It’s a tangent from the thread, I suppose, but one of the things that has struck me throughout all this is how we have at least seemed to make scant use of human challenge trials. If that’s really out of (somewhat indefensible, if you as me) ethical concerns and nothing else, then the pandemic is simply not as threatening as we make it out to be. One can’t have it both ways. Or at least not in my mind. The way we’ve had it seems to be full of little more than dressed-up (and often glorified) guess work, which might have been fine for a while, since we might have stumbled upon some answers, but by now seems little more than negligent.
What answers do you think human challenge trials would have provided that the current studies haven’t? 
We could test other booster shot windows a lot quicker. We could test how infectious vaccinated people are a lot quicker.
At this point challenge trials would be a complete non-starter, at least under US scientific study rules. We know COVID-19 is dangerous for some people, even young healthy people. The problem is we don’t know which young healthy people it will be dangerous to.
Besides, with massive amounts of community spread, it isn’t necessary to do challenge trials to get data. That’s one of the reasons the vaccine trials completed so quickly. The control groups hit the necessary number of cases very quickly. Lack of community spread was one of the major factors that stopped development of a SARS-COV-1 vaccine.
For any scientific study, the chance of harm to the person being tested must be weighed against the benefit to the person being tested. The harm of being infected with COVID-19 is very real, and potentially very serious for even young healthy people. Most will be fine, but a non-trivial percentages of them will not be fine. The exact numbers aren’t well characterized, but are definitely far too high to risk deliberately infecting people when the benefit to that person is zero.
Remember, this is how real science and medicine works. It takes time. This is not a problem that will be solved in act 3, or even in a two part episode.
Well, then do we know all we need to know yet, or don’t we? Did we get all the information we need of those vaccine trials, or didn’t we? My impression has been that we didn’t. My initial reply was to this:
So many caveats, so much ‘we don’t know know yet’.
And if this is true:
then how it is also true that there is no use for challenge trials that provide better data in less time?
Because, as I explained, it would be unethical to run challenge trials. The trials would be high risk for the participants, with no benefit to the individual participants. It doesn’t matter if it would provide better data.
For something like a voluntary trial, the amount of risk young healthy people have from COVID-19 is considered high risk. Paying people to participate is not considered a benefit, but rather coercion. The payment can’t be high enough to cause people to do something outside of their own best interest.
The numbers are almost spot on. And individual over 65 has a 33 x chance of dying than does a 40 year old.
I’m not sure about that. People perform other tasks with high personal risk. Since the US is loosing billions per day we could start with 1,000 people being paid 1,000,000 each. Or say we need 1,000 people and auction it off like the airlines do when they are overbooked, and give everyone the amount offered the last taker. Or offer death row inmates commuted sentences.
What are you not sure of? That people could be convinced to participate in a challenge trial, or that it’s ethical to hold one, because other people do risky things?
As I said, offering $1,000,000 to somebody to participate in a challenge trial would be considered coercion, and it would never pass an institutional review board.
Prisoners are considered a special class in scientific studies, because they are wards of the state. Even asking them to participate in a scientific study can potentially be considered coercion, because the people asking have tremendous power over the inmates. People I work with have had to do all kinds of things to get IRB approval to even interview people in prison, let alone do something that may cause them permanent harm.
Deaths due to skydiving appear to be about 0.5-1 per 100,000 jumps. Motor vehicle deaths are about 1.25 per 100 million vehicle miles. Infection fatality rate for COVID-19 in people 20-40 appear to be 0.01-0.50, depending on sources. I’m not sure exactly how to compare those things.
Will people do risky things for fun? Yes. Will people do risky things if you offer them lots of money? Yes. Will people do risky things if you hold a lethal injection to their arm and offer a way out? Yes. Are any of those scenarios going to pass an IRB? Absolutely not.
Will people do a risky thing if it offers them a great deal of non-coercive benefit? Yes, and that might pass an IRB. “This experimental medication may turn your hair green, but it is also likely to cure your chronic hiccups.”
I agree with you about challenge trials, but I think pointing out that these suggestions won’t pass an IRB is missing our opponents’ point, as they are arguing that we should let these ethical concerns go in a crisis:
I’m aware of that. I’m responding from the perspective of somebody doing human subject research in an academic setting.
The challenge trial proponents have a similar argument to what was being made 9 months ago about untested vaccines, hydroxychloroquine, and other untested treatments. “Things are too dire to see if this works, we need to do something, and this is something, so let’s do it.” Now it is “ethics aren’t a luxury we have time for.”
How many people can we sacrifice for the greater good? Trolley problem. What if we could just convince people to not play on the tracks by wearing a mask and avoiding unnecessary gatherings?
That sounds entirely reasonable, so I expect a large subset of the population to vehemently opposed that.
It also sounds entirely naive to me. For all the bitching and moaning about how this thing would be over if only people would wear masks, it seems to me that the great, great majority of people, in the great majority of places, are wearing masks. It’s not working. Whatever we’re trying is not working. So maybe it’s time to try something new.
Or, again, maybe it’s just not so big a crisis after all. I am aware of a volunteer human challenge trial movement afoot, though I don’t know how much traction it is getting. But the fact that the mere notion is dismissed out of hand, out of concern for the safety of the miniscule proportion of the population who would be impacted by it, is a pretty good gauge on where things stand.
For what it’s worth, one writer’s take on it:
What source gives 0.50 ?
…can you be specific on what it is you think “isn’t working?”
You’re right; it’s not as threatening as it’s often made out to be. People talk about it as if it’s the Black Plague, and it’s not even remotely close to that level.
Your point?
Probably something from early in the pandemic out of Europe, as IFR estimates have mostly gone down over time. I was trying to find something of the current best guess IFR, but I didn’t see anything exactly on point, so I didn’t save my searches.
Here is one from the New York outbreak last spring, which estimates IFR for under 25 at 0.01%, but for 25-44 at 0.116%. It is within an order of magnitude of 0.5.
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30769-6/fulltext
No matter how you look at it though, COVID-19 is still a risky disease for young adults. For instance in this study, 2.7% of those 18-34 hospitalized for COVID-19 died. As the study says, that is twice the rate of death for the same age group hospitalized with acute myocardial infarction. That is just a death outcome, which is not the only bad outcome. A much larger percentage of that group will suffer long term.
What I wasn’t able to find was a good indication of the percentage of young adults who end up hospitalized.
I think people get distracted by the much larger danger to older people, which minimizes the risk to young people. According to CDC numbers, since 1/1/2020 more than 3% of the deaths of those 25-34 were due to COVID. That means COVID accounts for somewhat more deaths than liver disease (2.1%) and about half due to heart disease (7.3%) in that age range.
So to wind that back to the original point, should we do heart attack challenge studies in young people? Heart disease is responsible for 1/3 of the deaths (pre-COVID) of those over 65. Even when hospitalized, only a small fraction of young people who had a heart attack will die.
Here’s the CDC’s best estimates of IFR by age:
0-19 years: 0.003%
20-49 years: 0.02%
50-69 years: 0.5%
70+ years: 5.4%
More granular data from O’Driscoll et al., 2020 published in Nature:
0-4 years: 0.003%
5-9 years: 0.001%
10-14 years: 0.001%
15-19 years: 0.003%
20-24 years: 0.006%
25-29 years: 0.013%
30-34 years: 0.024%
35-39 years: 0.04%
40-44 years: 0.075%
45-49 years: 0.121%
50-54 years: 0.207%
55-59 years: 0.323%
60-64 years: 0.456%
65-69 years: 1.075%
70-74 years: 1.674%
75-79 years: 3.203%
80+ years: 8.292%
My point is that the cognitive dissonance is deafening. We can’t do human challenge trials because the risk is just too great to make it worth it, but at the same time we can’t gather two families without killing grandma, or however you want to frame it. It’s like, which is it? Really, which is it?