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Comment by cameldrv | Hacker News Reader

I have to say, I cannot understand why the idea of doing a challenge trial is controversial. If you are using healthy, young, volunteers who are observed and have good access to medical care, how could it be unethical?

We allow people to donate a kidney to another person, and that carries a significant amount of risk, and only one person benefits.

We allow assisted suicide in many places.

We allow people to assume great risks in auto racing, professional football, and boxing, and that's just for entertainment.

We allow doctors to treat COVID patients, sometimes without even proper PPE, knowing that a significant number will catch it. Many doctors are also not young, not in good health, and have preexisting conditions.

So all of this is allowed, but when the potential result is a vaccine that could save millions of lives, somehow this is unethical?

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> I have to say, I cannot understand why the idea of doing a challenge trial is controversial. If you are using healthy, young, volunteers who are observed and have good access to medical care, how could it be unethical?

I think the most prelevant is COVID-19, at full strength, still kills seemingly healthy young people. The author mentions this in another article:

> The important question we have to consider is if it is ethical to deliberately expose even the young and healthy to the dangerous SARS-CoV-2 virus when we know it could seriously injure or kill them.[0]

In this article, we potentially have a weaker strains on our hands that could qualify as a fully ethical challenge trial that could accelerate the development.

At the end of the day, challenge trials are Phase trials with less restrictions in hopes of trading accuracy/rigor for speed.

Is it worth it? I don't know. I'm not knowledgeable enough to say one way or another.

[0] https://www.tillett.info/2020/04/24/it-is-unethical-to-not-s...

If you can use a weaker strain and presumably get the same results, of course, pick the safer option. However, if you can't, and people of sound mind are volunteering for noble reasons, why wouldn't we do that?

Is it worth it? We've lost about 200,000 people worldwide just in the past month from this disease. It's the leading cause of death in many countries. In healthy young people (20s, no preexisting conditions), the fatality rate is well under 0.1%.

If the vaccine doesn't work at all, which is unlikely, you'd expect 0-1 deaths from the trial. To save perhaps a single life of a willing, altruistic volunteer subject while hundreds of thousands die every month, and the world is confined to its homes is to me, utter insanity.

Do we tell firefighters to not go into a burning building to save lives, even if there is considerable risk?

If this is the state of medical ethics, the field should be torn down and rebuilt. To deny approval for a challenge trial with volunteers is mass murder.

Yes; but the explanation is unfortunately modern medical ethics is misnamed. The focus isn't on ethics, but on protecting the ethics board from accusations that they directly allowed someone to die or suffer.

The process is similar for most forms of regulation. The equilibrium is where no accident can be pinned on the regulators rather than on any sort of system-wide optimum. It can be very frustrating to deal with.

I've just learned in my thread above with the article author that there is no concept of exposing people post vaccination Phase II or III to see if it was effective. We normally wait a long time to see if people get sick. If it's effective them we go to mass rollout.

That's where the huge time savings is.

My previous statement of "it's a Phase trial with less restrictions" isn't true. It's making the feedback loop tighter.

With this new knowledge, I'm relatively convinced we should be doing a challenge trial to speed up the roll out.

There is a concept of using a challenge trial, only it can only be used when the risk to the volunteer is very low.

Challenge trial are used in trials on things like the common cold. SARS-CoV-2 is considered too dangerous to use in a challenge trial.

This is a great point. In order to get statistical significance, you need to subject the same number of people to the virus. In a non-challenge trial, we feel better about ourselves because the challenge is "natural", the subjects would have been exposed to it anyhow. In a challenge trial, you deliberately expose them. Either way, roughly the same number of people will be exposed to the virus.

Meanwhile, maybe 1,000,000 people a day are catching COVID. The bottleneck that stops that from continuing every single day involves some risk (if the vaccine doesn't work), of a few hundred people, who are in the most favorable position if they catch it, who volunteered.

"Better 1,000,000 people die from COVID than one person die that tried to stop it."

As a former medical researcher the underlying issue is that regulations only ratchet one way. There’s numerous ethics and oversight committees to please and rules put in place because of negligence or misconduct. There’s a line between human experimentation and research and they try to keep you far away from anything that could be interpreted as straddling it.

And there are very good reasons why historically as you allude to.

Me either, but it is considered so. Challenge trials can be considered ethical, but only when the risk to the volunteer is minimal.

Even if we (society) did decide that doing a challenge trial is worth the risk, we would be amiss to not look for a safer strain to use first. Only if we can’t find one after making a serious effort should we even think about using a dangerous strain.

I have to agree if there is full consent and extensive risk analysis. You wouldn’t step into a formula one car if you knew the wheels would fall off. You’d have to be convinced the team did everything to make the car the safest it could be.

And what if it is still a deathtrap that will kill 1% of people that step into it?

That's what makes it a good analogy. It's gotten safer in recent decades, but for most of its history the fatality rate of a career in Formula 1 was around 20%. It probably is on the order of 1% today (not every time you get in the car, but over a career).

I'm not sure why you're being downvoted; this seems like a legitimate question to me. Pasting a comment I made in another thread here:

> There are those that argue even without a safer strain it is ethical under certain circumstances to still perform that sort of "challenge trial" though, where people are deliberately exposed. A number of conditions would have to be met, such as all volunteer participation of course, very clear explanation and demonstration of understanding, no financial incentive, etc. But a faster vaccine could save many more lives than would be risked in the trial, and the risk itself could be very low, given the trial participants would be monitored closely and would get excellent medical care. Also obviously it would be restricted to young, healthy people without pre-existing conditions.

To me it seems like a solid argument that given all those conditions (and possibly others I haven't thought of or mentioned), such a trial should be allowed. My understanding is that there are many people preemptively volunteering to participate.

I'm not an ethicist, but I would be wary of the people "preemptively volunteering".

While the majority might have purely altruistic reasons, others could be dealing with mental illnesses that lead them to inappropriate action.

In the same way that there are older people saying things like "I'm willing to take my chances so that young people's jobs/lives/economy aren't destroyed" there are highly likely to be people offering to be guinea pigs for reasons that should ethically exclude them.

By lowering the risk to the absolute maximum level possible, as suggested by the OP, it could be possible to have a challenge trial within ethical boundaries.

This is more than "oh regulation is about CYA and that's what's holding us up", this is about "we don't kill or injure people in medical research, even if others might be saved."

Certainly it would be necessary to ensure people are of sound mind and understand the risk they're taking. That said, if we're talking about young, healthy people volunteering, and given they will be monitored throughout the trial, I would guess their risk of death would be on the order of 1/1000, if not better. (Based on recent estimates of overall CFR on the order of 0.5% out of NYC and such.)

That's not a risk I personally would want to take, but it's on the order of the risk people take when donating a kidney. (And of course for most people the process will be much less arduous than a kidney donation.) We consider that acceptable to save a single life, whereas a faster vaccine would save many. So my prior would be that most people volunteering for something like this are simply altruistic, similar to a kidney donor, rather than mentally ill.

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