I agree with all points regarding actual risks which match my own actions and the recommendations I give friends and family.
The only point where my probability estimates seems to noticeable differs from yours is with HCQ:
11. Best scientific consensus ends up being that hydroxychloroquine was significantly effective: 20%
I sold to 15%, given studies are actively being halted let’s knock that down to 10% now.
I think it is still relatively likely that there are combinations of HCQ with esp. Zinc that might work. I have updated toward them not working by now but would still give them at least 40%. Pure HCQ obviously not. I would offer a bet between your 10% and my 40% i.e. 1 to 3 that in the end a treatment with HCQ plus other active ingredients turns out to be effective.
Disclaimer: I follow ScottAdamsSays on Twitter and while he is also uncertain the potential upsides seem to be huge. He mentions use as a prophylactic for personell at risk like medical and police. He pushes further looking into it and there are many posts about other countries using combinations of HCQ with Zinc and others. You mention Zinc yourself. It seems plausible that Zinc is the active ingredient and HCQ enables its uptake. I seem to remember that CellBioGuy also wrote something along these lines.
Happy to do a small wager at 25% odds if we have someone we both trust to hold the money, or you trust me to do so, up to $100 vs. $300, or we can do $1 vs. $3 symbolically with no trust issues. Judgment would be whatever Scott evaluates to in his prediction evaluation.
Note that I agree that it’s >10% that there is a worthwhile way to use HCQ as part of a treatment strategy. But that’s different from it being the scientific consensus!
For the disclaimer, I would be very, very wary updating from Scott Adams here. He can be insightful, but when he advocates for things that make the administration look good, he’d do that essentially irrespective of truth value. What you’re getting is “here’s the best case I could make given I already wrote the conclusion at the bottom of the page.” So if you do want to update off such things, you need to compare it to how good an argument you expected him to find!
@Zvi The deeper look by Glen below lets me update back to ~40% that HCQ as prophylactic i.e. taken before the infection works. I’m now willing to take my $10 vs. your $30. We would commit here and transfer by PayPal after Scott has resolved. OK?
All right, I accept the wager. Done. Your $10 vs. my $30, PayPal upon Scott’s resolution post. Since it’s been three days, you can back out any time between now and 6⁄22, if you update again or my note below wasn’t properly factored in.
Note that the bet is about what the “scientific consensus” is, rather than whether it actually works—if it works but there’s no consensus, I’d still win. I think a lot of the time, likely more than half the time, that HCQ would work if given correctly, the scientific consensus fails to acknowledge this.
11. Will the scientific consensus end up being that hydroxychloroquine was significantly effective?
UpToDate, the closest thing to a canonical medical recommendation site, currently says: “We suggest not using hydroxychloroquine or chloroquine in hospitalized patients given the lack of clear benefit and potential for toxicity. In June 2020, the US FDA revoked its emergency use authorization for these agents in patients with severe COVID-19, noting that the known and potential benefits no longer outweighed the known and potential risks”. False.
What surprised me most in this bet was how the significant number of studies that were started about HCQ—not only in the US—were basically all buried. None show any updates, not even negative results even long after their expected end dates.
Well, how else would we figure out if it actually works. We are not the experts.
Anyway. I take it. I have seen that it got banned by CDC and that would let me update a bit. But I want to move forward and the main motivator of having a bet is that I will follow it until next year :-)
Update: I expect to get in touch by DM here when results are due.
And Re Scott Adams: I know that he is pushing things. He is actually relatively transparent about that part esp. in his Periscopes. He is basically demoing most of his techniques for his audience (and his audience does a lot of the explaining in the replies). I don’t like him as he can be very offending/transgressing but it still possible to learn quite a bit about politics and psychology from him and he is always ahead of the curve.
So this covers use of HCQ plus Zinc as treatment and the people show the same symptoms (feaver, chills, headache,...; not only positive tests) than the controls.
This really leaves little room for any noticable benefits. I am updating toward lower than 10% now.
From the abstract: “The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%])”
So the treatment group did have a lower incidence of illness than the control group, but the difference wasn’t statistically significant. However, only 107 patients in total became ill. This is a rather small sample, so the results by no means rule out a clinically important benefit of HCQ. Even just taking the observed proportions as a best estimate, there’s a 17% reduction of illness in the treatment group, which doesn’t seem negligible, and the actual benefit could plausibly be considerably larger. (Of course, given the small sample size, it’s also plausible that the real effect is in the other direction.)
That study made me much more inclined to think HCQ is useful as a prophylactic.
Among the full study group there was a reduction of illness of a bit over 17% but it’s better than that: the study’s supplementary appendix includes a chart that breaks out various subgroups including a breakout by DAY. The most benefit was found for people who started treatment on day ONE post-exposure. Next best was starting on day TWO post-exposure. By day three there was a negligible benefit and by day four there was a negligible harm—that subgroup actually did a bit worse than the control group.
So to get an average 17% improvement across the whole group we’re combining two start days of positive improvement (days 1 and 2) with two start days that (eyeballing the chart) round off to roughly zero improvement (days 3 and 4). Since the N was pretty evenly spread across days, basic math says if we JUST looked at the benefit for people who start as early as day 1 or 2 we should expect to find about twice as much improvement which is to say a ~34% reduction in illness!
Given the curve on that data, I’m optimistic about prophylactic use; it’s possible that starting on day 0 or day −1 does even *better* than 34%. And (contrary to the retracted studies) they found no evidence at all of serious side effects or heart issues.
If this study result replicates then people who obtain HCQ in advance (so they don’t have to wait for study enrollment or shipping) and start taking it *immediately* upon known exposure are ~1/3rd less likely to show any symptoms of covid than if they didn’t do that. Which could save thousands of lives. (We can’t be 95% sure of this result yet because the study was too small, but less-than-perfect knowledge is still knowledge and under the current circumstances probably worth acting on.)
(Caveat: they didn’t find benefit for age>50, the group we care most about. Caveat to the caveat: there were only 5 people in the “control” for age 50 - they didn’t have nearly enough oldsters enrolled in the study to expect meaningful results for them.)
Thank you for looking deeper into this. A likely 1⁄3 reduction when taking it on day 1 is amazing. And if people at risk take it routinely (“day zero”) it might be even better. I guess I have to update back to 40% likely it works.
I agree with all points regarding actual risks which match my own actions and the recommendations I give friends and family.
The only point where my probability estimates seems to noticeable differs from yours is with HCQ:
I think it is still relatively likely that there are combinations of HCQ with esp. Zinc that might work. I have updated toward them not working by now but would still give them at least 40%. Pure HCQ obviously not. I would offer a bet between your 10% and my 40% i.e. 1 to 3 that in the end a treatment with HCQ plus other active ingredients turns out to be effective.
Disclaimer: I follow ScottAdamsSays on Twitter and while he is also uncertain the potential upsides seem to be huge. He mentions use as a prophylactic for personell at risk like medical and police. He pushes further looking into it and there are many posts about other countries using combinations of HCQ with Zinc and others. You mention Zinc yourself. It seems plausible that Zinc is the active ingredient and HCQ enables its uptake. I seem to remember that CellBioGuy also wrote something along these lines.
Happy to do a small wager at 25% odds if we have someone we both trust to hold the money, or you trust me to do so, up to $100 vs. $300, or we can do $1 vs. $3 symbolically with no trust issues. Judgment would be whatever Scott evaluates to in his prediction evaluation.
Note that I agree that it’s >10% that there is a worthwhile way to use HCQ as part of a treatment strategy. But that’s different from it being the scientific consensus!
For the disclaimer, I would be very, very wary updating from Scott Adams here. He can be insightful, but when he advocates for things that make the administration look good, he’d do that essentially irrespective of truth value. What you’re getting is “here’s the best case I could make given I already wrote the conclusion at the bottom of the page.” So if you do want to update off such things, you need to compare it to how good an argument you expected him to find!
@Zvi The deeper look by Glen below lets me update back to ~40% that HCQ as prophylactic i.e. taken before the infection works. I’m now willing to take my $10 vs. your $30. We would commit here and transfer by PayPal after Scott has resolved. OK?
All right, I accept the wager. Done. Your $10 vs. my $30, PayPal upon Scott’s resolution post. Since it’s been three days, you can back out any time between now and 6⁄22, if you update again or my note below wasn’t properly factored in.
Note that the bet is about what the “scientific consensus” is, rather than whether it actually works—if it works but there’s no consensus, I’d still win. I think a lot of the time, likely more than half the time, that HCQ would work if given correctly, the scientific consensus fails to acknowledge this.
Zvi won.
Scott:
https://astralcodexten.substack.com/p/mantic-monday-judging-april-covid
hurrah! betting ftw!
What surprised me most in this bet was how the significant number of studies that were started about HCQ—not only in the US—were basically all buried. None show any updates, not even negative results even long after their expected end dates.
Ongoing trials:
https://www.archbronconeumol.org/es-hydroxychloroquine-as-prophylaxis-for-coronavirus-avance-S0300289620301629
(I don’t know where else to post this; last post tagged Coronavirus is months old)
None of the HCQ studies listed on that page seem to have results even though at least some of them are past study completion date.
Well, how else would we figure out if it actually works. We are not the experts.
Anyway. I take it. I have seen that it got banned by CDC and that would let me update a bit. But I want to move forward and the main motivator of having a bet is that I will follow it until next year :-)
Update: I expect to get in touch by DM here when results are due.
And Re Scott Adams: I know that he is pushing things. He is actually relatively transparent about that part esp. in his Periscopes. He is basically demoing most of his techniques for his audience (and his audience does a lot of the explaining in the replies). I don’t like him as he can be very offending/transgressing but it still possible to learn quite a bit about politics and psychology from him and he is always ahead of the curve.
Thank you for offering the bet. I would have taken it. Unfortunately I see it just now that I have an update on the matter. See below.
Entirely fair. Nothing done, then.
Update: An RCT on HCQ as prophylactic is just out (with some evidence on Zinc too) and it is negative:
https://www.nejm.org/doi/full/10.1056/NEJMoa2016638
See also the supplementary material which has the details on Zinc:
https://www.nejm.org/doi/suppl/10.1056/NEJMoa2016638/suppl_file/nejmoa2016638_appendix.pdf
So this covers use of HCQ plus Zinc as treatment and the people show the same symptoms (feaver, chills, headache,...; not only positive tests) than the controls.
This really leaves little room for any noticable benefits. I am updating toward lower than 10% now.
From the abstract: “The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%])”
So the treatment group did have a lower incidence of illness than the control group, but the difference wasn’t statistically significant. However, only 107 patients in total became ill. This is a rather small sample, so the results by no means rule out a clinically important benefit of HCQ. Even just taking the observed proportions as a best estimate, there’s a 17% reduction of illness in the treatment group, which doesn’t seem negligible, and the actual benefit could plausibly be considerably larger. (Of course, given the small sample size, it’s also plausible that the real effect is in the other direction.)
That study made me much more inclined to think HCQ is useful as a prophylactic.
Among the full study group there was a reduction of illness of a bit over 17% but it’s better than that: the study’s supplementary appendix includes a chart that breaks out various subgroups including a breakout by DAY. The most benefit was found for people who started treatment on day ONE post-exposure. Next best was starting on day TWO post-exposure. By day three there was a negligible benefit and by day four there was a negligible harm—that subgroup actually did a bit worse than the control group.
So to get an average 17% improvement across the whole group we’re combining two start days of positive improvement (days 1 and 2) with two start days that (eyeballing the chart) round off to roughly zero improvement (days 3 and 4). Since the N was pretty evenly spread across days, basic math says if we JUST looked at the benefit for people who start as early as day 1 or 2 we should expect to find about twice as much improvement which is to say a ~34% reduction in illness!
Given the curve on that data, I’m optimistic about prophylactic use; it’s possible that starting on day 0 or day −1 does even *better* than 34%. And (contrary to the retracted studies) they found no evidence at all of serious side effects or heart issues.
If this study result replicates then people who obtain HCQ in advance (so they don’t have to wait for study enrollment or shipping) and start taking it *immediately* upon known exposure are ~1/3rd less likely to show any symptoms of covid than if they didn’t do that. Which could save thousands of lives. (We can’t be 95% sure of this result yet because the study was too small, but less-than-perfect knowledge is still knowledge and under the current circumstances probably worth acting on.)
(Caveat: they didn’t find benefit for age>50, the group we care most about. Caveat to the caveat: there were only 5 people in the “control” for age 50 - they didn’t have nearly enough oldsters enrolled in the study to expect meaningful results for them.)
Thank you for looking deeper into this. A likely 1⁄3 reduction when taking it on day 1 is amazing. And if people at risk take it routinely (“day zero”) it might be even better. I guess I have to update back to 40% likely it works.