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Comment by dragontamer | Hacker News Reader

The mRNA vaccines were completed within a week or two with modern technology. It took nearly a year to test: prove that it was safe, prove that it was effective (preventing deaths, preventing hospitalizations, preventing symptoms).

This blogpost completely ignores the difficult proof issue.

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We could have tested it in two weeks with paid volunteers.

The pay for brave vaccine testers could have literally been $1m and we’d have saved several trillion bucks and potentially over a million lives. Hell, make it $10m or $100m and you'd still save a ton of money.

We've done this for several other viruses: https://en.wikipedia.org/wiki/Human_challenge_study

We could test that it's safe, yes. Effective, no. You have to have the people out in the community, for both the vaccinated group and the control group, and then compare who gets infected in each group. The testing actually took less time than they expected due to the unfortunately-high prevalence of COVID-19 in the community.

No, the testers would be directly exposed as part of the trial, which is why they'd be compensated -- as opposed to waiting around for 9 months for some percent of people to be exposed.

And the control / placebo group?

You're really going to force testers to potentially pick up the placebo, and then inject them with COVID19 forcefully? I mean yeah, it'd work, but its generally considered immoral under today's philosophy of science.

Why wouldn't they be willing volunteers?

It would be quite possible for it to clearly be informed consent also, at least to the extent the disease was characterized at that point in time.

The reason people keep bringing it up is that the consequences of the pandemic have been much worse than the consequences of allowing a few thousand people to intentionally expose themselves to an infection in a controlled setting¹. It's not guaranteed that challenge trials would have mitigated the pandemic, but it's weird to just outright circumscribe the possibility when the ongoing downside is huge.

1. I use the odd phrasing here because lots of people pretty much choose to expose themselves to the infection anyway; maybe not explicitly, but close enough.

Would it be immoral if they were offered a million dollars?Honest question, because it feels like the philosophy might not match up with common experience. It feels like an interesting question. People voluntarily risk worse for less pay in other fields, e.g. the military.

And if it wasn't immoral, what is the dollar limit?

Money is worth different amounts to different people.

Bill Gates or Jeff Bezos will never risk their life for "only" a million bucks. Find a depressed + suicidal dude somewhere else, and they may be personally willing to risk their life for just $100.

Making an industry of people who are willing to harm themselves for money is... probably not the business we should be encouraging. And that's assuming everyone is "playing nice". At a minimum, it means that we'll be inclined to start experimenting upon the poor and depressed (and then shedding away moral qualms because they signed a piece of paper).

Historically speaking in the USA, we have legacies like the Tuskegee Syphilis Study, where African Americans were chosen as the control group and lied to about getting a Syphilis treatment: leading to a generation+ long distrust in science.

Yeah yeah, we can't "assume" scientists will be racist jackasses today. But... we still have to account for what happened in our history and why certain testing methodologies have become taboo.

Good points. It's obvious that the potential for ethical problems in such a situation is huge.

I've thought for similar questions that a required baseline would be to at least have a society that provides a viable minimum social safety net, as well as free healthcare. When external conditions compel people to risk their health for survival, it is impossible to ensure sound ethics.

The point about ensuring that science and scientists can be trusted in the future is also an excellent point.

Remember that in, say, a cancer treatment trial, patients are signing up to potentially not receive the treatment depending on the run-in and randomization phases. I'm not suggesting these patients are forced into that decision; rather, I'm just pointing that controlled, randomized trials have some ethical fuzziness around them.

But they already have cancer, and the treatment may (or may not) help them.

What's being proposed here is for people to sign up and then inject a potentially deadly disease into them.

But until treatments/vaccines were developed, everyone on Earth had the disease-equivalent, sometimes-fatal status of "no prior immunity to COVID".

Sure, the scale is massively different for a young healthy person: "susceptible to COVID" would mean a moderate chance of catching the disease (growing over time), and then a small chance of death or previous complications. But the "susceptibility" is also a "health condition" with nonzero risk-of-death.

And for society as a whole, COVID passed cancer as a cause of death last year, and in January 2021 has been killing about twice as many people as all cancers combined.

So "diagnosed-with-cancer" versus "susceptible-to-COVID" shouldn't be that different in terms of the kinds of risks we'd let informed people take to address that danger.

Not forcefully. He said paid volunteers. Why does the idea of challenge trials cause a furious reaction? Let's compare it to the space shuttle: 135 missions with 2 missions in which everyone died. That's a case fatality rate of 1.5% -- in the neighborhood of the Covid CFR. And I'd expect a challenge trial on young healthy volunteers to have a much lower CFR. Why is risking people for the shuttle OK, but risking people for a vaccine that benefits all of humanity not OK?

There's two big issues with this approach:

1) death is but only the worst outcome. Being on the space shuttle does bring risk, yes, but not a 50/50 chance of a significant impact to your general health.

2) you'll end up testing the vaccines largely on marginalized population and people with heavy financial problems, misrepresenting the population at large and showing biased result.

For this age range, the survival rate for everyone is 99.98%. It'd be even higher if your screened aggressively for comorbidities / general health and provided everyone with top notch healthcare knowing in advance they have been exposed.

I would sign up for this in a heartbeat. Not only for the cash payment -- but you'd be a local hero and you could feel good for the rest of your life about taking a small risk to save the lives of many ill or elderly people.

So 2 person out of 10 000 dies. You would be a local hero and you would probably feel good for the rest of your life which is 2 weeks time. Also, let’s talk about long COVID. Nobody knows how long is it stay with you or if you even recover from it. You are a hero but you cannot climb the stairs anymore. And you will be forgotten in months.

Except the point is people were willing to sign up knowing that is exactly the risk they're undertaking.

The alternative that we chose was hundreds of thousands of more deaths and millions of more cases. From people who didn't sign up for it.

[1 Day Sooner](https://www.1daysooner.org/) is an organisation pushing for these trials, that's found 38,000 informed volunteers who would be willing to do these trials. Force is completely unnecessary, there are enough altruistic people who are willing to do trials like this

Total ethical failure here. You are supposed to not make people ill.

2,000,000+ people are dead because we didn't take this path.

The risk to testers under 40 would have been negligible. I'm not being flippant about other peoples' lives -- I would have signed up myself if the compensation was high enough.

> The risk to testers under 40 would have been negligible.

Luke Letlow (age 41) says otherwise, since he's dead. Okay, he's above 40, but he's high-profile and easy for me to remember. Plenty of sub 40 year olds have died.

Even among the survivors... plenty of young and healthy 20-30 year olds are having month-long recoveries, unable to breath at their old capacity.

Purposefully damaging the control group (who by definition, must NOT receive the vaccine) is immoral. Whether people in the control group believe in the potential harms of the disease or not.

"One person died" isn't a refutation, it's just an appeal to emotion.

Under 40 the survival rate is 99.98% for everyone -- including the already ill. If you screened for comorbidities and gave people great healthcare, you could get that 99.999% or higher. And save millions of lives (and trillions of dollars) by doing so.

> Under 40 the survival rate is 99.98% for everyone -- including the already ill

I doubt that. But I'm not entirely sure how to calculate the numbers you just said.

https://www.cdc.gov/nchs/nvss/vsrr/covid_weekly/index.htm

I realize this page changes, so I've taken a screenshot here: https://imgur.com/0iM5FHC

This is the chart of who died in January 2021. Yes, most deaths are aged 65+, but there's been deaths in all age categories. I doubt its 99.98% as you suggest (especially since the current case-mortality-rate is ~2.5%, at least for my state)

The official CDC numbers are stratified from 35 to 44, I'm not entirely sure who you are citing to get "below 40" age groups.

It lists the total population for each age group. Just the 35 to 44 age group is above 99.98% (given the death counts in younger age groups it's obviously still true if you include them in the calculation):

(1-7057/41659144)*100=99.983%

I expect the individual probability of surviving infection is not that high for each member of the group though. It's not clear if that meaning is intended anywhere above.

> 41659144

That's the total population of all 35 to 44 year olds in all of the USA.

> 99.983%

That's 0.02% of all 35 to 44 year olds have died, including those who never had COVID. IN ONE MONTH, not including the people who died two months ago, or 3 months ago.

"from 1/1/2020 to 1/30/2021"

It's for the entire period of the pandemic.

You are correct in pointing out that it isn't looking at deaths/infection.

I do appreciate the correction by the way.

Why is it immoral to allow people to take a risk that they explicitly consent to (ensuring they have full knowledge of the potential consequences), but not immoral to let hundreds of thousands or millions more people die that you could have potentially saved if you undertook the challenge trials?

A few bad cases and deaths that were consented to, versus hundreds of thousands to millions of cases and deaths from people that didn't consent. This morality scale doesn't make sense.

Disregarding a way to accelerate vaccine development by months, and save literally hundreds of thousands of lives along the way, because one thoughtlessly applies cliches like "you are supposed to not make people ill", even though the people who you make ill are all volunteers, well aware of the risk, and handsomely compensated for it, is the real total ethical failure.

It's as if when there are some "professional" ethicists in the area who give "professional" ethical guidance, people lose their natural moral sense, and defer to their "professional" guidance no matter how silly it is if you apply even modicum of scrutiny.

In order to use this method to test a vaccine for deployment to people over 65, you need people over 65 in your control group.

This means you are choosing people to murder.

A ridiculous exaggeration; you’re asking for volunteers to take a risk. Not killing them.

People can decide for themselves to take risks. You may not agree with the choices they make and that is your problem. Not theirs.

No, I am saying that volunteer challenge trials don't test what want to test so their results are useless at best, and murder at worst.

Do separate branches then. Use challenge trials to accelerate deployment to under 30s (or whatever) and natural infection for other age brackets.

I honestly haven't thought deeply about the ethics, but it's really concerning that it has become such a hard rule that preventing people from injuring themselves in a particular way (we don't prevent lots of other forms of injury) is somehow obviously superior to letting tens of thousands of people die for lack of information.

The vaccine is going to be deployed to communities at risk first, you can't test vulnerable populations via volunteer challenge trials.

That's circular. If the challenge trial is successful, start deploying it to the groups tested using that method and then shift to the at risk groups as data justifies it.

It won't hurt the at risk groups to start up high volume manufacturing earlier (it will likely help them), and there is a benefit to everyone each time anyone is vaccinated (the reduction in transmission efficiency).

Or, do the standard vaccine safety and efficacy testing, deploy the vaccine to the people who need it most first, and save more lives.

Optimizing deployment of the virus to bored 20 year olds may be popular among bored 20 year olds, but it isn't the best public health strategy.

There is no reason to expect a challenge trial would slow down the standard branch of the trial. If it gave an earlier result, the differences would be good ones! The production would have worked through initial scaling and a bunch of people would be vaccinated.

Do you think the vaccines being distributed right now were manufactured more than a few weeks ago or something?

Maybe, or you developed and scaled up production of a vaccine that only worked on young healthy adults who don't need it that much, and kills or maims everyone else. Wasting a ton of time, resources, and good will that could have been better spent saving lives instead of getting 20 year olds back to bars.

Remember it wasn't a given that mRNA vaccines were going to work, we were lucky.

It's hindsight, but none of the SARS-CoV-2 vaccines in use have that problem, nor do several more that are likely to be approved for emergency use.

What proportion of approved vaccines in general have such radically different responses in different age groups or demographics?

I don't think that's true. You still need to study the testers over a period of time. With a human challenge study you can get by with fewer testers and a little less time, but it won't be that different.

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