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Comment by dcolkitt | Hacker News Reader

> The most reasonable approach is to assume that there is little to no durable protection from a single dose

How is that the most reasonable approach? Virtually every vaccine ever discovered provides more immunity on first dose, than the incremental gain on subsequent boosters.

You certainly can't be sure of this, but pre-existing evidence would strongly suggest that this vaccine is subject to the law of diminishing returns. At the end of the day, we're just trying to maximize infections prevented. If the two-dose schedule confers 95% immunity, then as long as we expect over 50% immunity from a single dose, then First Dose First is best policy.

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We have no data for mRNA vaccines except those trials. We don't know if the historical data on traditional vaccines are applicable here. As such, it is also possible that a single dose isn't good enough or a single dose is good enough but only for a couple months. We just don't know and it would be way worse if it turns out we have to re-vaccinate everyone because we were impatient.

> We have no data for mRNA vaccines except those trials. We don't know if the historical data on traditional vaccines are applicable here.

This is not how decision making under uncertainty works. When you don't have rigorous proof of whether something works or doesn't work you have to make educated guesses based on various priors and make the percentage play. You can't refuse to incorporate priors into your decision making just because you don't have a peer reviewed p<0.05 study validating it.

Uncertainty about the result cuts both ways. You can't claim that we can't do X over Y because we don't have rigorous proof that X is better than Y, when we don't have rigorous proof that Y is better than X either. Regardless of what you do you're taking a leap of faith.

> We just don't know and it would be way worse if it turns out we have to re-vaccinate everyone because we were impatient.

If there's probability p that it doesn't work and we have to spend X extra months re-vaccinating everyone that's an expected delay of p * X. But if it does work then not pursuing the single dose strategy will delay the vaccination schedule by X' months also.

If p * X < (1-p) * X' then the former is a perfectly acceptable risk.

I personally try to make decisions using probability. I understand where you are coming from but there is one factor missing in your analysis: this situation is literally life and death. That changes the math a bit to something more akin to "better safe than sorry" in my opinion. We have found a guaranteed path out of this mess. There may be other faster paths that save more lives, but it could also end up killing millions more too. I'm all for experimenting but I take issue with making the experiment the policy when lives are on the line.

We DO have a good understanding of the human immune system, and how the mRNA vaccines interact with it. The effectiveness shown in the trials confirm those theories.

Sure, there could be some odd unforeseen effect. If so we'd learn as we go.

> it would be way worse if it turns out we have to re-vaccinate everyone

Worse than 3000 people dying every day? Because of the extra expense of making more doses?

I know what you're getting at in this context, but in reality when you start digging into how the immune system works it's shocking how little is understood about it.

"There’s a joke about immunology, which Jessica Metcalf of Princeton recently told me. An immunologist and a cardiologist are kidnapped. The kidnappers threaten to shoot one of them, but promise to spare whoever has made the greater contribution to humanity.
The cardiologist says, “Well, I’ve identified drugs that have saved the lives of millions of people.” Impressed, the kidnappers turn to the immunologist. “What have you done?” they ask.
The immunologist says, “The thing is, the immune system is very complicated …”

And the cardiologist says, “Just shoot me now.”

From https://www.theatlantic.com/health/archive/2020/08/covid-19-... :)

heh.. :D

> We DO have a good understanding of the human immune system...

As someone who is an active researcher in this field, I can tell you that this is just not true. The immune system is VERY complex and we know very little about it. We have only had the tools to begin to systematically probe it for a few years.

Sure, there are plenty of bewildering mysteries in this field.

But I don't think they apply to these rather basic questions about how these mRNA vaccines work.

The theory for how they work is clear, and strongly confirmed by the studies showing 95% effectiveness.

Is there really any reason to think that a booster shot that provides 95% protection when given after 21 days will be damaging after 12 weeks?

Or that when two shots gives 95% immunity, 1 shot might give negative immunity?

This what's being implied by the "you never now, so let's do NOTHING" crowd here!

Propose to the companies to conduct a trial to test your hypothesis on the effectiveness of a single dose? Until then the FDA policy is clearly data based and they are saying to follow the tested dose schedule from the clinical trial and not to deviate.

Hypothetical question. Imagine if for some reason everyone in the trial received the vaccine on a rainy day (maybe it occured in Seattle during a bad patch of weather). The vaccine shows immunity, but we can only be sure for a population that got it on a rainy day.

Now we're distributing the vaccine, but the bottleneck is that we have to keep waiting for rainy days. It's especially bad in Arizona and Nevada. Is your contention that we keep the rainy day requirement? Even when all are scientific and empirical priors tell us that the effect is de minims.

The example is kind of silly, but it makes my point. There's literally countless number of factors that go into any trial. There's no possible way that the way treatment is deployed in the field will exactly match the way it was tested. Yet doctors, scientists and public health experts use judgement and empirical priors to determine when and where we can relax the requirements.

I think the analogy to your example is to have conducted a larger trial where the dose was given under different weather conditions, or in the case of the real vaccine vary the timing of the 2nd dose. I agree, if experts agree the likelihood that 1 dose is effective and the likelihood of it being ineffective is low, we should do what will save the most lives. This is an emergency.

" if experts agree the likelihood that 1 dose is effective and the likelihood of it being ineffective is low"

Experts do not agree.

> Yet doctors, scientists and public health experts use judgement and empirical priors to determine when and where we can relax the requirements.

They certainly do. And the FDA, a collection of the leading doctors, scientists, and public health experts, just told you that two doses is the regimen. Is there something that you know that these experts don't?

Considering that the FDA let thousands of Americans needlessly die because they delayed the approval hearing to enjoy a relaxing Thanksgiving weekend... Yes, I don’t trust their judgement.

As for more general critiques, there’s mountains of evidence that the FDA is too risk averse, even before Covid.

https://www.hoover.org/research/fdas-risky-risk-aversion

Setting aside my deep visceral reaction to what you're suggesting, how is it safe or productive to conduct a review on a Friday evening at the end of a long week and not sleep or eat until it is done? Do you have any reason to believe they would make more or fewer mistakes doing so? And what's your personal policy on making really important decisions while sleep deprived? Would you, for example, get some sleep before signing a contract on a house?

If anyone only ever made decisions while they were perfectly fed and rested, this would be a sad, slow, boring world, because nothing would ever get done or decided. There is such a thing as urgency, and people do work beyond a 35 hour work week with evenly spaced meals, and especially during a global pandemic.

Specific to this instance, this FDA meeting was a formality -- they had already had the data for two weeks to review. The efficacy was well-known. They chose to take a 4-day holiday (Thursday, Friday, Saturday, Sunday).

People don't all of a sudden sign house contracts. They've germinated the idea, spent weeks or months working through the pros and cons, talking to their life partners and family and agent and mortgage broker. The decision is made well in advance of the actual contract signing, and all the red lines are done before you get to the actual meeting to sign on the line. Similarly with the FDA regulators, they weren't meeting to review the data for the first time and come up with a decision on the spot. This was one final step in a very long process.

The application was submitted on November 22 and the review meeting was not scheduled until December 10. The UK, not exactly a country known for taking reckless medical risks, approved the Pfizer vaccine eight days earlier than the US despite receiving the application at the same time.

While nearly ten thousand Americans died, I guess the FDA was “catching up on its sleep”. Eight long days of glorious sleep!

And yet, regardless of your own personal feelings and beliefs, here we sit, locked in our little worlds which have been shrunk down to the space inside the walls of our homes, with a government mandated two dose regimen as you scream helplessly into the wind like an obese turtle on its back screeching for help. Because we're going to Follow the Science that the government and experts have decided is Correct. So stop complaining, stay the fuck inside, and quit questioning the science because you half-dosers are really starting to sound like antivaxxers and antimaskers all of a sudden.

A lot of ad hominem and hysterics, for someone who continuously dances around the very simple question. What is your prediction for the effectiveness of a single dose regime?

Because if it's over 50%, then the math is very simple. First doses must go first. Here's my simple proposal: I bet you $500 that the first peer-reviewed study to specifically test one-dose mRNA Covid-19 vaccines finds at least 50% effectiveness.

Talk is cheap, and I'm sure you get a lot of upvotes on Reddit and Twitter by sprouting some "Follow the Science" hashtag. But actual people's lives are on the line, so if you won't even risk a little bit of money on your beliefs, stop risking people's lives.

Your proposal is highly unspecified. I suggest that you should add a durability term or the 50% effectiveness is meaningless. That is, for how long do you suspect there to be at least 50% effectiveness?

Are you trolling? This is a comically slavish attitude towards "science," but sadly one that all too many people have.

Now replace "FDA" with "FAA" and "two doses is the regimen" with "the 737 MAX is safe."

737 MAX is a debacle all right, but FAA actually has a stellar track record as far as government agencies go, and is respected worldwide. Or replace FAA with NTSB.

There is nothing special with these two dose regimens. It's just what was decided to try for the first studies.

3-4 weeks are quite short intervals for booster shots, picked because of the urgency of getting results, not because it's optimal from a medical standpoint.

> FDA, a collection of the leading doctors, scientists, and public health experts

FDA is primarily a regulatory bureaucracy, tasked with enforcing federal law in this area. The incentives it is under do not always align with optimizing public health.

Are they "leading" because they lead in expertise or because they control the reigns of regulation?

I'm not sure I would describe the FDA as optimistically as you do - they are a collection of federal employees, leaning heavily on private industry expertise to navigate the demands of politicians, the expectations of the public, and needs of businesses.

It's not only about minimizing total infections. If it were, priority would be given based on social sphere sizes, eg priests and postmen before old people.

It's also about giving people a vaccine they can believe in, which allows them to return to some of their normal activities. If everyone is 50% safe, no one has any real expectation that they can take any risks without being infected. If half the people are 95% safe, that half can do more things (travel long distances, go to school) while the unvacccinated half can continue to avoid risks until more vaccine is available.

> It's not only about minimizing total infections. If it were, priority would be given based on social sphere sizes, eg priests and postmen before old people.

Exactly how it is rolled out here in Moscow. It has never occurred to me that it's not the one and obvious way.

But yes, the "Sputnik" vaccine has huge problems with giving people something they can believe in. Rolling it out in a "rational" order, as if they actually believe it works, is probably the most city government can do to raise confidence.

> How is that the most reasonable approach?

The reasonable approach is to be overly cautious. A false sense of security is worse than no security at all.

> A false sense of security is worse than no security at all.

True. But that isn't what is happening here.

This is more "some level of security which is less than absolute, and unclear what sense of security people will assume they have"

We've seen "false sense of security" arguments used time and time again to oppose partial, imperfect safety interventions (seat belts in cars is a great example).

The cautious thing to do is vaccinate the entire population with two doses. Oops, we don’t have enough doses for that.

Letting a couple hundred thousand people die because of a slow vaccination schedule is NOT the cautious approach.

It’s not just a question of 95% immunity vs. 50% immunity (even if we were to take your arbitrary 50% number at face value). It’s also a question of how long we expect the immunity to last for two-dose vs. one-dose, and where we expect to be in terms of virus spread and vaccine manufacturing and vaccination rates when that initial immunity runs out. These are complicated questions.

"Virtually every vaccine ever discovered provides more immunity on first dose, than the incremental gain on subsequent boosters."

Citation needed.

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