
First of all, we totally could have started whilst still uncertain about which ones were going to work. The cost of starting and then stopping the ramp-up is probably at least an order of magnitude less than the cost of actually producing a billion doses. Given the stakes involved, the rational thing for humanity to do would be to ramp up multiple vaccines in parallel, so that at least one would be ready to go when it is proven safe.
Secondly, we didn’t need 10 months to know which ones were going to work. The FDA approval process is not the fastest way of determining whether a vaccine is sufficiently safe to be worth producing during a pandemic.
There were some government funded and philanthropic (gates I think) backstops, essentially guarantees of paying for losses if manufacturing before knowing if it worked turned out bad. There should have been more and faster, as pointed out by Cowen.
I remember reading around the beginning of the pandemic that Bill Gates was going to do exactly that: subsidize production of many different vaccine candidates with his own money, and accept the sunk cost for any vaccines that ended up not working. I haven’t seen anything about this idea recently though, and it seems he has not been (at least publicly) behind any vaccine production efforts. Any idea why? To avoid perceived competition with Operation Warp Speed?
You can get paid whether or not the vaccine gets approved by making contracts with governments that you provide the vaccine dosis that are not dependent on approval.
It’s just a matter of governments valuing vaccine doses enough to be willing to pay enough money for their production.
Option value. They’re not paying for a vaccine that can’t be used, they’re paying for a vaccine that MIGHT be usable in the near- or medium-term future. Paying for many options before approval so you’re ready with volume for the one(s) that get approved is +EV in most scenarios.
I’m honestly surprised by someone on LessWrong engaging in that kind of Black White thinking. If you are uncertain about whether or not a given vaccine gets approved, there’s a probability of it getting approved and you can calculate expected utility given the cost you pay for the vaccines that might or might not be approved.
Is the idea of thinking in terms of probability new to you, or is there some way that using it in a political context is hard?
The question was “why didn’t we ramp up sooner?”. I answered the question as best I knew how. Everyone is acting like I’m the one that decided to not use option pricing.
And yes, government paying for things that might not work is hard. Besides generic mind killing, there are people that don’t want the government to spend money and the people who don’t believe in vaccines at all. They all vote.
A few observations:
Compared to 1947, there are many fewer things that you can do without permission, and many more people from whom you must seek permission. This naturally inhibits quick action.
Institutional incentives are all pointed towards caution, conservatism, and proceduralism. Undertaking decisive action to deal with a new situation is discouraged, and therefore these institutions are full of people without the disposition to even try.
I don’t have citations for these, but cf. Zvi’s entire series on moral mazes.
To these, we add a corona-specific factor, that we do not have enough vaccine doses to vaccinate everyone, so we have to ration and prioritise our doses. This, in turn, opens up vaccine prioritisation to political input, which means that the two factors mentioned above come to dominate, and we wind up with a vaccine plan which is maximally cautious, procedural, and bureaucratic. If we had enough doses to actually vaccinate everyone, it would be much easier to sell a policy of just vaccinating whoever walks through the door.
But why don’t we have enough doses to actually vaccinate everyone? The vaccines were designed almost a year ago; what we’ve done since then is test them to make sure they don’t have bad side-effects etc. I find it hard to believe that we can’t ramp up to a billion doses over the course of an entire year.
There’s been a dangerous impression communicated by the media over the last few months that these mRNA vaccines were “designed” a year ago, and that everything since then is just testing. That’s not really how drug development works, particularly for a brand new modality like this. It’s a multi-dimensional engineering challenge with many, many decisions downstream of the mRNA sequence that need to be made: how it’s manufactured, how much dose, how the sequence will be delivered in a carrier molecule, how the vaccine will be packaged. None of that can be done too far in advance, because the FDA approval is contingent on those details, and could require changes.
I’d be interested to hear more about this. I’m very skeptical, not of the claim that it’s a multi-dimensional engineering challenge etc. but of the claim that it couldn’t have been done substantially faster than it was.
Empirically speaking, this was already done substantially faster than any drug development process I can think of. The reason it was done relatively quickly was because as much work was done “at risk” as possible, supported by funding guarantees from the government. But that only gets you so far, and there just are steps in the development that need to be done sequentially, taking time. Happy to answer more specific questions.
Thanks! (Strong-upvoting for going against the conventional wisdom here, being polite, and willing to back it all up with discussion. I really hope you are right.)
OK, here goes: This diagram makes it seem that large-scale production only began after Phase II completed: https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/covid-19-vaccines-development-evaluation-approval-monitoring
Is that true? If not, when did large-scale production begin? I guess I want to know what sub-process took 10 months. Was it that they needed 10 months to build the new factories to build the vaccine, because old factories couldn’t be repurposed? Was it that old factories could be repurposed but need new equipment which couldn’t be 3D printed but had to be made in a traditional assembly line which needed to be purpose-built?
Why did it took from Feb 24 when Moderna shipped their vaccines to the NIH till Mar 16 till they vaccines where given to a patient?
Why did the phase 1 trial only start Mar 27?
What do you think about this: https://marginalrevolution.com/marginalrevolution/2021/01/fact-of-the-day-get-to-those-rooftops.html?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+marginalrevolution%2Ffeed+%28Marginal+Revolution%29
It claims that we could have had billions of doses several months ago, if we had been willing to pay the vaccine producers a few billion dollars more early on.
What is this “we” you are talking about? Vaccines aren’t cotton masks, where anyone with $200 of equipment and materials can make a dozen of them. Especially the mRNA version, which requires different equipment than the annual flu vaccine.
Plus, there were X different vaccines being pursued as of March 2020. 6 of them have now been approved (in various countries worldwide), but how many didn’t work out. The process of scaling from lab bench to factory is difficult and expensive, and that couldn’t even start until it is know which ones are going to work. (Or if someone was willing to spend the $$$ to develop every candidate in parallel. I don’t know how much that would have cost, but it didn’t happen.)
We = humanity. Or the USA, if you prefer.
First of all, we totally could have started whilst still uncertain about which ones were going to work. The cost of starting and then stopping the ramp-up is probably at least an order of magnitude less than the cost of actually producing a billion doses. Given the stakes involved, the rational thing for humanity to do would be to ramp up multiple vaccines in parallel, so that at least one would be ready to go when it is proven safe.
Secondly, we didn’t need 10 months to know which ones were going to work. The FDA approval process is not the fastest way of determining whether a vaccine is sufficiently safe to be worth producing during a pandemic.
There were some government funded and philanthropic (gates I think) backstops, essentially guarantees of paying for losses if manufacturing before knowing if it worked turned out bad. There should have been more and faster, as pointed out by Cowen.
I remember reading around the beginning of the pandemic that Bill Gates was going to do exactly that: subsidize production of many different vaccine candidates with his own money, and accept the sunk cost for any vaccines that ended up not working. I haven’t seen anything about this idea recently though, and it seems he has not been (at least publicly) behind any vaccine production efforts. Any idea why? To avoid perceived competition with Operation Warp Speed?
They can’t ramp up until they are approved. You don’t make a billion doses only to discover a year later you aren’t going to get paid for them.
You can get paid whether or not the vaccine gets approved by making contracts with governments that you provide the vaccine dosis that are not dependent on approval.
It’s just a matter of governments valuing vaccine doses enough to be willing to pay enough money for their production.
I mean....sure.
But why would the government, or anyone, pay for a vaccine that couldn’t be used? An unapproved vaccine does nothing for anyone.
Option value. They’re not paying for a vaccine that can’t be used, they’re paying for a vaccine that MIGHT be usable in the near- or medium-term future. Paying for many options before approval so you’re ready with volume for the one(s) that get approved is +EV in most scenarios.
Which is why we proposed exactly that, at the end of April: https://www.lesswrong.com/posts/uXb4gcDP2fgBPcMHJ/market-shaping-approaches-to-accelerate-covid-19-response-a
Now published: https://f1000research.com/articles/9-1154
Unfortunately, we couldn’t get policymakers on board.
I’m honestly surprised by someone on LessWrong engaging in that kind of Black White thinking. If you are uncertain about whether or not a given vaccine gets approved, there’s a probability of it getting approved and you can calculate expected utility given the cost you pay for the vaccines that might or might not be approved.
Is the idea of thinking in terms of probability new to you, or is there some way that using it in a political context is hard?
The question was “why didn’t we ramp up sooner?”. I answered the question as best I knew how. Everyone is acting like I’m the one that decided to not use option pricing.
And yes, government paying for things that might not work is hard. Besides generic mind killing, there are people that don’t want the government to spend money and the people who don’t believe in vaccines at all. They all vote.
This is a problem that a more competent society would have solved easily.
How?
If you want to eliminate testing and government approval, I’d be willing to have that conversation. I don’t think many would though.
Why would anyone pay to ramp up production on something that might not do anything? Or might even make thins worse?
Because it might do something sufficiently important that the benefit * probability of benefit outweighs the cost.