[GavinB]

So no, we did not “have the vaccine” in February.

We did have it, we just didn't know which one it was. And we refused to risk any individual life in order to potentially save hundreds of thousands or more.

We also could have invested single digit billions early on to build capacity for all of these different potential vaccines, but we decided to play if "safe" and will now be spending over a trillion again to try to save the economy.

I don't blame the pharma companies for this. Our government and medical establishment was not intellectually prepared to make the hard decisions required to save us. And we need to be building momentum to learn how to do better.

[wahern]

> we refused to risk any individual life in order to potentially save hundreds of thousands or more.

The concern wasn't Trolley problem[1] paralysis, where authorities are afraid to deliberately shift harm to a minority to protect a majority. The concern was vaccine-associated disease enhancement (VADE), which could possibly cause more overall harm and deaths than simply doing nothing at all. It's a significant and legitimate concern because not only has it happened before with released vaccines, it has been a particular problem in SARS vaccine research and trials for 20 years. See "Learning from the past: development of safe and effective COVID-19 vaccines", https://www.nature.com/articles/s41579-020-00462-y

We had complete candidate vaccines mere days into the outbreak, but nobody was sure they were safe because they were just the latest iterations in long lines of similar candidate vaccines, all eventually failing. They couldn't rush trials too quickly because VADE situations might not become apparent without a large pool tracked over an extended period of time so that you can see what happens with reinfections, etc.

We got lucky. It seems to be the case that we had just recently turned the corner in resolving many of these barriers. If were were facing COVID-10 (i.e. a SARS pandemic in 2010), we'd be screwed because in 2010 we were much further away from figuring out how to avoid VADE-like failures in SARS vaccines.

[1] https://en.wikipedia.org/wiki/Trolley_problem

[Robotbeat]

Actual it was trolley problem paralysis. We could've gotten a much larger sample size much earlier (and with challenge trials, in addition to other methods) to screen out the very thing you're mentioning here (VADE).

[wahern]

Trials were accelerated. Anyhow, the whole premise that excessively cautious American and European regulations delayed testing is flawed. This is a global problem, and there are plenty of countries with far less onerous regulatory requirements, or with less apprehensive populations more willing to volunteer. It's no coincidence that many of these trials have occurred in other countries like Brazil.

[wahern]

Speaking of apprehensive populations, there's another concern on the mind of health authorities--managing the next pandemic. Say a vaccine has VADE or similar ill effects on some small but substantial part of the population. Even if the overall benefit in harm reduction is clearly superior, you may end up destroying trust. Even if your regulatory authorities are cold, calculating, utilitarian, econometric philosopher-kings, the population is not. The next pandemic might be worse, or social trust might continue to tank. Maximizing the long-term utility function might require a level of risk averseness that seems irrational in the present.

[Robotbeat]

That's why you start out with early, large-n testing so you have a long baseline of good quality data. With volunteers, not the general public.

[creato]

Isn't this exactly what happened?

[BurningFrog]

Would results from trials breaking western ethical norms be accepted by FDA?

[Robotbeat]

The risks would be no greater than others done for national defense. In a pandemic? Yeah.

[BurningFrog]

The US Army would do it, sure.

The FDA works in a whole other way.

[JamesBarney]

Why does natural infection allow us to rule out VADE while challenge trials don't?

[wahern]

Phase III trials for both the Pfizer and Moderna vaccines actually began in late July, a mere 4 months after declaration of the pandemic. Challenge trials were unnecessary because they wouldn't have actually sped things up. By the time of the phase III trials you could already expect vaccinated individuals to be challenged via natural infection. And I'll bet money that the Pfizer and Moderna vaccines were, as a practical matter, given a green light by the FDA when the first early phase III results came back, months before formal approvals (which actually came in the middle of the phase III trials); meaning there would've been no regulatory risk to pushing the manufacturing pipeline into maximum overdrive.

There have been plenty of fumbles and mistakes all around, but I don't understand how people don't appreciate how incredibly fast the process has already been.

IMO, the real issues involve more mundane matters of logistics--coordination, resource allocation, etc. Could the process have gone faster? Probably. Not because of safety protocols or inflexible regulations, but because we had unforced errors starting and executing trials. For example, AFAICT, trials could have started in Brazil in early June, but presumably didn't because the companies needed more time to spin things up. And of course manufacturing and distribution of the vaccine should be going much smoother. Pharmaceutical companies and, especially, governments should have thrown more resources toward growing the supply chain of machinery; it was foreseeable from the beginning because of the manifest deficiencies in the supply chain for personal protection equipment, ventilators, etc, all of which made evident the need to retool industries to be able to scale manufacturing. And governments have had almost an entire year to figure out distribution protocols, but instead it seems officials across the board in the U.S. simply assumed it would be sufficient to push vaccines through existing healthcare networks, despite the fact they're notoriously byzantine and inefficient, especially for something so time critical, and especially given the need for consistency and uniformity across the population.

Is COVID-19 providing cautionary tales regarding government intervention in the free market? Absolutely. Not because governments have been intervening too much, but because they've been intervening too little; not because it has proven government more inept than private enterprise, but because private enterprise is intrinsically incapable of achieving alone the level of coordination needed to scale our response in the time required, yet we have shown ourselves too politically and fiscally risk averse to wield the tools of government in an emergency. It's like the delayed and anemic Katrina response, writ large.

[JamesBarney]

> And I'll bet money that the Pfizer and Moderna vaccines were, as a practical matter, given a green light by the FDA when the first early phase III results came back, months before formal approvals (which actually came in the middle of the phase III trials); meaning there would've been no regulatory risk to pushing the manufacturing pipeline into maximum overdrive.

If this is true this is the most insane thing I've ever heard.

They can't have it both ways. You can't say "the FDA knew it was safe and effective so they gave the geeen light to the manufacturers" and also "they had to withhold this vaccine from the population because they didn't know if it was safe and effective".

> Is COVID-19 providing cautionary tales regarding government intervention in the free market?

I don't believe criticism of the government needs to be condensed into "government intervention good" or "government intervention bad".

I don't think the solution is smaller government or bigger government it's better government.

The FDA has royally fucked up over and over again by being far too cautious. A lot of the government fucked up when they said masks didn't work.

The CDC fucked up when they promoted vaccinating essential workers instead of the old.

And the executive branch has been far too cautious and uninvolved in ensuring we have enough high quality masks, and broadening vaccine the pipeline.

[standardUser]

To be fair, part of the reason we establish rules of ethics is so that when an emergency happens, we don't just wing it and start making up the rules. Situations like this pandemic are a very good reason to revisit established rules of ethics, but using it as justification to overrule existing rules negates the entire idea of establishing rules of ethics in the first place.

[GavinB]

I agree in principle. On the other hand, global crises have always called for extraordinary measures.

Even in this pandemic, we've (correctly, I would say) basically thrown out important principles like freedom of movement and freedom of association during lockdowns. I think that allowing volunteers to put themselves at a relatively low risk to speed up vaccine trials would have been a relatively small transgression, compared to the lockdowns and travel bans (which, again, I think were justified).

But I do take your point.

[cameldrv]

This is a very good point. The lockdown measures, while very arguably necessary, are an extremely severe measure. They were perhaps the only measure that would have been effective at the beginning when there was no preparation.

Yet, things like enforced mask wearing, or enforced out of home quarantine/isolation somehow were off the table. It is a weird path-dependent quirk of the fact that we had no testing at the beginning, that instead of quarantining and isolated the exposed and infected, we are effectively quarantining everyone.

[raphaelj]

Isn't it exactly what happened? Some vaccines started large scale tests around March/April.

It's just that you have to wait a few months to know if the vaccine you're testing is effective. You can't make this delay shorter with more volunteers.

And when you're fighting a decease that "only" kills 0.5% of the people inflected, your risk margin is pretty low (what if your vaccine creates deadly consequences to 0.6% of the people vaccinated?).

[maxerickson]

Challenge trials shorten the period by intentionally exposing the volunteers to the infection.

The mRNA vaccines had to wait until November to get enough infections.

There can be an issue that the measurement of the effectiveness of the vaccine is then related to the exposure protocol (which may not be the same as typical natural infections), but it's reasonable to expect results much sooner.

[andreareina]

So, you'd have to tell the participants that they're going to be deliberately exposed to the virus; I don't think you're going to get a representative sample of the population agreeing to that.

[sterlind]

People volunteer for military service even during wars, but you're right. Challenge trials won't be brimming with 75-year olds, the same way 75-year olds don't enlist. You'd learn that the vaccine works on healthy 20-somethings though, and that might have been enough for approval.

[maxerickson]

Yeah, I dunno. I don't see why there couldn't be a challenge arm to a trial that also did a larger group with no challenges.

The challenge arm wouldn't have any influence over the other arm (and likely not much impact on recruitment), but might provide results for some groups much faster. Starting vaccinations on younger healthcare workers in August seems like it would have been a win (assuming they had data to justify it by that point).

[BurningFrog]

You can recruit the demographics you need by paying them enough.

Challenge trials need far fewer people, so paying each one $1M is feasible.

[jbullock35]

> We also could have invested single digit billions early on to build capacity for all of these different potential vaccines

As of the end of October, the U.S. had invested $18 billion to "build capacity," mainly by making advance purchases of vaccines that had yet to be produced (and had yet to pass clinical trials). See [1]. But maybe you're thinking of building capacity in a different way.

> We refused to risk any individual life in order to potentially save hundreds of thousands or more.

This is such an important point. In particular, human challenge trials, in which healthy, low-risk volunteers are infected with a low dose of the virus, could have saved tens of thousands of lives -- at a minimum -- in the U.S. alone. The case for HCTs, including the ethical case, is taken up in [2].

In a comment below, someone likens HCTs to the infamous Tuskegee syphilis study. The comparison isn't apt. In the Tuskegee study, people infected with syphilis were promised medical care that they were later denied. When they were diagnosed with syphilis, they weren't even told of the diagnosis. Those conditions are a world apart from the HCTs that Eyal et al. propose in [2]. - - - - -

[1] https://www.bloomberg.com/news/features/2020-10-29/inside-op...

[2] https://academic.oup.com/jid/article/221/11/1752/5814216

[Gatsky]

I don't think challenge trials would have really helped much. The issue is that obtaining an accurate estimate of vaccine efficacy in the real world is a crucial piece of information. There is a very large difference between a 95% effective and a 70% effective vaccine in terms of the roll out and who/how many need to be vaccinated. Additionally, challenge trials are fundamentally contrived in terms of the innoculum size and mode of transmission. There is no substitute for a proper randomised trial under native transmission conditions. Challenge trials would lead us into a long night of uncertainty about efficacy.

[WalterBright]

Even worse, the rate of vaccine development and production seems to be falling behind the rate of covid mutation.

I.e. the way we do things means we cannot stop covid.

[maxerickson]

That's not evident at all. The vaccines appear to be effective enough against the existing 'notable' mutations, and we don't really have much information about what rate of concerning mutations to expect.

And then on the other side of it, Moderna has a vaccine against the South African mutation in a trial. And production capacity on the mRNA vaccines is pretty clearly not maxed out in any long term sense (and then the other vaccines apparently have a better path to volume; J&J still sounds like they will make 1 billion vaccines this year. The viral vector vaccines aren't as immediately adjustable as the mRNA vaccines, but they are similarly targeted, choosing a protein to be expressed).

[WalterBright]

There's talk in the press about the vaccines being less effective on the mutations.

In any case, the more people who are vaccinated, the more likely a strain will arise that is not affected by the vaccine. This will reset all the vaccination efforts back to zero.

This is what I am referring to.

[maxerickson]

They have reduced but sufficient effectiveness against the mutations that are in the news.

I guess there's lots of room for arguing about definitions, but I think we don't go back to zero if there is a vaccine escape. The production capacity that has been built in the last year is a big step forward (and we can expand it), and we are building out the administrative capacity to get the vaccine in people's arms (capacity that won't just vanish).

[jimbokun]

> We also could have invested single digit billions early on to build capacity for all of these different potential vaccines

Are we sure "we" didn't? I don't know the actual numbers behind what was spent ahead of time for the various vaccines, but I believe the manufacturing process was ramped up before the trials completed.

[GavinB]

There was discussion of it early on, but there's no evidence that it was done on any significant scale outside of the efforts of individual pharma companies working on their own supply chains.

It's possible that I'm wrong! Maybe we invested everything possible and couldn't have done significantly more. But it's striking that this article doesn't even address that question.

Basically, I haven't seen any evidence that this take is wrong: https://thezvi.wordpress.com/2021/01/28/covid-bill-gates-and...

[_carbyau_]

I am not entirely sure I agree with the thinking though.

While initial production ramp up would get the richer countries vaccinated quickly it seems like Gates has a more holistic picture and wants to see the whole world vaccinated faster.

I agree with this thinking. It won't matter if rich countries are vaccinated if other countries are coming up with new variations all the time. We want to eradicate this by having everyone in the world on the same page, not have it hanging around like the flu.

[natechols]

Oh thanks I was looking for followup on the Gates thing, that blog post is superb. And depressing.

[maxerickson]

The economists that put together this working paper estimated that we left a lot on the table. Several months and hundreds of billions of dollars in the US (that invested a relatively large amount) and nearly a year and over a trillion dollars for the globe. Table 1 on page 6 summarizes it.

https://bfi.uchicago.edu/wp-content/uploads/2021/01/BFI_WP_2...

[Gatsky]

The virus can be controlled with appropriate measures to limit the death rate - see Taiwan, SK, Australia, New Zealand etc. If you want to argue that we could have saved hundreds of thousands of lives I would probably start there instead of experimenting on billions of people.

[_carbyau_]

While this is true (I live in Melbourne Australia) it did affect a lot of people - financially, mentally etc.

Depending on where in society you sit probably shapes whether you think it was worth it. (Full disclosure, I do but I was also not inconvenienced much.)

As it stands currently, I note that interventions in Australia are much faster now.

Our stand down position was we had to wear masks to the supermarket and on public transport. Everywhere else was pretty close to normal.

But one case detected yesterday in our 4 million population city, means we all wearing masks whenever we're indoors today.

That one case has flicked that switch overnight. So it seems that the main thing is to test well and react quickly.

[peytn]

It likely helps to be a bit remote. That’s why Australia is free of other viruses like rabies.

[eloff]

An island at the edge of the world with more sheep than people is not at all comparable with the US or Europe.

If they'd acted early and decisively like the countries you mentioned, the outcome would likely have been better. But it would still look very different from those countries.

[Gatsky]

Yes, that's my point - the outcome would have been better, less people would have died. Italy was there as a stark warning, to the point where it was obvious that provinces with stricter controls did better than those without.

The USA had the poorest performance. When a country can't attend to basic matters of engaging with reality and protecting its citizens, despite incredible resources, it is defunct.

I am going to rant here. This virus is really an indictment on the state of the world. It seems inevitable now that it will be endemic, and due to the infectivity and presence of animal hosts, will not be eradicable. This is terribly disappointing. Consider that this is the year we gifted an entirely new disease to all the billions of people that will live in the future. We just increased by 1 the number of things that can make you sick and kill you. Think about HIV - if we could go back and stop HIV from spreading, with the benefit of 40 years of hindsight, we absolutely would have done that, no question, not for one minute. The economic saving alone is compellingly enormous, not accounting for the amount of suffering that would have been avoided. To me, all this calculus about economic activity and mental health versus stopping the virus is so short-sighted and missing the point entirely. It seems obvious to me that any degree of short term pain is a mere blip compared to how many people will suffer and die of the virus over the next 20 years because we let it out. We had one chance, one moment to stop this virus and we blew it. Everyone, every country, ever politician, blew it. I know it could have emerged in a few years, or there could be another virus next year but that doesn't change the fact that we could have stopped this one.

[eloff]

Yeah, I agree. I also sympathize with your rant and feel our politicians in the West, nearly without exception, let us all down and continue to do so. They failed to demonstrate any kind of preparation or logical science based response and continue to fail at that.

[Clewza313]

China has it under control (yes, seriously, it's not just CCP propaganda) and they have over a billion people. So do many other countries like Vietnam.

[umeshunni]

China (and Vietnam and SK) did this successfully with extremely strict lockdown rules. I'm not sure those would have been accepted in the West.

Arguably the West handled in the worst of both outcomes - arbitrary and incomplete lockdowns - that caused a huge financial toll and a huge human toll.

[eloff]

Unfortunately that only works when there's no guarantee of freedoms by the government. No free country was able to do a lockdown that strictly and effectively.

We do pay a price for those freedoms sometimes in times of crises - but there's no doubt which system we'd rather live under.

[midasuni]

NZ locked down at the point the U.K. was in the 50k new infections a day range.

They had an extra month of warning compared to Europe, that made a big difference.

[eloff]

And a lot less people traveling back and forth between hot spots.

[midasuni]

Even ignoring the tens of thousands of people crossing the uk-france border daily, heathrow alone sees (saw) immense transfer traffic that airports like Sydney and Auckland don’t.

[milliondollar]

EXACTLY my question. How much would it have cost to make some bets against the various types of vaccines that could come out. Make a "generic" manufacturing facility that could then help scale up. So what if we "wasted" $10B on facilities that didn't pan out?

[azangru]

> And we refused to risk any individual life in order to potentially save hundreds of thousands or more

But we are risking individual lives now. Vaccines have side effects. It's never about an individual life, always a calculus of number of lives risked vs number of lives saved, I would think.

[mortehu]

I think the point is that we chose and are still choosing to wait for a hundred people to get infected at random in each efficacy trial, instead of just deliberately infecting a hundred people immediately.

The cost of our approach is that roughly the same proportion of the country's population must bet infected as in the trials.

[Digit-Al]

So, would you volunteer to be deliberately infected with a disease that might or might not kill you in order to save many other lives?

[mortehu]

Tens of thousands of people have signed up for this at 1daysooner.org. I didn't even volunteer for any of the ongoing trials myself.

[doliveira]

Honestly, I would. The way things are going down here in my country (Brazil) I will get infected eventually, at least by participating in challenge trials it would help other people.

[ClumsyPilot]

That's an difficult and potentially eternal question - some people volunteer to go to space or cross the ocean on a canoe because to them its worth the risk. Some do it for the money. Some are just mad or obsessed.

Back in my time at uni, volunteers had to be unpaid to ensure they do it kf their own free will. Its unclear which is better / worse.

[legolas2412]

A lot of people who take trips and meet friends and family (me included) instead of staying home, basically said that they will take the risk of being infected than losing part of life.

[nickpp]

For a nice sum, a whole bunch of people would probably volunteer.

[pgodzin]

An ethical consideration is whether it is ethical to disproportionately place the poorest (those most in need of a nice sum) at this unknown risk

[umeshunni]

Given that we have seen that the poorest are the most at risk of dying from the disease, I'm not sure that argument even holds any more. Sadly, it's this obsession with straw man arguments about ethics and equity that's cost the West a million lives in the last year.

[ls612]

I’m 25 and healthy. If they paid me $1000 and provided medical treatment if necessary I would have volunteered for such a trial last spring.

[tass]

Doesn’t this raise the same problem with the current manufacturing process?

There was limited capacity to manufacture back then, probably less so than there is today. Which vaccine candidate would Pfizer have manufactured? All of them?

[GavinB]

Yes, all of them. Or possibly expanding capacity for each of the major vaccine types, to be ready when we know which one is the winner.

And then, yes, a lot of those factories would have ended up sold for scrap (or mothballed for future pandemics or mutations). But the few that worked then save trillions of dollars of value and hundreds of thousands of lives.

It's a simple matter of calculating expected values and investing accordingly. But thats not how our civilization works.

[natechols]

Last year Bill Gates talked about doing exactly that (I don't know if this actually happened): https://www.businessinsider.com/bill-gates-factories-7-diffe... The fact that someone like Gates is throwing the idea around suggests that it's not really incompatible or inconsistent with our civilization. (EDIT: saw your other comment with the follow-up, sigh.)

[tass]

I'm going off the assumption that the capacity has been expanding as much as possible, so scrap factories wouldn't be a problem.

The Pfizer vaccine seems to have a shelf life of 6 months, so realistically the earliest they could have begun mass manufacture and have an effect today would have been June. That's right around the time they narrowed down to a single vaccine candidate.

I'm surprised that mass manufacturing didn't begin back then with the only possible candidate, especially since the US government also put their order in around that time. I can't find a whole lot of info on when they did ramp up (something I saw said October), and what reasons they had for not starting earlier.

[chuckcode]

Agree that relative to the cost in lives and global GDP leaders have drastically under invested in production and distribution of vaccines. Arguments about what ethical and incentive policies should be will continue forever. Certainly though we shouldn't be blocked at this point by availability of a few machines, shipping and inventory tracking, etc. Especially in the US we have really wasted 9-10 months to work on public health in general and vaccine delivery in particular. History will not be kind

[JoeAltmaier]

That's refuted in the article. We were not finished developing them in February. It took all the time it took, to find vaccines that actually worked. With science. Not throwing darts. Several companies have still not worked out their vaccines.

It's like saying "We had steel mills; we had cars back in February!" All it takes is designing and building them.

[Florin_Andrei]

> We did have it, we just didn't know which one it was.

What we had was the ending of Indiana Jones and the Last Crusade.

A table full of cups. Some of those have the Water of Life. Some just water. Some will outright kill you. Pick one.

It's only when you go through the trial process that you can separate the life-giving stuff from the rest.

[sna1l]

+1

It was clear the US government made the wrong decision when they backtracked and tried to buy more doses from Pfizer + Moderna[1]. Given how much the US has spent on stimulus, you would think even like 10-15 extra billion would be nothing.

[1]: https://www.nytimes.com/2020/12/07/us/trump-covid-vaccine-pf...

[gus_massa]

> And we refused to risk any individual life in order to potentially save hundreds of thousands or more.

Are you volunteering? Will you sign all the paperwork?

If you die in the trial or get a severe reaction, would your family be happy with the paperwork, or they will claim that they fooled you?

If you die and the vaccine candidate fails, will the TV claim that they should have used a good old method like a modified adenovirus instead of playing god and creating a frankenvirus in the lab?

[Symmetry]

I and a ton of other people signed up for challenge trials through 1 Day Sooner (https://www.1daysooner.org/). Sure, there was some risk to me but it was small compared to the potential to save the lives of older friends and family even before considering strangers.

[d7ryerh]

You make it sound as though no one would volunteer. I think you're severely underestimating the altruism of some people.

[ClumsyPilot]

People have voluntered for fucking one way trip to Mars. Maybe you think they are mad, but thats a different problem.

[visarga]

Instead of paying the volunteers they could give them free health care for the next 25 years or life. I bet many would take that chance.