[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.

[Robotbeat]

Safety rules are good and valid. They are not a suicide pact, however. With a once-in-a-century global pandemic, brave volunteers should be allowed (through even earlier large-n phase 1 and 2 groups) to help expedite the safety approval of something that can save the lives of hundreds of thousands of Americans and millions of people worldwide.

[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.