Thanks for your thorough response. It is well-argued and as a result, I take back what I said. I’m not entirely convinced by your response but I will say I now have no idea! Being low-information on this, though, perhaps my reaction to the “challenge trial” idea mirrors other low-information responses, which is going to be most of them, so I’ll persist in explaining my thinking mainly in the hope it’ll help you and other pro-challenge people argue your case to others.
I’ll start with maybe my biggest worry about a challenge trial: the idea you could have a disease with an in-the-wild CFR of ~1%, that you could put 500 people through a challenge trial, and “very likely” none of them would die. With a CFR of 1%, expected fatalities among 500 people is 5. If medical observation and all the other precautions applied during a challenge trial reduces the CFR by a factor of 10, to 0.1%, your expected deaths is only 0.5, but that still seems unacceptably high for one trial, to me? To get the joint probability of zero deaths across all 500 people above 95%, you need closer to 0.01% CFR, (1−0.01%)500=0.951. Is it realistic to think all the precautions in a challenge trial can reduce CFR by a factor of 100 from 1% to 0.01%? I have no idea, perhaps you do, but I’d want to know before being feeling personally comfortable with a challenge trial.
Regaring R values and monkeypox generally, my understanding on this topic doesn’t go much beyond this post and the group of responses to it, so I’m pretty low-confidence on anything here. Thus, if you say the R is potentially quite high, I believe you.
Monkeypox virus is transmitted from one person to another by close contact with lesions, body fluids, respiratory droplets and contaminated materials such as bedding.
I’d have to guess it’s going to be less infectious than covid, which had an R around 5? On the other hand, since OP asked the question, there’s more speculation about chains of transmission that seem to indicate a higher R. I acknowledge “lower than 5” is a high error!
Having said that, to my mind, I now feel very conflicted. Having read AllAmericanBreakfast’s comment and their headline, I felt reassured that monkeypox wasn’t much for the public to be worried about, and the CDC and WHO would figure it out. But on my own understanding, if R is high (as you say) and CFR is anywhere much above 0.1%, and there’s a widespread outbreak, that is pretty scary and we should all be much more on the alert than we already are?
And that would affirm your conclusion that challenge trials would be a good idea, as long as we have confidence the risk to participants is low.
Thanks for your thorough response. It is well-argued and as a result, I take back what I said. I’m not entirely convinced by your response but I will say I now have no idea! Being low-information on this, though, perhaps my reaction to the “challenge trial” idea mirrors other low-information responses, which is going to be most of them, so I’ll persist in explaining my thinking mainly in the hope it’ll help you and other pro-challenge people argue your case to others.
I’ll start with maybe my biggest worry about a challenge trial: the idea you could have a disease with an in-the-wild CFR of ~1%, that you could put 500 people through a challenge trial, and “very likely” none of them would die. With a CFR of 1%, expected fatalities among 500 people is 5. If medical observation and all the other precautions applied during a challenge trial reduces the CFR by a factor of 10, to 0.1%, your expected deaths is only 0.5, but that still seems unacceptably high for one trial, to me? To get the joint probability of zero deaths across all 500 people above 95%, you need closer to 0.01% CFR, (1−0.01%)500=0.951. Is it realistic to think all the precautions in a challenge trial can reduce CFR by a factor of 100 from 1% to 0.01%? I have no idea, perhaps you do, but I’d want to know before being feeling personally comfortable with a challenge trial.
Regaring R values and monkeypox generally, my understanding on this topic doesn’t go much beyond this post and the group of responses to it, so I’m pretty low-confidence on anything here. Thus, if you say the R is potentially quite high, I believe you.
I do have additional uncertainty about R. From public reports about the means of transmission that [say](https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON385) things like
I’d have to guess it’s going to be less infectious than covid, which had an R around 5? On the other hand, since OP asked the question, there’s more speculation about chains of transmission that seem to indicate a higher R. I acknowledge “lower than 5” is a high error!
Having said that, to my mind, I now feel very conflicted. Having read AllAmericanBreakfast’s comment and their headline, I felt reassured that monkeypox wasn’t much for the public to be worried about, and the CDC and WHO would figure it out. But on my own understanding, if R is high (as you say) and CFR is anywhere much above 0.1%, and there’s a widespread outbreak, that is pretty scary and we should all be much more on the alert than we already are?
And that would affirm your conclusion that challenge trials would be a good idea, as long as we have confidence the risk to participants is low.