"I'm not 100% sure why Strongyloides emerged as the top contender"
From quick noodling around because it's often prevalent in a lot of places, prevalence is unrecognised, it causes a bunch of symptoms that can be mistaken for other things, and medical professionals don't tend to test for it regularly so are unaware if a patient is suffering from an infestation.
You've got "stupidity" in the sense of a bad world model that produces random conclusions, but then you've also got "stupidity" in the sense that smart people have looked at an idea and think it's dumb. The first one isn't anti-correlated with reality, but the second one definitely is- and there are things that can selectively bias people in favor of that sort of thing. For example, when experts and credible sources disproportionately belong to a political class that you oppose, when you rely for your livelihood on the attention that comes from being contrarian, when you're enamored by the narrative of being a lone voice of truth in a world of illusions, and so on.
Alex Jones ticks enough of those boxes that him taking a stand on a controversial issue is pretty decent evidence that experts take the opposite stand- which is pretty decent evidence that his position is false.
Also, suppose you've already seen some evidence for and against a position, and have a lot of uncertainty about whether it's true. If you unexpectedly discover that there's a prolific and very dumb counter-culture promoting one side of the issue, shouldn't you wonder whether the evidence you've seen was biased by that group's efforts and adjust your credence accordingly? Reversed stupidity may not be intelligence for a blank slate, but if there's any chance you've been influenced by stupid, reversing it by a proportional amount just seems prudent.
"They're turning the frogs gay!" isn't a theory that environmental endocrine disruptors are affecting sexual development in amphibian populations. It's a theory that the US government is using chemical warfare as a form of population control by feminizing men and turning them gay to stop procreation. One of the side effects of this plot is that now most frogs are homosexuals. Suffice it to say, Alex Jones is wrong about this.
Alex Jones was using a bit of pop coverage about a known scientific phenomenon, distorting it, and folding it into a ludicrous conspiracy theory. Being suspicious of Alex Jones endorsed conspiracies doesn't require you to dispute every single detail found in them, however strained.
I don't know. How many? I suspect not a lot. I'm not sure the answer is greater than zero. The causality is oddly inverted here as Jones's conspiracy theories trade on popular media coverage of scientific findings.
What we have is a Scott Alexander anecdote where Scott brings up in polite company that what Alex Jones was talking bout was actually real and feels admonished for this. There's not much we can make of that, though it is notable that what Alex Jones was talking about wasn't real if you actually understand what his whole rant about the frogs being turned gay is about, so there's that.
If you assumed that what Alex Jones says must be wrong, then you'd assume he was wrong about them turning the frogs gay (whether it's a side-effect or regardless of intentionality).
Do you think the person was asserting that if Alex Jones believe it is a good idea to breath air, then Alex Jones must be wrong? I think we're able to give credit to how people colloquially communicate ideas and presume they probably mean that Alex Jones is apt to be on the wrong side of issues controversial issues that aren't conventionally accepted among people with greater credibility. That's usually what people mean when they express something like this.
If the response is, "But he wasn't wrong about the gay frog thing!," then I think it is worth noting that he was, in fact, wrong about that, both in the particulars of the assertion and what theory he was trying to communicate with that. That he loosely based it on a widely covered phenomenon that isn't all that controversial misses the point.
Yes, but let's face it: This is some noise-ass, low-veracity Bayesian evidence, to be fair, and probably shouldn't budge your needle much in one direction or the other.
If you know someone to be a pathological liar, disbelieving everything they say that you can't independently verify is not only a good bet, I would argue it's your ethical duty.
The key here is that there has to be another "side" in the argument that the pathological liar is diametrically opposed to. If propositions imply that one is false and one is true, you can make safe inferences on the other position based on which side the liar is on.
Obviously most issues aren't that clean, but as a heuristic, it could be a lot worse.
The Nazis were well known for lying. And when they found a bunch of bodies in the Katyn forest and blamed it on the Soviets, the natural assumption would be the Nazis were blaming one of their own numerous massacres on another "side". But they were actually telling the truth in that instance, and your heuristic would repeatedly fail if you assumed the opposite side of a known liar must be a truthteller. It's entirely feasible for two liars to be opposed to each other.
That's the other obvious failure mode of this heuristic, yes. But the majority of people are not outright liars, especially in the scientific community, so it's still useful in this instance and many others. (Also, it should go without saying that no individual failure of a heuristic makes it invalid; the existence of solar eclipses does not make the "dark outside -> it's night time" heuristic useless.)
This was during the southeast Delta death surge…ivermectin as prescribed in Florida is clearly ineffective:
A recent study examining trends in ivermectin dispensing from outpatient retail pharmacies in the United States during the COVID-19 pandemic showed an increase from an average of 3,600 prescriptions per week at the pre-pandemic baseline (March 16, 2019–March 13, 2020) to a peak of 39,000 prescriptions in the week ending on January 8, 2021.1 Since early July 2021, outpatient ivermectin dispensing has again begun to rapidly increase, reaching more than 88,000 prescriptions in the week ending August 13, 2021. This represents a 24-fold increase from the pre-pandemic baseline. (Figure)
Unfortunately patient self advocacy is like playing chutes and ladders. Encounter a medical problem for you or your loved one and find out- there's no hand holding
That's literally the same as arguing that eating sugar is bad because Hitler ate sugar. So if Alex Jones said that eating healthy is good then all reasonable people should go eat only fries at McDonalds 3 times a day 7 days a week?
This is a false equivalence, because Alex Jones believes lots of true things he doesn't put on his show. What he chooses to put on his show is filtered for controversy and sensationalism. Nothing he puts on his show will be anything people generally agree is true.
Well if you want to believe everything that people generally agree is true then you can just do that and cut out the Alex Jones involvement.
Believing everything that people generally agree is true is a pretty good strategy in life. You'll be right more often than you're wrong, and when you're wrong then at least you don't lose too many friends over it.
But if you're happy to just follow the believe-what-everyone-else-believes strategy then you needn't waste your time reading rationalist-adjacent blogs like this, which are about the often-quixotic struggle to do ever so slightly better than the general consensus.
Well, I don't think that it's quite this simple these days, as compared to say 70 years ago. To an extent, there are now two mainstreams, the "establishment" and "anti-establishment" ones, to vaguely gesture at their essence. Many reasonable people believe that certain prevalent and high-status expert endorsed narratives are thoroughly wrong or "not even wrong". Arguably, Alex Jones serves a useful role in trawling through the "anti-establishment" thought-space and gathering all of its worst trash in one place. I wonder if there's an "establishment" equivalent.
70 years ago there was also an establishment and an anti-establishment. The anti-establishment included Civil Rights activists, draft-resisters, folk/rock musicians, etc. And, admittedly, lots of wackos.
I think the point is that Alex Jones generally airs the opposite of what people generally agree on, so it's still valuable information, thus you shouldn't cut out people like him. If you want to go for "believe everything people generally agree on", it's a lot less effort to watch AJones and believe the opposite, than to go around and ask everyone about what they believe on those same issues.
It's not bad as a first approximation. But to then go on and say that a first approximation is all you need and no one should do further analysis, is stupid.
Jones is, in fact, right sometimes, even when he says controversial things. And some things he's wrong about have decent evidence for them.
Whether a drug has massive value against Covid is certainly a question worth more than a rough heuristic.
A sensitive instrument is one that can pick up and amplify small signals that others miss, and no doubt this "sensitivity" has been an integral part of what has made your writing as successful as it has been. Getting overwhelmed more easily than you might otherwise be is the other side of that tradeoff, and it's great that you're not letting the tough side of that get in the way of giving things the response you know they're due.
Thanks for taking the time to respond to him, even though it hasn't been fun. I doubt I'm the only one that notices and appreciates the effort.
> Dr. Ioannidis is known to be unusually rigorous and this is part of his pro-rigor crusade
I'm not familiar with all his work, but I think he deserves a reputation for self-promotion more than a reputation for rigor. I think his most famous essay is "Why Most Published Research Findings Are False", and I think this paper is notable for its sensational headline much more than for its careful analysis.
The early seroprevalence study had quite a few serious problems - but even worse he used it to generalize from non-representative sampling to wrongly characterize the virulence of COVID by a wide margin.
It's too perfect that this response to Ioannidis was co-authored by someone (Sander Greenland) who had positive things to say about Alexandros' analysis on Andrew Gelman's blog.
I didn't really have an opinion on Ioannidis before COVID times. But during the pandemic, I got a quite poor impression of him.
He was one of the early figures to warn that COVID might be an overrated problem, especially that mortality might be lower than common estimates, and gave his own, much lower estimates, of the problem. Even then I had the impression that his data looked rather cherry-picked. He dismissed some of the best and cleanest sources from that time, from cruising ships and from Bergamo and other European regions, which would have been more alarming. That data was cleaner than what he took. But this was during the first few weeks of the pandemic, in a chaotic situation, and no data was really good, so that was still kind of ok.
But the real problem was that he didn't update when better studies came out. A year later, he would still stick to his old estimates in public interviews, even though there were much better studies by then, and his estimates were far out of the plausible range. Honestly, it was getting ridiculous.
I know that he deserves big praise for uncovering the replication crisis, but I really think that his performance during COVID was a scientific and Bayesian failure. Perhaps he became hyper-skeptical of studies after the replication crisis (or was so before, which made him detect it). But the issue is that he didn't just concluded "We don't know", but that he concluded "We don't know, so don't take the estimates from the literature, but take my own even more fishy estimates instead." And sticked with that.
Wow, thanks for sharing! I didn't know that it was so bad.
It's sad that such a brilliant mind can be trapped in some believe and totally disconnect from evidence about it. There are quite a few tragic cases like this, like physicist Roger Penrose or mathematician Michael Atiyah. Ioannidis is not there yet, but he might be heading that way.
I didn't really follow what Ioannides did, he isn't a public figure here in Europe. For example, I didn't know about his attacks on the PhD student.
But I noticed some bits, especially in March 2020, and later sporadically when he gave interviews to the news here, and my impression is pretty consistent with the article. It's just that the article contains a lot more of the same stuff.
I was rather thinking of his concept of consciousness. He started with the idea that consciousness can impossibly be restricted by Gödel's incompleteness theorem, and thus computers can never become conscious. In more elaborate versions he insists that consciousness is impossible without resorting to quantum gravity effects in the brain. All this is completely detached from any evidence (in fact, there is lots of evidence against it) except for his gut feeling of what properties consciousness should have.
I think the Penrose and Atiyah cases are somewhat different.
Penrose started going publicly off the rails about Consciousness And All That with "The Emperor's New Mind", published in 1989 when he was 58 and still (so far as I can tell) a genuinely brilliant mind.
Atiyah started going off the rails in his late 80s, when he was fairly clearly losing his mind. This wasn't a matter of a brilliant mathematician/physicist getting taken in by a bad idea, it was a matter of a _formerly_ brilliant mathematician/physicist no longer being able to tell good ideas from bad ones. A very different kind of tragedy.
"He dismissed some of the best and cleanest sources from that time, from cruising ships and from Bergamo and other European regions"
This has probably been argued elsewhere, but cruise ship passengers tend to be older and fatter than the general population. Italy also has a lot of old people.
The sources may be clean from the point of view that the populations are isolated, but they aren't representative in other ways.
True, and these things need to be accounted for. But this is possible and should be done, and the data should not be completely thrown out of the window. In the Bergamo region with about 1,000,000 people, the number of deaths in March 2020 was six times as high as in a normal month. So this March had half as many deaths as otherwise a whole year! Of course, this can become a bit less worse at other places if you adjust for age.
But Ioannidis arrived at the prediction:
"If we had not known about a new virus out there, and had not checked individuals with PCR tests, the number of total deaths due to “influenza-like illness” would not seem unusual this year. At most, we might have casually noted that flu this season seems to be a bit worse than average. The media coverage would have been less than for an NBA game between the two most indifferent teams."
Granted, this was mid-March 2020, but at this time preliminary death numbers from (smaller) parts of Bergamo were already available. There was just no way to arrive at his conclusion by "adjusting for age". Still, if he had corrected his estimates one or two months later, that would have been fine. But he sticked to them (and actively propagated them) long after the point where they were simply ridiculous.
The general population isn't the primary comparison due to age. The cruise ship data WERE controlled by age - but they didn't control for factors like SES - which I think would likely make cruise passengers HEALTHIER (more active, better baseline health, more access to care, etc.) than their age-matched peers
As such, I was shocked when, early on in the pandemic, he extrapolated a generalized IFR from the Santa Clara seroprevalence study without any post stratification for such factors as SES or race/ethnicity. It's a fundamental mistake of science to extrapolate from non-representative sampling in that way. Here's a good interrogation of the poor epidemiological science in that study (from an UCSF Grand Rounds talk):
And that's on top of the ethical violations in that study (recruitment telling people they'd get an "immunity passport" if they tested positive without telling them of false positives - at least one co-author quit the study over that) and other dubious aspects like recruiting through personal emails from the wife of one of the authors. And that's all on top of the questionable statistical methodology:
Based on that fundamentally flawed science he went on a national TV campaign where he significantly underestimated the virulence of COVID - likening it to the seasonal flu.
OK, everyone made mistakes with COVID - but the fundamental scientific flaws underlying the mechanisms of his errors were shockingly bad for an epidemiologist of his stature.
And then he has the gall to complain about the politicization of the science during the pandemic - which of course IS a HUGE problem but he contributed significantly to that problem.
I'm repeating this comment because it appeared to get truncated above? (I'm not familiar with this comment interface)
I had been quite a fan of Ioannidis.
As such, I was shocked when, early on in the pandemic, he extrapolated a generalized IFR from the Santa Clara seroprevalence study without any post stratification for such factors as SES or race/ethnicity. It's a fundamental mistake of science to extrapolate from non-representative sampling in that way. Here's a good interrogation of the poor epidemiological science in that study (from an UCSF Grand Rounds talk):
And that's on top of the ethical violations in that study (recruitment telling people they'd get an "immunity passport" if they tested positive without telling them of false positives - at least one co-author quit the study over that) and other dubious aspects like recruiting through personal emails from the wife of one of the authors. And that's all on top of the questionable statistical methodology:
Based on that fundamentally flawed science he went on a national TV campaign where he significantly underestimated the virulence of COVID - likening it to the seasonal flu.
OK, everyone made mistakes with COVID - but the fundamental scientific flaws underlying the mechanisms of his errors were shockingly bad for an epidemiologist of his stature.
And then he has the gall to complain about the politicization of the science during the pandemic - which of course IS a HUGE problem but he contributed significantly to that problem.
We have done an intensive study of viral load dynamics in our phase 2 platform trial. Ivermectin got dropped pretty quickly (pre-specified futility rule was met). In contrast, known effective antivirals such as casirivimab/imdevimab and remdesivir showed an effect on viral load dynamics pretty quickly.
Alexandros blocked me on Twitter long ago just for repeatedly asking whether there was one good RCT supporting ivermectin. He apparently runs a startup, yet has the time to write a series of posts that literally total over 86,000 words (a sizeable non-fiction book!) just to respond to ONE blog post from Scott. And he did this over the space of a few months.
In other words, he has been engaged in a 24/7 side hustle--writing a full non-fiction book in a few months -- and moreover, it was all on a very narrow question about whether one particular blogger was mean about a particular drug that supposedly is a miracle cure for Covid (even though no rigorous study has ever shown that). Odd choice of priorities.
And despite aiming towards rationality, he is keen to write thousands of words nitpicking at the tiniest flaws in any negative ivermectin study, even while defending much worse studies or websites that defend ivermectin. Blatant double standard.
PS, when I spent 5 minutes pasting Alexandros' blog posts into Microsoft Word, the result is 291 pages long (single spaced). Even if someone was unemployed, who has the energy for that kind of monomania?
I'd agree. But given the double standard (which you repeatedly and correctly note), he is not "trying to get things right." He's trying to defend ivermectin at all costs -- he comes up with the smallest nitpicks at any study showing that ivermectin doesn't work, while defending much lower-quality pro-ivermectin studies on the grounds that "but there's a STAT article" or "but this guy won a science competition" or some similarly one-sided argument.
Okay, so what we're generally implying when we accuse somebody of having 'double standards' is that they're deliberately misinterpreting data. But when you're dealing with this much data, and a discourse that spans months, asymmetries in your application of epistemic rigor are bound to emerge.
In my submission, this doesn't really confirm a deliberate misinterpretation of the data. Scott does a reasonably good job being generous about that here.
Yeah, especially since many here, including me, are prone to doing exactly that. And besides, I'm not sure it's a bad trait. It makes life harder for the person who has it, but it probably also makes them likelier to obsessively try to get something right, and succeed at doing so.
To be clear, it's not bad to obsess over getting something right. But I think it's to obsess over defending a predetermined position at all costs (have you read my friend Julia Galef's book on the scout mindset?)
Scott, I admire you for following through on writing this. My guess is that holding yourself to your pledged sucked, but you did it because you'd said you would, and also because you felt bad about some errors of yours Alexandros had pointed out. Jeez, write something you enjoy the hell out of next.
I absolutely hate this kind of thing. Alexandros can invest his time however he likes. And blocking people for repeatedly tweeting the same thing at you is generally reasonable behavior.
Yes, he can indeed invest his time in eminently ridiculous ways. Up to him. But it is still subject to ridicule by other people who are interested in what's actually true. If he were actually interested in truth, he wouldn't have such a double standard that accepts and defends the fringe-iest evidence for ivermectin while ridiculing and often blocking anyone who asks for more rigorous evidence.
I expect Scott put way more time into writing this response than he wanted to. In fact my guess is that working on it SUCKED, and that he held himself to doing so anyway because he said he would, and also because he felt bad about so genuine mistakes that Alexandros pointed out. Want to make fun of Scott's obsessiveness too?
"If he were actually interested in truth, he wouldn't have such a double standard that accepts and defends the fringe-iest evidence for ivermectin while ridiculing and often blocking anyone who asks for more rigorous evidence."
Also, the thing none of us know about Alexandros is why he's persisting. Is he so invested in being Ivermectin Man that he can't allow himself to see how bad the case for it is? (That's my theory.) Does he know so little about research he can't tell good from bad? Does he know the evidence for Ivermectin's terrible, but he's cynically pretending it is not because he's profiting from being an advocate for the drug? But you're not addressing that question -- just throwing rotten eggs at him.
Could be any or all of the above, but the thing is that even by you, there is no reasonable explanation. All of them are bad for Alexandros. So why are you so eager to keep weighing in on behalf of someone for whom there is no possible rational defense?
Because I think that laughing at someone who's been bested is meanspirited. If the mockery is mixed with new information or a new take on what happens, then I experience it differently -- then it's an angry, substantive comment.
But we don't have to pretend that everyone is trying to get at the truth. Alexandros is applying an absurd double standard whereby any negative ivermectin study has to be scrutinized for every tiny flaw whereas pro-ivermectin studies will be excused for far greater flaws.
There is plenty of room for good faith people to engage in discussions without always being derailed by the impulse to give the benefit of the doubt to people who don't deserve it.
Look, I'm no fan of Alexandros but I don't think you really score any points against him here. Why would he block you on Twitter for repeatedly asking whether there is one good RCT supporting Ivermectin? He thinks there are multiple good RCT's, doesn't he? Seems more likely that he pointed to studies that he considered good RCT's, you said, "no they're not because . . ." and he got tired of arguing with you.
Why does writing a full non-fiction book while running a start-up suggest that he or the contents of his book are not to be trusted? Maybe he's got lots of energy -- or maybe he's bad at time management -- or maybe he's just overinvested in winning the argument with Scott, even though the practical consequences of his winning or losing are small. All these possible personal failing of his seems kind of irrelevant in the context of a discussion of whether he's right about ivermectin, or whether he's arguing in good faith.
As for his nitpicking flaws in studies that don't support Ivermectin's efficacy, and his defending bad studies that do -- well, he would say that the flaws he's picking aren't nits, they're big, and the studies he's defending are not bad. I think he probably believes that.
If you had multiple exchanges with him, there's no way I'm going to dig through the manure pile of Twitter for them. I did read the exchange you linked, and it's not clear what his view is about good RCT's existing. He once says "no good RCT's" but I don't know what he means -- is it agreement? a sarcastic gibe? If he really thought there were none, I'd expect him to say something like, "yes, OK, all the studies are imperfect, still if you look at the mass of evidence blah blah. . ." Then later he says something like "nothing would convince you." That could mean he's pointed to what he thinks are good RCT's and you dismiss them as not, or I suppose it could mean something else. So this exchange with Alexandros is far from solid evidence that he doesn't believe there are good RCTs. Actually, it's sort of like the case for Ivermectin's efficacy -- you can point to it as evidence for your view, but in fact it's full of holes.
Look, I hope it's clear that I do not think Ivermectin is useful against covid. I just don't like the way you're making fun of Alexandros. I get that he annoys the hell out of you, but if you want to go after him make good points, don't just snigger,
No, he never pointed to even one good RCT. Earlier in the discussion, he pointed to ivmmeta.com (not a trustworthy website) and the Bryant meta-analysis (also not reliable because it included fraudulent studies). That's all he had.
But say, why are you trying to reconstruct Twitter history from 2021 to critique me on the grounds that Alexandros MIGHT have said something defensible back then? Why do you care so much, such that you're inventing alternative histories in which he had good RCTs to cite (which he didn't)? Why bend over backwards to give every possible benefit of the doubt to him rather than to me?
"As for his nitpicking flaws in studies that don't support Ivermectin's efficacy, and his defending bad studies that do -- well, he would say that the flaws he's picking aren't nits, they're big, and the studies he's defending are not bad. "
If he thinks that, he doesn't know what he's talking about, because it is objectively wrong. For example, the TOGETHER trial is not objectively worse than the Borody study -- quite the contrary.
Hey, I agree that the case for Ivermectin is bad and the case against it is good. It's just not clear what point you're making about Alexandros by saying he's very critical of good studies and goes easy on bad ones. We're all aware of the thing you keep pointing to -- yep, ridiculously hypercritical of studies that weight against Ivermectin. And?
To give the other side of this thing, his company has produced this: <https://www.balena.io/etcher>, which is a really nice way to flash USBs and which has saved me a bunch of time in the past.
Well, no. He's writing on a controversial topic that inspires fervent support amongst true believers. His comments show he's clearly attracted an audience, and he's baited Scott, who has a huge audience, into writing a long post in response. So whatever else he has done, his efforts have won him a big audience that he can than parlay into either a platform for his ideas or into some kind of monetary profit. You are being rather uncharitable to assume he did all over an obsessive need to prove Scott wrong.
Scott's original post had so much stuff in it that if it was on any other subject we would have called it a Gish Gallop. It's unsurprising that responding to everything in it would take such a huge number of words.
I don't think that's fair. The characteristic of a Gish gallop is that one throws out a large number of basically-independent claims without providing justification for any of them, taking advantage of the facts that (1) one can _state_ something much more quickly than _refuting_ it and (2) if you merely state something and someone else merely denies it, then to most people it looks as if you're in the right and they're in the wrong.
Scott's ivermectin post wasn't like that. It's mostly long because it's looking at a large number of studies, which ivmmeta can simply list in a big table but Scott had to look at in at least a paragraph's worth of detail.
Scott's post was the _exact opposite_ of a Gish gallop: it was very long because it was responding to something else that was long but didn't go into details.
(Maybe you could argue that he should have looked in _more_ detail at some of the studies. That would almost certainly have made his post longer, not shorter.)
The important trait here is not how much detail it has, but that it has many arguments that would take a lot of time and space to respond to--so much that most people would give up because of the volume, regardless of whether the arguments have merit.
Complaining about Alexandros using a huge number of words to respond to Scott isn't fair; Scott said so much that in order to respond fully, he *had* to use a huge number of words.
I agree that complaining about the length of AM's response to SA is likely unreasonable. (It depends on what that length actually consists of; I haven't looked myself.)
What I'm objecting to is something more specific: "if it was on any other subject we would have called it a Gish gallop". I hope we wouldn't, because "Gish gallop" doesn't just mean "very long thing", it means a particular _kind_ of very long thing, and Scott's post was unambiguously not that kind of very long thing.
This analysis is great but I'd like to pay more attention to what our prior should be that some existing medication has a substantial benefit in treating a new disease when there isn't a strong theoretical basis supporting that use. My sense is that our prior should be very low. I mean, just ask yourself how much you'd be willing to bet about a large rigorous study showing a 10% drop in deaths from a random drug.
All the argument as to what direction the studies on ivermectin point is great and all, but even in the best case the evidence isn't very strong. I mean, it's not unusual in the slightest in medicine to see some initially suggestive studies only for the effect to turn out to be a mirage.
So while I think pinning down just how much evidence we have for ivermectin is important insofar as it should inform us whether to bother investing in yet more studies the idea that this should be enough to convince you to take the bet against the strongly theoretically supported side-effects (plus a reasonable prior that many drugs have them) seems like a big stretch.
I agree. On the other hand, one thing Ivermectin has going for it is that it's cheap, easily accessible (and probably quick to make) and well-tolerated. And there weren't many other drugs that were: fluvoxamine and metformin were the only ones I heard about (and actually I don't know whether metformin is cheap or well-tolerated) .It would have been a great thing for the world if some drug like Ivermectin that did give some survival benefit, even a small one, had been discovered. The drug we finally came up with, Paxlovid, is highly effective for unvaccinated people, but it took a long time to develop, is not cheap, not easily accessible, and so unpleasant to take that many people bail before finishing the full course of medication. So I can see giving things like Ivermectin the benefit of the doubt in early research -- though I agree that the pro-Ivermectin people kept going long after it was time to give up.
"and actually I don't know whether metformin is cheap or well-tolerated"
Reasonably so, there are generics of it available. Well-tolerated - the worst side effects are gastrointestinal and usually calm down in a couple of days (though some people get it worse and can't stay on it).
I've been taking metformin for several years now for Type II diabetes and it didn't stop me contracting Covid. Anecdotes are not data, but that is my lived experience 😁
If it does anything it's not prevention of illness, it's improving outcomes. A number of studies found it reduces chance of ER visits and hospitalization, but some did not. Pros and cons are easy to find via google. Current official US guidelines are to not prescribe it for people with covid. A couple of the docs on medical Twitter whom I respect think that's a bad recommendation because metformin's way better than nothing. It's certainly not as helpful as Paxlovid, but Paxlovid's expensive and soon a lot of poor folks in the US will not have insurance that will allow them to get Paxlovid. Metformin was also available when Covid began. Paxlovid was ready to use about a year later, but the supply was limited for a while so it was 18 mos. until it was available for all. And of course Metformin could be used in parts of the world where nobody gets Paxlovid. Here are a couple of studies with positive findings:
"Who knows, maybe it reduced your illness severity."
Hard to say, I had a murderous cough (so bad that once I nearly fainted from coughing so hard and not being able to catch my breath). Another family member had no cough but constant vomiting to the point of becoming severely dehydrated (couldn't even keep water down, anything they consumed came right back up). Two other family members just breezed through it like a bad cold.
Especialy when it come to viral disease. There are very, very few effective antiviral drugs, and those that do exist and work are usually the results of a very long trail of arduous and expensive research.
The reason is completely obvious: bacteria have their own biochemistry, thousands of chemical reactions unique to them, which human cells do not use, and which are potential targets for chemical warfare. That's why there are tons of antiobiotics, and lots of compounds, both natural and artificial, show anti-bacterial properties. Viruses don't have any biochemistry at all, because they're not alive. They have *no* chemical reactions unique to them. An effective antiviral needs to interfere delicately but effectively in the chemistry of the invaded human cell, so that it blocks viral entry or reproduction -- which is carried out by human cell reactions -- but doesn't do bad things to the cell.
It's a miracle this is even possible at all, so delicate is the balance to be struck. So the baseline assumption about suggestions that any drug or herbal supplement or whatever is effective that *isn't* the result of some brain-straining enormous expensive effort should be skepticism bordering on incredulity.
But drugs can help in other ways besides being antivirals My understanding is that metformin's mode of action (assuming it really does help covid patients) doesn't involve blocking viral entry or reproduction, but instead mitigating some of the effects downstream from that, eg cytokine storms. This article talks about that: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154087/
Of course such drugs are much harder to find -- seems almost a matter of luck. If you're looking for a covid antiviral you can just throw a drug in with some pseudovirus and see how well the drug blocks the virus. There's no simple way to find out which of the many drugs in use that do not qualify as antivirals slow down the processes by which covid does a lot of damage in those who are infected. In fact I have no idea how metformin was identified as possibly helpful. Nobody seems to be touting it as an antiviral.
Sure. Supportive care is still all we've got in many cases, but it rarely changes outcomes in the kind of miraculous reversal way that you get with antibiotics and bubonic plague, say. It can't, because it's not getting at the root of the problem. I mean...if some people are going to go into full tinfoil-hat frenzy because Big Medicine is pooh-poohing folk remedy X that reduces the severity of symptoms or duration of disease by 15% it's just more of the shouting at the clouds that makes me think watching birds in the feeder in my backyard is a more productive use of my time than the Internet.
But who's going into full tinfoil hat frenzy over this? Since I'm the only person in this discussion speaking up in favor of metformin & similar, it does feel a bit like you're talking about my view. I hope it's clear that I'm not even sure metformin works -- some think if does not. My point, made before you entered the discussion, was that having some cheap, widely available, well-tolerated drug would have made a lot of difference early on in the pandemic (which was when some, including Scott, were talking about fluvoxamine and metformin as a possible drug of that type). Something that at present does nothing more for a covid sufferer than shorten the illness a bit would have made a lot more difference than that early in the pandemic, when few people had immunity, there was no vax and there were no antivirals. And of course in some parts of the world there is still is little or no vax and no antivirals.
And the study I linked to did find considerably more benefit than a 15% redux in symptoms or duration. There was a substantial difference in death rate between metformin users and nonusers.
I must admit that I scrolled straight to the conclusions, and even that felt like a strain at this stage of the ivermectin conversation. The graph of likely false positive results at the end of the post was quite interesting, and I admire Scott's dedication to this topic. Otherwise, I'm hoping we can all move on to other topics!
I guess that Scott wrote this in large part because there's a bigger and always relevant meta-topic of what to belive in the absence of "settled science", and how easy it is to make the mistake of thinking that you've gleaned a valuable insight from the messy landscape.
You seem to be missing the positive results in the MedinCell trial and the new paper on hemagglutination showing that IVM both prevents and reverses RBC clotting associated with poor outcomes.
This was primarily about the studies we discussed in 2021, with me only mentioning a few especially large and well-done studies since then. Still, those seem interesting - can you give me links to those studies?
Yeah, Bret Weinstein did a video on those results recently. I thought Scott's original article was a net win for Team Ivermectin in any case- even being right for the wrong reasons makes a case for having a public debate.
That MedinCell trial also seems very fishy on its face. It randomized 399 people to ivermectin or placebo, and measured how many got infected with Covid in 28 days. https://www.medincell.com/wp-content/uploads/2023/01/PR-results-TTG-VF-EN.pdf In the placebo group, they claim that 105 out of 199 people got a Covid infection in 28 days. Really? Unless this was a challenge trial, it is hard to imagine that over half of people came down with Covid in a 4-week period.
I'd totally believe those numbers if they'd come from, say, China last December.
MedinCell says they did the study in Bulgaria "between March and November 2022"; I don't know about infection rates there, so off the top of my head I'd say it's questionable but not totally unbelievable.
I agree with these conclusions a lot more than those from your original post.
One quibble: what does "clinically significant effects" mean? Is the burden "better than a placebo"? "Better than Paxlovid"? "Better than no placebo"? The differences in efficacy between those thresholds are large enough to drive a truck through.
I originally framed it as d > 0.3, but as mentioned in the quote in 7B, Alexandros preferred to talk about a 10%+ drop in mortality for high-risk patients.
I think there might be a typo in the phrase "not for excess mortality in the control group" in the Cadegiani et al section
If they were hypothetically going to condemn him for giving unhelpful drugs to people, wouldn't that involve them complaining about excess mortality in the treatment group, not the control group?
Outside of the technical arguments, you deserve credit for taking the high road in responding to Alexandros.
If nothing else, his bad faith characterizations of you made it clear that he's not very strictly bound by the available evidence. No one is perfectly in control all the time, especially when there's strong disagreement - but getting as far out over his skis as he did in impugning your motivations is a strong tell for "motivated reasoning." Unless he's got mind-reading skills which he hasn't yet explicated.
But the bottom line is that accountability is the key - and you've demonstrated accountability here.
I don't think he was especially bad faith. I accused him of being bad in a few ways, he accused me of being bad in a few ways, we mostly disagree with each other, but this seems within the normal range.
Maybe - but normal range is a pretty low standard, imo.
I'm not going to go back and look and I could be wrong, but my recollection was that there was a difference in that he explicitly attributed conscious mal-intent and impugned your motivations in ways that required mind-probing, whereas you (perhaps foolishly) observed on sub-optimal behavior.
I see a distinction there as the one set of actions is unnecessary and counterproductive, whereas the other reflects fallacious (or motivated) reasoning.
That might seem like semantics but as an observer, for me it reflects a meaningful category difference. Of course, we can and do all cross that line at times; the question then becomes about frequency and more importantly accountability.
On accountability, I recall trying to engage with him on the fallaciousness of his process of attributing motivation and intent on your part, and him being totally unaccountable/unreflective
It would be interesting to go back and see if my characterization of my exchange with him isn't correct, as that would reveal a form of bias on my part. But it would be take too long a time to find it.
I think not so much Alexandros as his fanboys, who kept popping up here to pester Scott about "why haven't you answered Alexandros yet, huh? huh? have you read this new study, huh? huh? why won't you admit you were wrong and he was right, huh? huh?"
I doubt Ivermectin works, happy to be convinced with stronger evidence.
What I found most alarming was how politicized Ivermectin became, most glaringly with the CDC, pretending as if Ivermectin was only for livestock with their infamous "you are not a horse" tweet [1] which may (?) have encouraged people like Dr Jason McElyea to make up fictitious stories about people "clogging up hospital beds because they are OD'ing on Ivermectin" [2]
Meanwhile, the CDC suggests ivermectin off-label to treat lice, even though there are plenty of FDA approved OTC and prescription treatments [3]. I quote:
"Given as a tablet in mass drug administrations, oral ivermectin has been used extensively and safely for over two decades in many countries to treat filarial worm infections. Although not FDA-approved for the treatment of lice, ivermectin tablets given in a single oral dose of 200 micrograms/kg or 400 micrograms/kg repeated in 9-10 days has been shown effective against head lice"
I think it should probably have been made available over the counter, instead of being heavily suppressed. At the very least that wouldn't have fed the fire of conspiracy theories as much, and it's probably safer for people who want to take it not to have to rely on veterinary or questionable sources.
I’ve always leaned towards explaining Ivermectin’s apparent success in the developing world as a case of a low-resource medical team throwing everything they got free from WHO at a novel infection, which then got written up as, “My 20yo cousin got broad-spectrum antivirals AND Ivermectin and lived….my 80yo uncle only got the antivirals and died…must have been the Ivermectin,” with a small side order of parasite load.
A lot of the stories in 2020 were of the, “We really don’t know much…here’s a handful of straws to clutch at…” variety.
Exactly. With the survival rate between 99 and 99.9 for people under 50, it's difficult to separate placebo from cure without large scale double blind RCT, then replicate those RCTs.
What was so sad the last 3 years was how political ideology dictated which were the favorable placebos, which allowed absolutely terrible studies to get praised. Case in point, consider "Lifting Universal Masking in Schools — Covid-19 Incidence among Students and Staff" which somehow made it into NEJM to promote cloth masking toddlers.
I think part of the problem also was the various 'miracle cures' were being peddled alongside "don't get vaccinated, take this instead" like Dr. Cadegiani and his co-authors:
Lucy Kerris is a paid consultant for both Vitamedic, an ivermectin manufacturer, and is co-founder, as well as acting as a paid consultant, for Médicos Pela Vida (MPV), an organization that promotes ivermectin as a treatment for COVID-19 and discourages COVID-19 vaccination.
Flavio A. Cadegiani was a paid consultant (USD 1,600.00) for Vitamedic, an ivermectin manufacturer. Dr. Cadegiani is a founding member of the Front Line COVID-19 Critical Care Alliance (FLCCC), an organization that promotes ivermectin as a treatment for COVID-19.
Pierre Kory is the President and Chief Medical Officer of the Front Line COVID-19 Critical Care Alliance (FLCCC), an organization that promotes ivermectin as a treatment for COVID-19 and discourages COVID-19 vaccination. Dr. Kory reports receiving payments from FLCCC. In February of 2022, Dr. Kory opened a private telehealth fee-based service to evaluate and treat patients with acute COVID, long-haul COVID, and post-vaccination syndromes. Dr. Kory expresses personal points of view against COVID-19 vaccination.
Jennifer A. Hibberd is a co-founder of the Canadian Covid Care Alliance and World Council for Health, both of which discourage vaccination and encourage ivermectin as a treatment for COVID-19.
Juan J. Chamie-Quintero is a contributor to the Front Line COVID-19 Critical Care Alliance (FLCCC), lists the FLCCC as his employer on his LinkedIn page, and expresses personal points of view against COVID-19 vaccination."
So whatever the virtues of ivermectin (which remain to be proven re: covid), the publicising of it as a cure was being done with a side of "vaccines bad, don't trust Big Pharma, don't trust the authorities!" which is not going to make the authorities trying to grapple with a new pandemic trust your take or look favourably on your miracle cure, hence the "it's horse paste".
Especially if people were going on Youtube with 'hacks' about "if your doctor won't prescribe it for you, buy it off veterinary stores" which is risky enough - maybe ivermectin won't do you harm, but in general don't take animal medicines, stick with human formulations. For animals (rat studies in this case, but warnings for dogs as well on another site):
"Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality."
Okay, that's overdosing, but someone taking medications made for (yes) horses might indeed overdose as well.
The ones who work for ivermectin manufacturers do seem suspect, but aren't you (ahem) putting the cart before the horse on the FLCCC (and similar) people?
They *formed* these organizations in response to their impressions that ivermectin was super-helpful in treating Covid, and in opposition to people promoting vaccines *because they thought ivermectin works*.
While they may be factually wrong in this, if they were correct then agitating for ivermectin and making it easier for people to get would be morally admirable, if not imperative.
I don't know much about most of these people, but Kory in particular is a long-time ICU doctor with a pretty impressive research background -- I can't see how the grift would be worth the squeeze for somebody like that.
Considering the sums of Money big pharma slings around that 1600$ consulting fee sounds laughable. Especially considering the risk a lot of these people took going against the FDA/CDC and a lot of the mainstream. If they are financially motivated they are pretty stupid about it.
I think many engineers would quibble with the characterization of Elon Musk as an engineer, let alone a brilliant one. He does seem to have had a knack for a) picking investments in engineering companies to buy* or start, and b) hiring good engineers to work for him. But those are not engineering.
* One of his main mistakes with Twitter seems to be his belief that it's an engineering company, rather than a media company.
I'm not sure where I saw it, maybe I can dig it up, but I saw a pretty good round up for sources that basically all said "No, Elon really was the head engineer - or at least one of the top ones - at SpaceX."
I'm not a huge Musk fan, but I think a lot of people are overcorrecting wrt to his competence.
I would like to see those sources. Musk has no formal engineering education, and from what I've seen so far, he shows no appreciation of how absurd (or at least absurdly difficult) many of the things he promises are. The vibe I'm getting is much more "this sounds good, let's sell it and let my dudes figure out how to implement it" than "I have a genius solution to a really hard problem, here is why we can do what no one else can".
FWIW, before he was such a public figure, I read a lot of people claiming first-hand knowledge that he's a brilliant engineer and was indeed responsible for a lot of rocket science at SpaceX. I have no sources or whatever, so take it for what it's worth.
I'm not surprised it's at odds with what you've heard, lots of people in media love to hate on Musk, probably because Musk comes across as self-important and self-aggrandizing in many ways. I think only time will tell for sure.
My mental model of the guy isn't some charismatic business guy who "LARPs as an engineer", (to borrow eleventhkeys terminology), but that he's actually more of a dubiously charismatic engineer who ended up running large businesses, and frankly has a certain amount of distain and disinterest in the business side of things.
This is at least part of the impression I got from him when he came on Dan Carlin's Hardcore History Addendum feed last year - he doesn't come across as particularly charismatic but spends a lot of the time "nerding out" about the technical details of WWII fighter jets.
I don't deny there's certain some level of intentional hype-building in his process, but it's hard for me to judge how much, and overall his track record on technical stuff seems pretty good? (SpaceX, EVs, and Starlink all seem like fairly clear 'wins') Maybe I'm just not familiar with some of the 'absurd promises' he's made? (He's definitely proven over-optimistic about self-driving timeline)
My mental model is that he's a brilliant manipulator and neither a good engineer nor a good businessman per se, but very good at pretending to be both - good enough to fail upward far enough that it becomes difficult to doubt his capabilities.
Regarding the absurd promises, here are a few:
- the Hyperloop
- the Loop (digging lots of tunnels for battery-powered pods to "solve traffic")
- rockets for passenger transportation between cities
- a battery-powered hypersonic jet
- Mars colonies any time within the next decade
That stuff is so transparently daft and Sci-Fi-y, it makes my head burst with cognitive dissonance.
Quote (I've broken it into chunks and slightly cleaned up, but there's ~no interpunction):
i think in many corners he does not get the respect that he should about being a wealthy person that could just retire and he went all in where he was really going to.
you know he could have gone bust and there's plenty of people you look at the you know the sad uh athletes or entertainers that had all the money in the world and blew it he could have been the business case example of that
but the things that he was doing space exploration electrification of transportation uh solar city type things these are big world level things and i have a great deal of admiration that he was willing to throw himself so completely into that
because in contrast with myself i was doing armadillo aerospace with this tightly bounded... it was john's crazy money at the time that had a finite limit on it. it was never going to impact me or my family if it completely failed and i was still hedging my bets working at id software at the time when he had been you know really all in there
i have a huge amount of respect for that and people do not
the other thing i get irritated with is people that say it's like oh elon's just just a business guy you know he just was gifted the money and he's just kind of uh investing in all of this
when he was really deeply involved in a lot of the decisions you know not all of them were perfect but i know he cared very much about engine material selection propellant selection and for years he'd be kind of telling me things like "get off that hydrogen peroxide stuff, liquid oxygen is the, it's the only proper oxidizer for this
like the times that i've gone through the factories with him we're we're talking very detailed things about how this weld is made how this sub assembly goes together, what are like startup shutdown behaviors of the different things
so he is really in there at a very detailed level and i think that he is the best modern example now of someone that tries to that can effectively micromanage some decisions on things on both tesla you know and spacex to some degree where he cares enough about it
i worry a lot that he is stretched too thin; you get boring company and neuralink and twitter and all the other possible things there where i know i've got i i've got limits on how much i can pay attention to
i have to kind of box off different amounts of time and i look back at my aerospace side of things it's like i did not go all in on that i did not commit myself at a level that it would have taken to be successful
I'm pretty sure I saw the same list of sources praising Musk, and it was almost exclusively people that currently worked for him. I can't imagine any of Musk's employees being allowed to say "Oh sure, my billionaire boss is actually kind of useless as an engineer".
I think Musk is an exceptional CEO, who for some reason wants to be known, instead, as a genius inventor and engineer. He's a great businessman who wants to LARP as Tony Stark.
We Software Engineering types love to smack talk Bill Gates, but back when all he did was sling code he was astonishingly good at it.
The people who only know his current persona never knew “Microsoft Bill” or numerous business flubs. Sure Bill himself lucked into IBM’s miscalculation as to the potential of personal computing, but if he couldn’t make his code work on an (iirc) 4k ROM, he’d just be another Harvard dropout.
> I think many engineers would quibble with the characterization of Elon Musk as an engineer, let alone a brilliant one
Everyone who has claimed this has never met Elon, while every engineer or scientist who has actually met him agrees he's an engineer. As an engineer myself, I know which sounds more plausible to me.
My direct evidence is his series of interviews with the everyday astronaut where he ends up giving an impromptu 30min technical presentation about the raptor engine.
I've met my share of pointy-haired-bosses and they didn't know that level of detail on their own product.
"My usual heuristic is that when studies contradict, I trust bigger studies, more professionally done studies, and (as a tiebreaker) negative studies - so I leaned towards the studies finding no effect."
The debate really comes down to the validity of that heuristic. Trusting bigger, more professionally done studies would be a great heuristic if we assume corporate money does not corrupt scientific research. But this is of course a false assumption. I trust small studies done by doctors trying to treat patients in a third world country over large, professionally done studies brought to you by Pfizer.
I believe BigPharma is completely corrupt, and countless civil lawsuits and corporate criminal prosecutions bear this out. These corporations also corrupt the regulators, universities, and contractors who rely directly or indirectly on their patronage. In short, I rely on the Upton Sinclair heuristic - “It is difficult to get a man to understand something, when his salary depends on his not understanding it.”
Leaning towards negative studies would be a good heuristic in the case of patented and thus potentially lucrative drugs, but not in the case of generic drugs threatening a BigPharma income stream. Based on the foregoing, I don't have a strong belief that Ivermectin is effective as a Covid treatment, but I do lean in that direction based on the Upton Sinclair heuristic. You can go into all the studies and present critiques and counter-critiques until the cows come home, but it really just comes down to which heuristic you apply.
1. Big ivermectin studies have failed pretty consistently over long periods. You would need pharma companies to have meddled with studies from before their own drugs were ever approved, in the hopes that their drug would be approved later. And then after their drug had become standard of care, in order to prevent the previous meddling from being found out.
2. About 50% of Phase III trials fail. These are the big studies where pharma companies have already invested tens of millions of dollars into a drug, and now they have one big study to prove to the FDA that it really works. These studies are usually done by the pharma company itself, albeit with FDA oversight. If pharma companies can't even fix their own studies of their own drugs when tens of millions of dollars are on the line, why do you think they would so consistently bring out all the stops for a drug that *might* compete with their drugs later on?
3. Why did pharma companies let corticosteroids look good in studies and become standard of care for COVID?
1. I don't understand this claim. My understanding is a bunch of small trials showed promising results, then the Together trial was put forth as ending the question once and for all. Meanwhile, the Oxford trial ended under suspicious circumstances with no results forthcoming. I'm unaware of big early IVM trials repeatedly failing in the early days of Covid. And everything about the Together trial stinks. Putting forth an initial protocol of a single low dose of ivermectin cannot be reconciled with an intent to discover the truth in the best interests of patients. The initial Together ivermectin protocol was such obvious bad faith that one can't help but become extremely skeptical of the whole industry and everything that comes out of it.
2. BigPharma can only do so much. Obviously I'm not claiming there are zero checks. There are just inadequate checks and lots of ways around them. I would guess of the 50% of Phase III trials that succeed, most of those are actually garbage drugs, as most drugs are actually garbage drugs. I've been prescribed all kinds of garbage drugs (and now take none and am healthier than ever). Vioxx is of course exhibit A for garbage drugs getting through the system, and there's no reason to believe it was a real outlier. There's no reason to believe the Vioxx trials were conducted in a dramatically different way than other trials. In support of claim that most drugs are garbage, see, e.g., https://www.newscientist.com/article/2209477-why-most-new-medicines-are-no-better-than-existing-treatments/, https://studyfinds.org/big-pharma-fail-no-evidence-of-added-benefit-in-most-new-drugs-study-finds/. A high percentage of the "successful" trials are showing benefits that do not exist in the real world.
3. BigPharma can't tank every study. Sometimes real science happens, even in medicine.
4. I don't know why ivermectin became the target of BigPharma, the regulators, and the media to the extent it did, as opposed to other drugs and supplements. The whole campaign against ivermectin was bizarre, even if one accepts that it is an ineffective treatment. I'm not aware of similar campaigns against other treatments, and I have no explanation for the absence of such campaigns.
5. BigPharma is global. Yes, BigPharma can manipulate studies conducted in other countries.
Huh, I thought that the reasons for the media frenzy were obvious. The other side of the culture war happened to take ivermectin as their rallying banner, so the usual weapons were deployed.
Sure, but there were many other popular treatments. Indeed, the popular FLCCC protocol consisted of a cocktail of supplements and generic drugs, not just ivermectin. But ivermectin became the leading target.
"The whole campaign against ivermectin was bizarre, even if one accepts that it is an ineffective treatment. I'm not aware of similar campaigns against other treatments, and I have no explanation for the absence of such campaigns."
Were any other medications touted as a miracle cure by as many people as ivermectin was, with as little biological plausibility to support it? If you got a big fire, you need the big hose to put it out.
It seems to me that there is an isolated demand for rigor that was applied to Ivermectin that was not applied to the Pfizer vaccine, even though Ivermectin has a much lower side effect profile. Call me cynical, but I suspect this has to do with profitability.
The side effect profile is secondary when there are fundamental doubts about the efficacy of the stuff. A medication can be as cheap and safe as it wants - if it doesn't work, and the promise of it working keeps people from taking a vaccine that has been shown to reduce mortality by an order of magnitude, that is a problem (especially at a time while the earlier variants were circulating, which were deadlier, but more effectively suppressed by the vaccine than Omicron).
The Pfizer trial showed more deaths in the experiment group than the ontrol group.
(And Pfizer has a long history of fraudulent medical research.)
And in many cases, the jabs were pushed on people without informed consent. But please do link the evidence that the jabs reduced mortality by an order of magnitude along with the longterm safety data.
The side effect profile is crucial here. There’s no question that ivermectin is safe. Accordingly, there was no fire that needed putting out, anymore than there needs to be a war on vitamin C supplements. The proposition that ivermectin caused “vaccine hesitancy” is unfounded. True, many of the same people who believed ivermectin was effective also believed the jabs were dangerous. But this is a correlative relationship, not causal. Both beliefs are secondary to distrust of the establishment.
"Putting forth an initial protocol of a single low dose of ivermectin cannot be reconciled with an intent to discover the truth in the best interests of patients."
For the conventional use of ivermectin, a study found that a single dose rather than multiple doses was the best method. This may be why that was the initial protocol used.
"Interpretation: Multiple doses of ivermectin did not show higher efficacy and was tolerated less than a single dose. A single dose should therefore be preferred for the treatment of non-disseminated strongyloidiasis."
I suppose that could be put forth as a justification, but I don’t find it persuasive. Groups of doctors were putting forth specific ivermectin protocols, most notably the FLCCC protocol. The matter of public interest was whether those protocols were effective. All of those protocols called for much more than a single low dose. To deviate dramatically from those protocols and then offer your trial as debunking those protocols strikes me as bad faith.
With respect to Big Pharma, Big Studies, and the priors we should place on them, I think its imperative to consider the unitaid/Hill/Lawrie audio tapes.
Not only do we know of at least one high profile instance of monied interest putting their thumbs on the scale in a way that would make the most cartoonish-villain tobacco executive blush; what was perhaps more damning was the deafening silence around it. Not only can you do these things; we live in a world where you can do these things with zero consequences.
Its that silence in particular, that causes me to update strongly away from the Big Studies; which are the natural targets of monied interests, over the plethora of small independent studies.
@Scott Are you planning on adding Biber to your mistakes page? Anything where you have to write "I was egregiously wrong, and I apologize to the study authors and to you." probably qualifies. I'm not writing this as any kind of attack; I just want to see that page remain up to date because I think it is one of the keystones of your credibility: I can trust you because you will tell me when you've been wrong (and not just in the depths of some post that I might not have read, though that's already an impressive and unfortunately rare step).
I feel like this is the best post that could have been written about a debate so full of sound and fury (and in many dimensions, not signifying nothing). At one point I felt like my eyes were bleeding from the point by point depths of discussion. At another I was blessed by the novel exposure to funnel plots and their interesting and likely significance. And at another by the graph that doesn't think it's about publication bias. At all points by the way this all works as a parable about how to debate and how well meaning people can perhaps go wrong and what it looks like to keep doing it
I was familiar with Alexandros' arguments before your original post and I respect his general capacity and attitude. I always doubted ivermectin but I was interested in the debate and nowhere else did I encounter actual debate. You two win by default, but also by a mile. It's quite understandable that someone with a high personal stake in something so high stakes made some personal remarks - but it would be worthy if he took them back
There are no personal remarks from my end. Scott has slung several insults towards me, and he is aware that I don't believe I have ever personally attacked him, even if he has done it. He still chose to leave that language in this article. Make of that what you will.
Nothing much to say about ivermectin at this point, though I still find it amazing how ivermectin was able to get 100s of times more interest and noise than fluvoxamine, which was probably the better hypothesis among the possible repurposing candidates, and was being researched around the same time period.
In any case, I find it weird that you would call your own mistake "offensive". I know these days being offended is kind of fashionable, but what on earth is offensive about a honest mistake in the middle of a best attempt at an objective take on a complicated and hot topic?
Yeah I wonder why Ivermectin is the one that took off and got popular, developed a legion of believers and scientist defenders. Was wondering if it's because it would be better known in rural areas . Fluvoxamine, on the other hand, is an OCD drug, sometimes also used for depression -- so maybe people in blue states are more likely to know about Luvox, people in red about Ivermectin?
One reason could be that people can buy ivermectin for veterinary use without a prescription, whereas there's no legal way to get fluvoxamine without seeing a doctor.
> would I bet even money that they'd see "statistically significant" 10% reduction in mortality? Thinking about it as hard as I can, If I felt I could trust the scientists to not pull any dirty tricks, I think I still would, yes.
I am impressed to see an answer that's not a panacea complex.
This is so different than what IVM fans were saying in 2021. Bret and Pierre were talking about using IVM to drive covid to extinction on Rogan that year. Pierre was going further saying it's likely to be a general purpose antiviral.
If people had said "take this in reasonable doses and maybe it shaves a few days off" the 2021 discussions would have went so much more smoothly.
Youre confusing the use of ivm as prophylactic against the earliest variants in a seronegative population with the use of ivermectin against omicron as early treatment in a mostly seropositive population.
That said, the extinction thesis was probably wrong when it was articulated, even just considering sars-cov-2 had spread to animals such as deer.
Not confusing them, comparing a reasonable take on its potential for treatment to the much much more unreasonable “not only is it a treatment, it’s a general use antiviral.”
Point being, if you had went on JRE in 2021 and said I think there’s a 50/50 chance of IVM lowering mortality in a very well-designed study, I would of had zero problem with that statement.
The avatars of ivermectinism were making much grander statements than that much earlier on.
Sure. Just keep in mind that essentially everyone recommending ivermectin was doing so as part of an extensive multi-drug protocol, so the various hyperbolic statements you've probably heard are ones selectively taken out of context, or ones corrected shortly after they were made, and were always contradicted by what was being recommended to people.
That podcast was perhaps the exact moment where I went from being a Bret fan to being like"OH MY GOD BRET WHAT THE FUCK HAPPENED TO YOU!?" And that was when I stopped paying much attention to him and others in that camp. There might have been some value in continuing to track their intellectual progress, but there's only so many hours in a day and I wanted to find the best signal to noise ratios in the pandemic. I hope he updated and I hope he can let go of some of the pandemic takes.
For all who could use a little comic relief at this point, here are 3 DALL-E images of the Ivermectin debate. The prompt was "two men having an intense debate about a medication for intestinal parasites."
Good heavens - what a waste of time on balderdash and trying to play it through disagreements on statistics.
Where the hell were you when the Pfizer and Moderna info had to be forced by a judge to release it within 75 years ?
You can say what you believe and I will continue to believe what I/ we my spouse and 7 members of a Vet’s coffee group have experienced.
We have been on prophylaxis dose of IVM for nearly three years, surrounded by Covid victims in our daily lives, close contact with positive testing individuals.
A coffee group meeting every MWF every week for many years - 7 members have all gone thru their 3-4 x Covid infections and all have treated with IVM at proper 0.2 - 0.4 - 0.6 mg/kg doses as per flccc.net protocols excepting they took the 0.6 mg when having Covid to get over it but then stopped the regular dosage after getting well with a 5 - 7. day course of therapy, only to gain another Covid infection several months again later.
You can browbeat and try stats to kill off IVM but we will continue our usage for prophylaxis for as long as the idiocy continues.
You would be better served and maybe be accepted more readily if you chose to use the fraudulent results
Of Pfizer, Moderna et.al 60 day trials which more align your thoughts.
You keep your results and we will keep ours and obviously never the twain shall meet.
But we know our friends and fellow IVM users will be around to meet again and again as against the bullshit you keep trying to kill it off while ignoring the works of RCT’s with proper dosage and protocols.
"You can browbeat and try stats to kill off IVM but we will continue our usage for prophylaxis for as long as the idiocy continues." Jeez, miner, if you really think the stuff protects you I don't think you should only keep taking it as long as "idiots" like Scott keep making the case Ivermectin doesn't work. That would be a sign you are mostly taking it to defy Scott -- you know, like a teenage guy dying his hair pink to upset his mom. I really think you should keep taking Ivermectin as long as you believe your health is in danger.
You might take notice that I could take this post, replace ivermectin with some alternative medicine thing you don't believe in, and you would probably laugh at it.
I think you misread his comment as saying he never got COVID but he actually got it 3 or 4 times, he just didn't die from it (what I assume he means by 'covid victims')
Wow, a coffee group! Yeah, that beats everything else for rigour and repeatability!
Look, I'm glad you and your friends didn't get sick. Except for those of your friends who did get sick.
I and other family members also got sick. We didn't use ivermectin and we got better the old-fashioned way (by suffering through it for a week or ten days, then it cleared up). It hit us all differently, for a couple it was no worse than a cold, for others it had worse symptoms but different ways.
So seven of your group got recurrent infections and got better again within a week. Just like the ordinary way of getting better. This doesn't mean ivermectin cured them.
Keep taking the cattle drench, it won't do you much harm and at least you'll be free of worms!
Well I personally have been taking 8 fl oz of brown ale once a day in the evening after dinner as a prophylactic against COVID, and by golly it has worked, I haven't gotten the bug even once, even though everyone else in my household did. So ha ha to your nasty deworming pills, I've got a prophylaxis that works just as well but tastes great!
Don't get me wrong I'm not saying IVM is a miracle drug but we keep asking for THE RCT study on IVM efficacy, knowing that it won't happen. No incentive to do it and a huge one not to.
Leaving patients untreated because there is no available RCT that determines its 'super effective and should be used worldwide'.
Look how long it took the USA hospitals to include sterocorticoids in their "treatment"
Did the medical community not know they help with inflammation??
I realize I'm derailing and you are actually focusing on the IVM published studies, but the bigger picture paints the context in which most of this
People died from bacterial pnemounia while we were too busy playing statistics
There have been four really big, extremely professional RCTs of the sort that would usually be considered Phase III trials (I think, not totally sure about the terminology) for ivermectin now. All of them found no effect. We're not waiting for THE RCT, it's already happened, multiple times. I agree if there had never been any big RCTs it would be reasonable to try it prophylactically.
Thank you for replying, you're right I phrased that wrong.
My point was more on the subject you already discussed with 'David' in the comments; regarding studies parameters and how we can manipulate variables to show the effect we are looking for...or no effect at all.
Admittedly I am pretty biased leaning pro IVM, really wish studies would/could show how it is an effective treatment option.
Here in Mexico we saw lots of patients quickly recover or had a pretty mild infection when treated early (tho IVM is not alone here). And we've seen the potential protective mechanisms of action in vitro. Correlation is not causation but there were just too many correlations not to take the signal seriously
Lots of patients with no medication recover quickly or have a pretty mild infection, especially now, because most people have had covid and many have also had a vaccination. Case fatality rate is way way down.
Given that ivermectin was so deeply plugged into the larger COVID conspiracy nexus, in which the pandemic was some combination of (Chinese bioweapon/not that dangerous/media invention/5G side effect/easily treated with horse medicine) done to (usher in world government/make money for pfizer/hurt Trump's campaign), I'm finding it incredibly hard to even care about the debate now that the pandemic is functionally over basically everywhere except China, which is already a semi-totalitarian state anyway.
Your initial post on this in Nov 2021 was a revelation. Thank you very much. This is far outside my field, and yours was an exhaustive review of the evidence to date on ivermectin (such as it were), as well as a summary of Dr. Bitterman’s fascinating hypothesis. I shared it with many colleagues. What a great read.
Well done here to respond to one of your strongest and most committed critics on this file. You’re not looking for pats-on-back but should get some anyway. Not every day you see mea culpa’s as you’ve done here. It’s a strong show of character.
On the science of ivermectin, however, it boils down to a simple first principle for me: the scientific method. The burden of proof rests with those who propose ivermectin to be of benefit. Until such time that they can provide causal proof of “benefit” via an RCT that reaches statistical (and also hopefully, clinical) significance, the only solution is to accept the null and reject their “hypothesis”. Anything else is just noise.
I’d also add that the requisite standard of proof needs to be met for any and all potential “use-cases” of ivermectin, such that there is no conflating btw prophylaxis and treatment; or of minor vs severe illness; early vs late; on O2 vs not; the list goes on. “Proving” a treatment “works” is a tough slog. It’s no wonder the ivermectin crowd shied away from it. Which is too bad, since globally they had the time to do many poor studies that were never going to be sufficient to prove causation, whereas that time should and could have been more gainfully spent on protocols that at least had a hope of answering the question. And of course, the later and typically western RCT studies showed no benefit.
As for the “wager”, that is silly talk best reserved for religion than for medicine (as you rightfully suggest). We don’t prescribe things that are useless just because they are safe. Your critic’s “wager” belies his religious fervour for ivermectin, in the absence of (appropriate) evidence.
It’s people like your good self that kept air in the conversation, many of us knew something wasn’t right and while it was obvious you would be attacked I commend you for standing your ground.
> But it got results p = 0.001, and you would need a thousand studies in file drawers to produce one like that. Weird.
I'm not sure if I'm teaching you to suck eggs here, but a p-value doesn't report the probability that the two groups in a trial have the same effect in real life, but rather the probability that the observed differences are due to chance. So a far more common reason to see a p-value like this conditional on ivermectin having no effect would be some subtle error of trial design like a loss of blinding or statistical error in the analysis.
It seems entirely plausible to me that an equivalent study that made a coinflip statistical error leading to p=0.999 wouldn't get published, so you only need to worry about the existence of one hypothetical unpublished trial, not thousands of them
I agree, but my claim was that I looked pretty hard for other errors, couldn't find them, and if I wanted to attribute it to publication bias alone it was a 1/1000 chance. I agree the most likely explanation is some completely hidden error that left no trace.
1. Thank you for the follow-up. Yes, in 2023 all work on ivermectin vs. covid looks pointless - but a lot generalises - and in Germany, Ivermectin was never a big thing in the public discourse to begin with (though at least Austrian pharmacies were sold-out, at times.)
2. I still feel your post was at least A- by content, not C. But sure, standards differ. This is the No1 substack on science - actually on rta - but still no habilitation. And no infamous NYT/WaPo.
3. The Carl Sagan/Pinker thing: Stuff must be true, but truth must not be boring. Your original post was not just very, very educative, it was hilarious. I was literally lol when reading and smiling for weeks after. Although on first clicking it, I doubted I would finish that post (that crazy worm-medicine? Dozens of studies reviewed? Meh. ) I would never have read this follow-up, if the original post had bored me.
Completely off-topic, but I'm curious how a name like "Meyerowitz" comes about. -owitz is obviously the Slavic patronymic marker -ovich, rendered into German where the ch sound doesn't exist. Patronymics are based on the father's personal name.
So the suggestion appears to be that someone named Meyer had a son in a Slavic country who took an ordinary patronymic, that patronymic was somehow reinterpreted as a family name, and then at some point someone from the family moved to Germany. (Or, possibly more likely, someone of an unknown name started a dynasty in... say, Russia, they used normal Russian patronymics alongside their weird Jewish names the whole time they were there, and then eventually someone whose dad had been named Meyer moved to Germany, where everyone forgot about his family name and reassigned his patronymic to serve that purpose?)
Does anyone know which of those events likely happened in what order, and when/where the "Meyer" spelling is likely to have been introduced? I see on wikipedia that Meyer Lansky was originally named "Maier", which I assume can only have been pronounced exactly the same way as "Meyer".
Or am I interpreting "Meyerowitz-Katz" as a two-parent surname when in fact it's a completely normal patronymic accompanied by a completely normal surname, hyphenated for no particular reason?
OK, but it also means that at some point their family name, if any, was replaced by a name that is most certainly not their family name. That seems unlikely to have happened in Poland (but see below), where people would have understood what "Meyerowicz" meant. Did it happen to a big group of emigrating Jews all at once? Did it happen to a bunch of individual families over time? Did it in fact happen in Poland? I see there is a current Polish MP by the name of Jacek Włosowicz, while their MPs generally don't have obvious patronymics, which suggests the system may have fossilized inside Poland. Perhaps it did so over a relevant time frame?
What was the state of standardized spelling at the time? Would a Pole who naturalized in Germany today be assigned a respelling of his own name?
"Would a Pole who naturalized in Germany today be assigned a respelling of his own name?"
I can say with certainty that the answer to your question here is: Definitely not.
A lot of European Jewish names got mangled when the people moved to English-speaking countries, famously at Ellis Island but not only there. The person in question is Australian, so I can imagine the authorities in Sydney having a difficult time with Polish orthography and just trying to get it close enough based on what they thought they heard. Speculation of course.
Studies of the records indicate that names weren't changed at Ellis Island, where officials were matching with written documents, but later, usually by the families themselves.
This isn't exclusively true. My great great grandfather was Swedish and had been Carlson but took Svade (sometimes Swed) suggesting, perhaps, it just means "Swedish" when he arrived at Ellis.
I have family lore suggesting my mother's grandfather immigrated to the United States and commented that they'd gotten the spelling of his name wrong, which he was happy about. He would have had written documents (in fact, we still have documents of his).
The -ovich to -ovits sound shift is not plausible as a result of moving from Poland to Australia, since English already has a CH sound. (All Slavic languages including modern Polish use some kind of CH sound for this; it seems safe to rule out the idea that the Polish of the time had "ts" instead.) "-owitz" spelling has to come from Germany. (Or, I guess, some other German-speaking country?)
Why do you think that "son of Meyer" is a less likely surname than "Johnson"? If we're being picky, "Johnson" is a patronymic which has become a family name.
"Meyerowitz is a double patronymic, in which both suffixes (the Russian "-ov" and the Polish and German "ow" and the German "-itz") mean "son of", making the literal translation of Meyerowitz: "son of the son of Meyer". Meyerowitz is based on the Yiddish Meyer/German Mayer (literally "farmer"). However, as a Jewish family name, Meyer is usually a form of the Hebrew male personal name Meir. In talmudic times, people credited with bringing light or intellectual clarity to their subject were given the name Meir (Hebrew for "illuminates or radiates" or "one who sheds light"). A 2nd century, disciple of Rabbi Akiva, believed to have been named Mesha or Nehorai (the Aramaic forms), was known as Rabbi Meir because of his keenness in shedding light on the Halacha (the Jewish code of law). Associated Jewish family names are Yair ("will illuminate") and the Aramaic Nehorai ("light") or their variants and patronymics. Similarly, the names Uri and Shraga (literally "fire"). Meir is documented as a Jewish family name in Arles, France, in the 13th century. It appears as Meiger and Meyger in the 14th century in Strassbourg, as Meyr in 15th century France, as Maier in Germany in the 18th century. Other variants include May in Germany and Poland, Major in Turkey, both in the 16th century, Mayer in France and Germany, and M'riro and Merito in Morocco. Named for their forefathers, families were called Meyerson, Meyerovitch, Meyrowitz, Merovic and Ben-Meir, all meaning "son of Meir".
Another short version has it:
"Meyerowitz Name Meaning
Jewish (Ashkenazic): patronymic from Meyer. The ending -owitz is a Germanized form of the East Slavic patronymic ending -ovich Polish -owicz."
So family name Meir/Maier gets further altered in Germany and/or Poland as "Meyerowitz".
There has obvoiusly been a lot of linguistic confusion in the shared realms of polish, german and yiddish speakers. Transcription/Pronounciation rules differ (Szulc=Schulz for example) and the hebrew consonantal writing may have also contributed.
Very minor point, this sentence: "Ivermectin was originally an anti-parasitic-worm medication before being repurposed to fight COVID, and everyone agrees it is very good at this," is a bit confusingly written, because it's not clear what 'this' refers to. Later parts of the text clarify, but maybe you want to tweak the sentence in case someone decides to quote you out of context again.
Thanks for writing this up! I've actually mildly adjusted the other way after reading this, to be perfectly honest (and rather unexpected going in), but I think it's a good sign for rigorous reporting.
"Doesn’t this mean that the medical establishment wants to blame Cadegiani both for giving drugs that don’t work, and for not giving them to enough people?"
The main points were that he had ethics approval for a small study, on mild/moderate patients, in a single hospital in the Brazilian capital, and somehow the study ended up being conducted in several hospitals, in critical patients, in the Brazilian Amazon. Also, the consent forms handled to patients were not the same as the ones initially approved, and didn't contain many passages about patients rights.
This study had a 50% mortality rate in the control group, with a significant amount of hepatic and renal failure. The author says they were in the placebo group, but that wouldn't have been known as the deaths were happening, as it was a blind study and there was no effort on the part of the author to request unblinding to check if maybe the renal and hepatic toxicity was because of the maybe renal and hepatotoxic drugs. When requested, the author did not provide any data to provide the traceability of the medication, so it can't be ruled out that the placebo group was actually receiving medication. The "Independent data monitoring comitee" in the study was under the supervision of someone on the payroll of the pharmaceutical company making proxalutamide
So, either the study was properly blinded and he decided to not report excess Kinsley and failure deaths which could presumably be linked to the new, barely-tested drug, which would be a crime, or he knew that the placebo group had an overwhelming amount of excess deaths and didn't try to prematurely end the study, causing willful harm to the patients, which also would be a crime
I haven't been able to find any news on the subject since the police raid on the author's house last August, but this is unsurprising given the slow pace of the Brazilian justice system
> … or he knew that the placebo group had an overwhelming amount of excess deaths and didn't try to prematurely end the study, causing willful harm to the patients, which also would be a crime
I must be misunderstanding this sentence. How could ending the study have prevented harm to the placebo group, who were not receiving any drugs as part of the study? If the placebo group had lots of deaths, surely that can’t be because of the study, which only gave them a placebo … so stopping the study can’t help them … and continuing the study can’t harm them.
The author only observed excess death, and is blinded to whether the patient got placebo or not. So it is unethical to continue considering the excess death could be from real medication.
Considering the amount of excess death [50% (of what?) which is way higher than base line] and the possibly dodgy tracking mechanism. It is possible that the real medication might have cause the excess deaths and those deaths were later shunted into the placebo group causing the abnormal reporting.
Or he may have found the golden cure and refused to stop the trial leading to excess deaths.
50% of the patients in the control group, which consistent of hospitalized patients, not on mechanical ventilation, with a median age of 50 years, and 70% of which had no comorbidities, were dead after 28 days
This is a high amount even on patients receiving intensive care, which tend to also be older and sicker
Oh, I get it. If the study was improperly blinded, so that he knew who was in the placebo group, and he saw that they were having massively excess death, he should have given them the drugs the other group was getting, which would have seemed to him really effective and life-saving. Doing that would have ended the study, by definition.
" The whole “repurpose existing drugs against COVID” idea seems to have been a big wash. "
I would paraphrase as:
"Because !IVM, and perhaps !FLV , then the space of all existing drugs & compounds prior to the advent of COVID at any dosage regimen are very unlikely to show any safe efficacy against COVID morbidity or mortality."
Would you mind characterizing the statement further?
I don't want to speak for Scott, but that is not a good paraphrase. You're claiming that Scott implicitly says, "among the many thousands of drugs that were not known to be useful against respiratory viral infections, there is probably none that is effective against COVID" - when the more realistic implied statement is "when you select and try a few out of the many thousands of virus-unrelated drugs, without a solid biological mechanism to guide the selection, you are unlikely to find one that works"´, and the literal statement is "the couple of (virus-unrelated) drugs that were selected and tested for COVID turned out to be duds."
So in my read both of the latter two statements are cheems as set against SA's swole dog statement.
We're also somehow seeing the exact same statement and interpreting it in two very different ways. Is the 'a big wash' vernacular implying that the search for repurposed drugs for the pandemic wasn't worth undertaking in the first place? Or does it just mean that the results of the repurposed drug search enterprise, in the way that we collectively went about it looking back, did not yield useful results (itself a debatable statement IMO, but that's beside the question at hand).
I normally interpret something being called "a wash" as meaning that it turned out to have no effect. I can't recall any occasion where I believe it was intended to mean "you should have known this would have no effect before you tried it."
But even if you interpreted "wash" that way, that seems to map squarely to FluffyBuffalo's suggested reading of "when you select and try a few out of the many thousands of virus-unrelated drugs, without a solid biological mechanism to guide the selection, you are unlikely to find one that works".
I don't think a plain reading of this statement says that.
If I combine it with other things Scott said in this essay to form a gestalt impression and make a prediction based on that, then I predict that Scott would say that a future search is unlikely to succeed unless it has a stronger basis for selecting which drugs to investigate than this search had. But I'm not super confident in that prediction and I don't think Scott is making any specific effort to build that case.
Also, if your question is meant to somehow imply or build towards some argument supporting your original interpretation, then I don't understand where you're going with it. Even if I answered an unequivocal "yes", that would still seem more in line with FluffyBuffalo's suggested reading than yours.
As always, I appreciate Scott giving a hearing to folks with different perspectives, and I especially appreciate his integrity in transparently engaging with his mistakes and with points won by the other side. That said, it is hard for me to see the potential value in this discourse, for two main reasons:
1. I don't think that litigating and dissecting the reported details of 1-2 dozen small positive studies has scientific value. If there's anything we can learn from The Control Group is Out Of Control (https://slatestarcodex.com/2014/04/28/the-control-group-is-out-of-control/), it's that the epistemic value of scientific studies is much more limited, conditional, and contextual than we would like. Deep dives into the reported protocol don't necessarily help. Shoveling a bunch of small studies into a meta-analysis doesn't necessarily help, if their internal issues combined with the file-drawer effect are sufficiently severe. Genuine epistemic progress simply requires better studies with larger samples, more reliable protocols, etc. I am not aware of any instance in which applying overwhelming brainpower to small studies has produced scientific progress. It seems to me that, by the time we get around to the Conclusions on this post, Scott has basically come back to his 2014 SSC post. We know this style of science doesn't work because it can be leveraged to prove anything, no matter how nonsensical.
2. I place low trust in Alexandros as an epistemic agent based on heuristics I consider reliable. Alexandros' posts are saturated with emotional, dramatic, adversarial language, and he spends a visibly disproportionate amount of time litigating points of very marginal relevance. I have seen this pattern frequently online, and it is a strong signal of low-quality thinking. The fatal temptation of polemicists is to become obsessed with winning at the expense of truth. In their sprawling, point-by-point refutations of their opponents, it quickly becomes impossible for a third party to discern what the original point of the discussion was, or how the points currently being discussed tie back to it. It's hard for me to say what I learned from this post, except that even Scott, with his extraordinary thinking and writing powers, cannot turn a discussion of this type into something illuminating. I'm glad Scott emerged from the morass with some lessons, but it's hard for me to say the same.
I think it is time to invoke Shaw's adage about wrestling in the mud with certain hooved animals and move on.
The Biber et al. study looks interesting and is the one most likely to shift my opinion towards "maybe ivermectin does have a specifically anti-covid/anti-viral effect as distinct from killing off parasites which enables immune system to do better fighting the virus", but it's still "early treatment of non-hospitalized patients with mild COVID-19", so that tells us nothing about "can it work for severe cases?"
But I am solid on Flavio A. Cadegiani, M.D., Ph.D., M.Sc. and his alleged gold medals don't impress me much:
"His superlative achievements include amongst the fastest PhD obtained in the history of Federal University of São Paulo (7 months) and concurrent gold medals in Mathematics, Chemistry and Physics Brazilian Olympics in his adolescence."
I remain to be convinced about getting a PhD in seven months, and there seem to be a lot of different Brazilian Olympiads so without knowing which ones he entered, it's impossible to say if he did win what he claims, or if the particular competition was ranked highly.
As to his covid treatments, he didn't simply stick to ivermectin - he was pushing for an anti-androgen as another miracle cure, except unhappily that study got pulled for bad methodology (and he seems to have gone for the anti-androgen *after* the ivermectin work, so not reliant on ivermectin as being the sole single cure):
"Violations of medical ethics and human rights committed in a trial of an experimental drug touted by President Jair Bolsonaro as a cure for covid-19 were the worst in Brazil’s history, the country’s research regulator has said.
The clinical trial of proxalutamide “disrespected almost the entire protocol” and may have contributed to the deaths of as many as 200 people, said the National Health Council (CNS), which oversees clinical research in Brazil. Some of those people were not adequately informed of the risks they were undertaking in the trial, and some did not know that they were taking part in one, it said.
Brazil’s attorney general is investigating the possible violations of medical ethics and human rights on the recommendation of the National Research Ethics Commission (CONEP), which forms part of the CNS. The trial’s principal investigator, Flavio Cadegiani, was identified in October along with 68 others by a parliamentary inquiry into Brazil’s management of the pandemic as having committed “crimes against humanity.”
Proxalutamide is an anti-androgen that blocks the function of some male hormones. It is being tested by China’s Kintor Pharmaceuticals for prostate cancer, breast cancer, and other uses. It has not been approved for use in any country but was talked up by Bolsonaro as a treatment for covid-19. Shortly after recovering from covid-19 he asked why it had not been approved for use and promised to make it available to all of Brazil."
There's also the "conflict of interest" disclosure about Dr. Cadegiani, et al. on the ivermectin study:
"Lucy Kerris is a paid consultant for both Vitamedic, an ivermectin manufacturer, and is co-founder, as well as acting as a paid consultant, for Médicos Pela Vida (MPV), an organization that promotes ivermectin as a treatment for COVID-19 and discourages COVID-19 vaccination. Flavio A. Cadegiani was a paid consultant (USD 1,600.00) for Vitamedic, an ivermectin manufacturer. Dr. Cadegiani is a founding member of the Front Line COVID-19 Critical Care Alliance (FLCCC), an organization that promotes ivermectin as a treatment for COVID-19. Pierre Kory is the President and Chief Medical Officer of the Front Line COVID-19 Critical Care Alliance (FLCCC), an organization that promotes ivermectin as a treatment for COVID-19 and discourages COVID-19 vaccination. Dr. Kory reports receiving payments from FLCCC. In February of 2022, Dr. Kory opened a private telehealth fee-based service to evaluate and treat patients with acute COVID, long-haul COVID, and post-vaccination syndromes. Dr. Kory expresses personal points of view against COVID-19 vaccination. Jennifer A. Hibberd is a co-founder of the Canadian Covid Care Alliance and World Council for Health, both of which discourage vaccination and encourage ivermectin as a treatment for COVID-19. Juan J. Chamie-Quintero is a contributor to the Front Line COVID-19 Critical Care Alliance (FLCCC), lists the FLCCC as his employer on his LinkedIn page, and expresses personal points of view against COVID-19 vaccination."
He may well be an expert in sports medicine (though it would seem easier to be an expert in a field where you're writing the majority of the works) but I don't think he is trustworthy re: "don't get vaccinated, take my miracle cure instead":
"Dr. Cadegiani is the only author of the sole book in Overtraining Syndrome, the prevailing sport-related disease among amateur and professional athletes. He is also responsible for approximately 70% of the articles published in the field in the world in the last 05 years, and reviewer for more than 90% of the manuscripts in the field."
FYI, most of the doctors advocating for ivermectin were recommending multi-drug protocols such as the one by FLCCC or McCullough. I have yet to see one recommending only ivermectin and nothing else if you get COVID.
I'm just letting you know of factual evidence that the whole "miracle cure" story was wildly overplayed. Obviously the people putting together those protocols wouldn't describe them as you did, but that's a separate matter.
I am shipping sugar pills as ivermectin from India. This should have no impact on your protected-ness from Covid. On the other hand, if you have worms, please phone us immediately.
You may as well, since the Indian government dropped their recommendations for ivermectin and hydroxychloroquine in 2021 as they didn't do a damn thing. They probably have a stockpile of drugs they might as well sell to gullible Westerners and get some return on their money.
"The Indian Council of Medical Research (ICMR) and the National Task Force on Covid-19 have dropped the use of Ivermectin and Hydroxychloroquine (HCQ) drugs from their revised guidelines for the treatment of the infection.
The decision was taken after experts found that these drugs have little to no effect on Covid-related mortality or clinical recovery of the patient.
“HCQ may be considered for removal from guideline, with recommendation to use with caution only in clinical trial setting (since there is some genuine uncertainty regarding the possible benefit for severe cases and in low dose),” said the document titled ‘considerations for exclusion of Ivermectin and Hydroxychloroquine from the clinical guidance for management of adult Covid-19 patients’.
Several clinical studies have shown the low mortality benefit for HCQ, said the document. In fact, when HCQ is administered with azithromycin, it increases the risk of adverse drug effect (ADE) in patients, experts said."
"In response to this section, Alexandros stresses that he is not necessarily saying Borody et al is incorrect or challenging my decision to leave it out." -> probably meant to be: [..]Borody et al is correct[..]
"[..] authorize it, it (according to Carvallo) it is [..]" -> one less "it"
> Alexandros has grappled with this same mystery, and taken a different route, Alexandros has wrestled with these same problems, but solved it differently.
Scott, I do not need to tell you that you are an extremely talented writer. Why do you waste your precious skill and time answering to somebody without the credentials?
The TOGETHER trial, published in NEJM 2022 was negative. Done. This is the one observation that refutes the hypothesis that Ivermectin decreases hospitalization rate in patients with Covid-19. And it was done in Brazil, one of the countries with the highest prevalence of Strongyloides.
Much appreciated. I have a good impression of Alexandros's efforts in much of this and feel your post added further insight and nuance, regardless of one's prior.
A side of this I'd like your take on:
For me it seems not at all clear that Ivermectin would have an effect today. For one thing, Pierre Kory and many associated with him shouted a preliminary alert when delta was appearing, that it seemed ivermectin might not be nearly as effective on that variant and that all prior indications of likely ivermectin effectiveness should not be trusted absent new data from Delta and onwards.
1) Off the top of your head, does it seem probably to you that ivermectin was initially effective and a missed opportunity on the original strain but lost most/all of its advantage after variants?
2) Whether ivermectin is effective or not, seems very murky to me and ultimately of much less interest than whether our institutions acted appropriately by the data available. Much clearer than whether ivermectin is effective, I have a strong sense that there was a significant signal with low cost and risk that institutions were failing to explore and in many cases discrediting in deceitful ways. Do you have any thoughts on how appropriately any early indications were acted upon?
"The whole “repurpose existing drugs against COVID” idea seems to have been a big wash."
Dexamethasone is cheap and repurposed and is still one of the primary treatments for hospitalized covid patients requiring high-flow oxygen. This was confirmed with an early RCT from the RECOVERY trial.
is there an "undeniable unbreachable fortress of evidence" for the Pfizer vaccines?
Why is that the standard for IVermectin but not for the newfangled, non-immunizing treatments that causes heart attacks but are still mandatory. (i.e. Pfizer/Moderna vaccines)?
The result is claimed to be strongly positive for early treatment. Does it contradict any "high quality" trials? I think ACTIV6 and TOGETHER were later interventions. The devil is in the details, and Alexandros' takedown of ACTIV6 was convincing, especially as regards the study authors' mixing up of Bayesian confidence (ideally 1) and p-values (ideally 0). https://doyourownresearch.substack.com/p/activ-6-trial-ivermectin-scientists
FWIW, I also respectfully asked the corresponding author about a seeming inconsistency in the paper (by email from a top .edu address). No answer.
>I will repeat that my strong objection, is that you wrote " this is not how you control group, @#!% you". I therefore pointed to stat news to support my case that, yes, this can indeed be how you control group. That's all. In the article I even noted that this aversion towards disrespect to elders may even be a cultural difference between us. To be clear, if I were making a case for ivermectin, I would not be relying on this study as my starting point.
Okay, but I have to ask, what *is* Alexandros making the case for? Is he trying to make a case for ivermectin, or simply saying that you're being insufficiently respectful to the people who study it? Because "This methodology exists and is used in a couple of specific cases that have nothing to do with ivermectin" is irrelevant for the first, but a 21-part essay titled "The Potemkin Argument" seems a little overboard if all he wants to say is that Scott is sometimes snarkier than he should be.
In general, Alexandros's responses give me the impression of "JAQ-ing off" - switching back and forth between "Here's the case for Ivermectin" and "I'm not making an argument for ivermectin, just pointing out some methodological issues on the anti-ivermectin side" depending on how well each individual part of the argument holds up. But if you start off by comparing your opponents to Russian propaganda, then I'm going to be a bit dubious that you're approaching this in a spirit of collegial truth-seeking.
The case I am making, which you will see in the piece Scott is responding to, is that Scott's original piece is riddled with factual and logical errors, (which I document with specifics) and in addition, maligns honest scientists, while not displaying a fraction of the rigor he demands of them. What's more, my most deep disappointment has been with the rationalist community, that not only has not pushed back on a piece this influential and this wrong coming from one on their own, but if anything seems to endorse it.
This is impressively detail oriented. It also maybe loses sight of the framing of this whole discussion.
Marinos' arguments are merely the motte to Weinstein's bailey.
Marinos argues that we should simply take a chance on ivermectin treatment, because it's harmless and it seems like it maybe works, if you squint at the data just right and disregard all the largest trials as corrupt.
Weinstein argued that we could stop the pandemic by using ivermectin, that the suppression of ivermectin proves that the institutions are captured by big pharma. Along with many others, he argued that you shouldn't get vaccinated because vaccines are unsafe and ivermectin is at least as effective.
Marinos, sites like ivmmeta, and no shortage of other Substack writers offer just enough rigor for that argument to be plausible.
I originally took an interest in ivermectin because some of my friends and family bought that argument. They did not get vaccinated, they caught covid, they bought hydroxychloroquine and ivermectin from some telehealth providers. None of them died. But they got plenty sick and didn't recover quickly. It sure didn't seem like a miracle cure.
In that case, we've moved on from Omura's wager -- "if it's even 10% effective, ivermectin could save so many lives". We've moved to, "is it as effective as the covid vaccines?"
As of 2021, the FLCCC recommended ivermectin as the primary treatment for covid and briefly suggested you talk to your doctor about maybe getting vaccinated, almost as an after thought. As of today, I believe they recommend not to get vaccinated at all. In fact, Dr Kory now recommends against vaccinating children for any diseases, not just covid:
And, of course, Omura's wager was always a forced binary, so the motte itself is hard to defend.
Scott explained this well in "Pascallian Medicine" -- you could make the same argument for taking any and every reasonably safe drug when you get covid. Maybe one of them helps? Who's to say otherwise? Why not take 20 drugs?
Had I gotten covid in 2020, I would have gone ahead and taken vitamins, zinc, aspirin, low risk things like that, despite having low certainty that they would help. But I never understood why ivermectin moved to the top of the list of things to experimentally take. What made it any better than other speculative treatments, like fluvoxamine or metformin or bromhexine or camostat? Just the popularity on Youtube?
If ivmmeta's methodology for evaluating drugs is correct, why do we even need ivermectin? They think quercetin works just as well and melatonin is close.
Where were all the podcasts telling people to take quercetin and melatonin? Wouldn't those save more lives?
I suppose the government can't suppress those drugs, so you can't make a conspiracy theory out of any of them. And you'll get a lot less Substack subscriptions that way.
Remdesivir was a repurposed drug that proved to be highly effective (but expensive and impractical, since it only worked well if injected early enough)
I still wonder if the related drug GS-441524 could have also worked as an oral version. I'm not sure, maybe you can't hit a high enough concentration that way.
And I wonder if there are drugs we missed entirely, by not testing them in large enough trials.
I think there are still a lot of good questions.
One is why "early treatment" supporters haven't pivoted to metformin:
I think the answer is easy: Most of them are selling blogs and videos, so they need to talk about popular topics. Vaccine and ivermectin conspiracies will remain the product for as long as it's the most lucrative thing to talk about.
It also raises more important questions, like: what's the bar for getting the FDA to actually care about a generic drug? Would a second trial confirming COVID-OUT's metformin results be enough? Can that be done in under a year? Is it possible to still get statistical significance now that the virus isn't killing as many people?
In general, it seems like we need a breadth first search for treatments that isn't biased to approve a patented product over a generic. And we need that search to work a whole lot faster, if it's going to save any lives in the next pandemic.
Right now we have one process that works pretty well for patented drugs. And we have some sort of chaotic process that throws lots of attention towards whatever's popular on Youtube. Is there some third approach which could find cheap treatments faster?
Quick question. All I wish to know about ivermectin- is the risk/reward ratio worth taking? You appear to be conceding a sizable amount of your early analysis to rather embarrassing (your words. I'd call it credibility suicide, but I'll go with your description) yet somehow claiming a stronger argument on your own behalf as a result..
This reads more like a last ditch ego stroke to satisfy your own fanboys than a refutation of his work. He has put in the effort and done the math. I would not judge him to be pro ivermectin, simply because he proved you wrong.
At the core of this debate, there seems to be no disagreement. You were mistaken on multiple points. There is no value in your concession or apology if the end result is merely to assuage your own guilt for failure to analyze the situation beyond the popular media tropes. .
You have defended the popular belief, poorly, and when eviscerated for your inability to reach a conclusion which matches the facts, you've responded with even less facts, yet still declared victory.
I have heard of you as an example of the rationalist community, but I think you may have left some letters off the self assessed title. Clearly this is rationalization and nothing more. Title yourselves appropriately, please.
Also a couple direct criticisms-
"In contrast, the pro-ivermectin side did an amazing PR job. "
You mean the side that didn't have a billion dollar advertising subsidy to promote itself and was maligned by every institution, agency, and media conglomerate with access to a broadcasting. antenna won the pr war on this one? On one side you have billions of dollars of efforts and an infrastructure built on concepts of Total Information Control and Awareness and the other side have Joe Rogan and Joe did an amazing job? That seems rational and reasonable.
"I give myself a C+ for results but an A for effort. I wish other people would do this so I could stay in my lane of sniping at people with bad opinions about antidepressants."
If everyone gets a trophy? Sure. You got it big guy. Take 5 gold stars for your work, as well, On the other hand, for actual value to the species in this situation, let's await a more objective judgement if you don't mind. Going out on a limb, I'd guess this is your swan song and very last bit off influence on the public discourse, but I have been wrong before and certainly will be again.
Agreed. For anyone who has followed Alexandros, this is a deeply disingenuous and unsatisfying response, but it is par for Scott's MO when he throws out his whole rationalist dogma to just go with his gut:
1. Decent steelman review of the opposing side
2. Humorous and sincere response
3. Very detailed review of some individual point with apparent concessions
4. Brief hand waving dismissal of the strongest and most relevant points (in this case the large industry funded studies that used *different protocols* from the studies on IP-protected drugs)
5. Quick, poorly-defended Hail Mary (i.e. parasites, new studies)
6. Non-sequitur conclusion and declaration of victory.
This has been an especially interesting debate because Scott is rhetorically much more effective while Alexandros has been more dutifully rationalist.
First off, I can't say how deeply I appreciate you correcting on the meta-analysis function (which I believe I railed at you about, sorry), if everyone had the guts to correct their math post-factum the world would be a better place.
Personally I still see the problem here being that medicine, using current trial approaches and statistical methodology, can't prove or disprove any intervention really works for anything, it got stuck at penicilin and smallpox vaccines, everything beyond that is a bunch of interesting drugs (some of which you can try, and might work) that have no real clear effect.
You can't study single digit effects on covid because it's either very fuzzy (time to negative PCR-T, symptom reduction style endpoint) or very niche (mortality from a disease that doesn't kill that many people, and almost always kills in conjunction with a host of other morbidities). Nor is this a good thing to study, we should either aim for drugs that work so well the endpoint, drugs should cure things, and we had drugs that cured things. But when they stopped working we redefined the endpoints instead of redefining drugs.
The proof for this is to look at any life expectancy numbers, the US added 8 years since the 1960 (10 if you discount covid), compared to 22 in the 60 years before that point -- in spite of <points at all the problems in the first half of the 20th century> -- We got vaccines for smallpox, hep a & b and polio, we figured out antibitoics --- then the well ran dry, and we've been grasping at straws that one can adjust away with better food or removal of pollutants or sewage.
This kind of debate is the thing that happens when you've given up on hopes of curing disease and moved the marker to 2nd or 3rd degree aggregated statistics.
I have followed this since the start. In many respects, "can't see the wood for the trees" comes to mind. I am pro ivermectin but it is not available to me here in the UK so For prophylaxis I take Multivitamins, C, D3, zinc AND Quercetin as the ionophore. (Mercola Qurcetin articles and other studies show benefit).Got cold like symptoms once in 3 years. Never masked, never tested with PCR so I do not know if I had Covid. However, I now have parosmia so smell and taste ruined. Onion, garlic and certain toiletries are disgusting to me now. Meanwhile, not a hysterical Alex Jones type analysis....
https://21stcenturywire.com/2023/02/01/covid-19-vaccine-a-military-response-to-a-public-health-threat/ covers the framework and mechanism building on Katherine Watt and Sasha Latypova work around the bioweapon. Long but thorough. Far more pressing than a spat about a suppressed Nobel prize winning, cheap, safe and effective molecule that has been around for decades. Remember, EUAs predicated on no treatments available. Dont get me started on HCQ and the murderous Oxford overdosing trial. Dont worry after all is over we can Build Back Better. I mean us, not Schwab, Tedros, Gates, Fink and their cronies.
Lurker here who carries out systematic review and meta-analyses in academia on a daily basis. Publication bias and funnel plots are better described as the study of "small study biases" than "publication bias" (but the original name has stayed and it would be hard to change it right now...).
Publication bias is one of many explanations, but typically the wrong one. The most likely explanation for assymetry is not that studies carried out suddenly dissapear. Instead, this assimmetry is more easily explained more typically related to p-hacking or other QRPs (Questionable research practices), or more generally poor experimental designs.
It is far easier to shift an effect through p-hacking /QRPs/poor experimental designs in a noisy small study and shift a negative result to more positive one, than in a less noisy and bigger one. Hence, the assimetry does not come from not publishing studies, but from tweaking small negative ones into positive and then publishing them.
This is so in general, but even more likely in this case (where it was aligned with conflicts of interest and political motivations). In this regard, the fourth argument (which is the only one specific to these set of studies, and not against funnel plots in general) is basically baseless.
I wrote specifically that I am adopting the frequentist paradigm for the purposes of this debate, since that's what Scott is using, and I can make my point just as well. Of course the over-reliance on p-values is silly, but that's not the core of the issue with Scott's piece.
Cue 37-part series from Alexandros explaining why Scott is Betraying Rationalism by including such a phrase.
I jest, but Alexandros has gotten *so much mileage* out of waging the culture war on this topic. He has worked very hard to frame his stance as simultaneously subversive and indignant. This shouldn't detract from the legitimate research he has collected. But it does predict his response to any high-profile conversation with Scott.
Anything Scott says can and will be used...not exactly against him, but *for* retweets and Substack follows. That does mean against him if and when Alexandros can frame it as punching up.
So I'll be satisfied if this is the end of the line. Scott has engaged, over and over again, with the factual scaffolding of Alexandros' arguments. The 5-10% chance is an adequate conclusion. Let Pascal and Omura wager accordingly.
"Realistically, this project was outside my expertise and competence level."
FWIW I've thought about that piece a lot this last year, and the object-level "worms break science!" point wasn't what most changed my epistemology. The general importance of turning contrarian views over in one's mind dominated my thoughts and how I discussed this with others.
It was a winning item for me in one-on-one discussions with thoughtful people about contrarian ideas, and how such ideas might be wrong in subtle ways that require thorough analysis, and how herding on this stuff has some risks. It provided a great way for me to evangelize about about how politics is the mindkiller without just talking about politics being a mindkiller and wearing everybody out with it.
"C+ for results"... When you're trying to improve on what's out there, you get to grade yourself on a curve relative to baseline, not on whether or not you saw the pure true center of the universe unfiltered. What's your grade relative to the next best take on this topic?
"Realistically, this project was outside my expertise and competence level."
So help me. If you shy away from these sorts of investigations in the future because you think you overreached here then humanity is doomed. If this implies any risk of self-gatekeeping, please ask yourself if we are better off leaving this to the next best available substitute.
Prompt: Please rewrite Yeats' The Center Cannot hold, but make it about Scott Alexander of Astral Codex Ten worrying that he didn't write a good enough essay because it had some errors and overextended a conclusion, when he in fact wrote the most thoughtful essay humanity produced on the topic.
Ha, rereading that poem is so mid and over the top, even for chatgpt, it probably backfires and undermines my point. But it's fine, we're all big dorks deep down and awkward imperfect things are beautiful. Sometimes we can just wabi sabi some shit and it's fine.
Alexandros blocked me on Twitter long ago just for asking whether there was one good RCT supporting ivermectin. He apparently runs a startup, yet has the time in just a few months to write a series of posts that total over 86,000 words (a sizeable non-fiction book!) just to respond to ONE blog post from Scott. And everything he wrote was completely predictable in advance. If a study was pro-ivermectin, he was going to defend the study to the death; but if it was anti-ivermectin, then he was going to nitpick it to death.
That's not why I blocked you. The reason I blocked you is much the same as the reason you were banned 3 times from theMotte subreddit for responding to me with ad hominems and insults.
I won't be entering a debate with you, so feel free to respond in whatever way you like.
The Reddit exchanges came later. At that point, I had become frustrated due to our exchanges over a Marik study where you were clearly in the wrong, but refused to admit it, and I had to laboriously explain to you why it is important to have a constant denominator (and what a "denominator" even is). At that point, I had given up an earlier belief that this was a good faith discussion -- what sort of person pretends not to know what a denominator is (or else just changes the subject)?
Interesting to see that Alexandros' heroes and affiliates are now promoting ivermectin for other infections as well, not because there's any evidence but because of . . .
I think IVM advocates started gaining popularity- with very loud lack of interest from most scientists- before the media started commenting.
"I'm not 100% sure why Strongyloides emerged as the top contender"
From quick noodling around because it's often prevalent in a lot of places, prevalence is unrecognised, it causes a bunch of symptoms that can be mistaken for other things, and medical professionals don't tend to test for it regularly so are unaware if a patient is suffering from an infestation.
https://www.racgp.org.au/afp/2016/january-february/chronic-strongyloidiasis-don-t-look-and-you-won-t
.... university administration, ....
That was hilarious. Thank you for that - made my day.
Short rule of thumb for me. If Alex Jones is on the side of something, it isn't worth even considering. There is too much going on in life
https://www.lesswrong.com/posts/qNZM3EGoE5ZeMdCRt/reversed-stupidity-is-not-intelligence
Have to sort of disagree with EY on this one.
You've got "stupidity" in the sense of a bad world model that produces random conclusions, but then you've also got "stupidity" in the sense that smart people have looked at an idea and think it's dumb. The first one isn't anti-correlated with reality, but the second one definitely is- and there are things that can selectively bias people in favor of that sort of thing. For example, when experts and credible sources disproportionately belong to a political class that you oppose, when you rely for your livelihood on the attention that comes from being contrarian, when you're enamored by the narrative of being a lone voice of truth in a world of illusions, and so on.
Alex Jones ticks enough of those boxes that him taking a stand on a controversial issue is pretty decent evidence that experts take the opposite stand- which is pretty decent evidence that his position is false.
Also, suppose you've already seen some evidence for and against a position, and have a lot of uncertainty about whether it's true. If you unexpectedly discover that there's a prolific and very dumb counter-culture promoting one side of the issue, shouldn't you wonder whether the evidence you've seen was biased by that group's efforts and adjust your credence accordingly? Reversed stupidity may not be intelligence for a blank slate, but if there's any chance you've been influenced by stupid, reversing it by a proportional amount just seems prudent.
I'm surprised Scott didn't link to this instead:
https://slatestarcodex.com/2019/02/04/respectability-cascades/
Scott has better epistemic hygiene than Matt Ball.
"They're turning the frogs gay!" isn't a theory that environmental endocrine disruptors are affecting sexual development in amphibian populations. It's a theory that the US government is using chemical warfare as a form of population control by feminizing men and turning them gay to stop procreation. One of the side effects of this plot is that now most frogs are homosexuals. Suffice it to say, Alex Jones is wrong about this.
Alex Jones was using a bit of pop coverage about a known scientific phenomenon, distorting it, and folding it into a ludicrous conspiracy theory. Being suspicious of Alex Jones endorsed conspiracies doesn't require you to dispute every single detail found in them, however strained.
I don't know. How many? I suspect not a lot. I'm not sure the answer is greater than zero. The causality is oddly inverted here as Jones's conspiracy theories trade on popular media coverage of scientific findings.
What we have is a Scott Alexander anecdote where Scott brings up in polite company that what Alex Jones was talking bout was actually real and feels admonished for this. There's not much we can make of that, though it is notable that what Alex Jones was talking about wasn't real if you actually understand what his whole rant about the frogs being turned gay is about, so there's that.
If you assumed that what Alex Jones says must be wrong, then you'd assume he was wrong about them turning the frogs gay (whether it's a side-effect or regardless of intentionality).
Do you think the person was asserting that if Alex Jones believe it is a good idea to breath air, then Alex Jones must be wrong? I think we're able to give credit to how people colloquially communicate ideas and presume they probably mean that Alex Jones is apt to be on the wrong side of issues controversial issues that aren't conventionally accepted among people with greater credibility. That's usually what people mean when they express something like this.
If the response is, "But he wasn't wrong about the gay frog thing!," then I think it is worth noting that he was, in fact, wrong about that, both in the particulars of the assertion and what theory he was trying to communicate with that. That he loosely based it on a widely covered phenomenon that isn't all that controversial misses the point.
Yes, but let's face it: This is some noise-ass, low-veracity Bayesian evidence, to be fair, and probably shouldn't budge your needle much in one direction or the other.
If you know someone to be a pathological liar, disbelieving everything they say that you can't independently verify is not only a good bet, I would argue it's your ethical duty.
No, it gives that pathological liar an easy means of convincing you of falsehoods.
The key here is that there has to be another "side" in the argument that the pathological liar is diametrically opposed to. If propositions imply that one is false and one is true, you can make safe inferences on the other position based on which side the liar is on.
Obviously most issues aren't that clean, but as a heuristic, it could be a lot worse.
The Nazis were well known for lying. And when they found a bunch of bodies in the Katyn forest and blamed it on the Soviets, the natural assumption would be the Nazis were blaming one of their own numerous massacres on another "side". But they were actually telling the truth in that instance, and your heuristic would repeatedly fail if you assumed the opposite side of a known liar must be a truthteller. It's entirely feasible for two liars to be opposed to each other.
That's the other obvious failure mode of this heuristic, yes. But the majority of people are not outright liars, especially in the scientific community, so it's still useful in this instance and many others. (Also, it should go without saying that no individual failure of a heuristic makes it invalid; the existence of solar eclipses does not make the "dark outside -> it's night time" heuristic useless.)
disbelieving != believing the opposite
This was during the southeast Delta death surge…ivermectin as prescribed in Florida is clearly ineffective:
A recent study examining trends in ivermectin dispensing from outpatient retail pharmacies in the United States during the COVID-19 pandemic showed an increase from an average of 3,600 prescriptions per week at the pre-pandemic baseline (March 16, 2019–March 13, 2020) to a peak of 39,000 prescriptions in the week ending on January 8, 2021.1 Since early July 2021, outpatient ivermectin dispensing has again begun to rapidly increase, reaching more than 88,000 prescriptions in the week ending August 13, 2021. This represents a 24-fold increase from the pre-pandemic baseline. (Figure)
https://emergency.cdc.gov/han/2021/han00449.asp
Unfortunately patient self advocacy is like playing chutes and ladders. Encounter a medical problem for you or your loved one and find out- there's no hand holding
That's literally the same as arguing that eating sugar is bad because Hitler ate sugar. So if Alex Jones said that eating healthy is good then all reasonable people should go eat only fries at McDonalds 3 times a day 7 days a week?
This is a false equivalence, because Alex Jones believes lots of true things he doesn't put on his show. What he chooses to put on his show is filtered for controversy and sensationalism. Nothing he puts on his show will be anything people generally agree is true.
Well if you want to believe everything that people generally agree is true then you can just do that and cut out the Alex Jones involvement.
Believing everything that people generally agree is true is a pretty good strategy in life. You'll be right more often than you're wrong, and when you're wrong then at least you don't lose too many friends over it.
But if you're happy to just follow the believe-what-everyone-else-believes strategy then you needn't waste your time reading rationalist-adjacent blogs like this, which are about the often-quixotic struggle to do ever so slightly better than the general consensus.
Well, I don't think that it's quite this simple these days, as compared to say 70 years ago. To an extent, there are now two mainstreams, the "establishment" and "anti-establishment" ones, to vaguely gesture at their essence. Many reasonable people believe that certain prevalent and high-status expert endorsed narratives are thoroughly wrong or "not even wrong". Arguably, Alex Jones serves a useful role in trawling through the "anti-establishment" thought-space and gathering all of its worst trash in one place. I wonder if there's an "establishment" equivalent.
70 years ago there was also an establishment and an anti-establishment. The anti-establishment included Civil Rights activists, draft-resisters, folk/rock musicians, etc. And, admittedly, lots of wackos.
I think the point is that Alex Jones generally airs the opposite of what people generally agree on, so it's still valuable information, thus you shouldn't cut out people like him. If you want to go for "believe everything people generally agree on", it's a lot less effort to watch AJones and believe the opposite, than to go around and ask everyone about what they believe on those same issues.
Some things are only worth a rough heuristic.
It's not bad as a first approximation. But to then go on and say that a first approximation is all you need and no one should do further analysis, is stupid.
Jones is, in fact, right sometimes, even when he says controversial things. And some things he's wrong about have decent evidence for them.
Whether a drug has massive value against Covid is certainly a question worth more than a rough heuristic.
You're giving Alex Jones a hell of a lot of power over you there.
He seems to be a very powerful person, having caused a gigibucks worth of hurt feelings and all.
A sensitive instrument is one that can pick up and amplify small signals that others miss, and no doubt this "sensitivity" has been an integral part of what has made your writing as successful as it has been. Getting overwhelmed more easily than you might otherwise be is the other side of that tradeoff, and it's great that you're not letting the tough side of that get in the way of giving things the response you know they're due.
Thanks for taking the time to respond to him, even though it hasn't been fun. I doubt I'm the only one that notices and appreciates the effort.
> Dr. Ioannidis is known to be unusually rigorous and this is part of his pro-rigor crusade
I'm not familiar with all his work, but I think he deserves a reputation for self-promotion more than a reputation for rigor. I think his most famous essay is "Why Most Published Research Findings Are False", and I think this paper is notable for its sensational headline much more than for its careful analysis.
https://en.wikipedia.org/wiki/Why_Most_Published_Research_Findings_Are_False#Reception
That's his most famous paper but it's not his most cited.
https://scholar.google.com/citations?user=JiiMY_wAAAAJ&hl=en
He was also involved in this fairly important early paper on COVID seroprevalence
https://pubmed.ncbi.nlm.nih.gov/33615345/
An important but wrong paper on seroprevalence. That really tarnished his reputation.
I took him to ask about that at https://slatestarcodex.com/2013/02/17/90-of-all-claims-about-the-problems-with-medical-studies-are-wrong/ but I do appreciate a lot of his work, and think that at that point he was one of the few people sounding the alarm at all.
The early seroprevalence study had quite a few serious problems - but even worse he used it to generalize from non-representative sampling to wrongly characterize the virulence of COVID by a wide margin.
Also:
https://replicationindex.com/2019/01/15/ioannidis-2005-was-wrong-most-published-research-findings-are-not-false/
And:
It's too perfect that this response to Ioannidis was co-authored by someone (Sander Greenland) who had positive things to say about Alexandros' analysis on Andrew Gelman's blog.
https://journals.plos.org/plosmedicine/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0040168
Fabulous stuff, all of it.
I didn't really have an opinion on Ioannidis before COVID times. But during the pandemic, I got a quite poor impression of him.
He was one of the early figures to warn that COVID might be an overrated problem, especially that mortality might be lower than common estimates, and gave his own, much lower estimates, of the problem. Even then I had the impression that his data looked rather cherry-picked. He dismissed some of the best and cleanest sources from that time, from cruising ships and from Bergamo and other European regions, which would have been more alarming. That data was cleaner than what he took. But this was during the first few weeks of the pandemic, in a chaotic situation, and no data was really good, so that was still kind of ok.
But the real problem was that he didn't update when better studies came out. A year later, he would still stick to his old estimates in public interviews, even though there were much better studies by then, and his estimates were far out of the plausible range. Honestly, it was getting ridiculous.
I know that he deserves big praise for uncovering the replication crisis, but I really think that his performance during COVID was a scientific and Bayesian failure. Perhaps he became hyper-skeptical of studies after the replication crisis (or was so before, which made him detect it). But the issue is that he didn't just concluded "We don't know", but that he concluded "We don't know, so don't take the estimates from the literature, but take my own even more fishy estimates instead." And sticked with that.
I agree the pandemic was not his best moment.
Ah, interesting. I've never read SBM before but there's a pretty extensive criticism here
https://sciencebasedmedicine.org/what-the-heck-happened-to-john-ioannidis/
Wow, thanks for sharing! I didn't know that it was so bad.
It's sad that such a brilliant mind can be trapped in some believe and totally disconnect from evidence about it. There are quite a few tragic cases like this, like physicist Roger Penrose or mathematician Michael Atiyah. Ioannidis is not there yet, but he might be heading that way.
I'm not necessarily saying I agree with all of the criticism, just surprised to find it all in a neat little package here.
I didn't really follow what Ioannides did, he isn't a public figure here in Europe. For example, I didn't know about his attacks on the PhD student.
But I noticed some bits, especially in March 2020, and later sporadically when he gave interviews to the news here, and my impression is pretty consistent with the article. It's just that the article contains a lot more of the same stuff.
When you refer to the tragic case of Robert Penrose, what do you have in mind? His theory of Conformal Cyclic Cosmology, or something else?
I was rather thinking of his concept of consciousness. He started with the idea that consciousness can impossibly be restricted by Gödel's incompleteness theorem, and thus computers can never become conscious. In more elaborate versions he insists that consciousness is impossible without resorting to quantum gravity effects in the brain. All this is completely detached from any evidence (in fact, there is lots of evidence against it) except for his gut feeling of what properties consciousness should have.
I think the Penrose and Atiyah cases are somewhat different.
Penrose started going publicly off the rails about Consciousness And All That with "The Emperor's New Mind", published in 1989 when he was 58 and still (so far as I can tell) a genuinely brilliant mind.
Atiyah started going off the rails in his late 80s, when he was fairly clearly losing his mind. This wasn't a matter of a brilliant mathematician/physicist getting taken in by a bad idea, it was a matter of a _formerly_ brilliant mathematician/physicist no longer being able to tell good ideas from bad ones. A very different kind of tragedy.
Fair point.
"He dismissed some of the best and cleanest sources from that time, from cruising ships and from Bergamo and other European regions"
This has probably been argued elsewhere, but cruise ship passengers tend to be older and fatter than the general population. Italy also has a lot of old people.
The sources may be clean from the point of view that the populations are isolated, but they aren't representative in other ways.
True, and these things need to be accounted for. But this is possible and should be done, and the data should not be completely thrown out of the window. In the Bergamo region with about 1,000,000 people, the number of deaths in March 2020 was six times as high as in a normal month. So this March had half as many deaths as otherwise a whole year! Of course, this can become a bit less worse at other places if you adjust for age.
But Ioannidis arrived at the prediction:
"If we had not known about a new virus out there, and had not checked individuals with PCR tests, the number of total deaths due to “influenza-like illness” would not seem unusual this year. At most, we might have casually noted that flu this season seems to be a bit worse than average. The media coverage would have been less than for an NBA game between the two most indifferent teams."
Granted, this was mid-March 2020, but at this time preliminary death numbers from (smaller) parts of Bergamo were already available. There was just no way to arrive at his conclusion by "adjusting for age". Still, if he had corrected his estimates one or two months later, that would have been fine. But he sticked to them (and actively propagated them) long after the point where they were simply ridiculous.
The general population isn't the primary comparison due to age. The cruise ship data WERE controlled by age - but they didn't control for factors like SES - which I think would likely make cruise passengers HEALTHIER (more active, better baseline health, more access to care, etc.) than their age-matched peers
I had been quite a fan of Ioannidis.
As such, I was shocked when, early on in the pandemic, he extrapolated a generalized IFR from the Santa Clara seroprevalence study without any post stratification for such factors as SES or race/ethnicity. It's a fundamental mistake of science to extrapolate from non-representative sampling in that way. Here's a good interrogation of the poor epidemiological science in that study (from an UCSF Grand Rounds talk):
https://youtu.be/NTXgbN6uB1I
And that's on top of the ethical violations in that study (recruitment telling people they'd get an "immunity passport" if they tested positive without telling them of false positives - at least one co-author quit the study over that) and other dubious aspects like recruiting through personal emails from the wife of one of the authors. And that's all on top of the questionable statistical methodology:
https://statmodeling.stat.columbia.edu/2020/04/30/updated-santa-clara-study-of-coronavirus-infection/
Based on that fundamentally flawed science he went on a national TV campaign where he significantly underestimated the virulence of COVID - likening it to the seasonal flu.
OK, everyone made mistakes with COVID - but the fundamental scientific flaws underlying the mechanisms of his errors were shockingly bad for an epidemiologist of his stature.
And then he has the gall to complain about the politicization of the science during the pandemic - which of course IS a HUGE problem but he contributed significantly to that problem.
I'm repeating this comment because it appeared to get truncated above? (I'm not familiar with this comment interface)
I had been quite a fan of Ioannidis.
As such, I was shocked when, early on in the pandemic, he extrapolated a generalized IFR from the Santa Clara seroprevalence study without any post stratification for such factors as SES or race/ethnicity. It's a fundamental mistake of science to extrapolate from non-representative sampling in that way. Here's a good interrogation of the poor epidemiological science in that study (from an UCSF Grand Rounds talk):
https://youtu.be/NTXgbN6uB1I
And that's on top of the ethical violations in that study (recruitment telling people they'd get an "immunity passport" if they tested positive without telling them of false positives - at least one co-author quit the study over that) and other dubious aspects like recruiting through personal emails from the wife of one of the authors. And that's all on top of the questionable statistical methodology:
https://statmodeling.stat.columbia.edu/2020/04/30/updated-santa-clara-study-of-coronavirus-infection/
Based on that fundamentally flawed science he went on a national TV campaign where he significantly underestimated the virulence of COVID - likening it to the seasonal flu.
OK, everyone made mistakes with COVID - but the fundamental scientific flaws underlying the mechanisms of his errors were shockingly bad for an epidemiologist of his stature.
And then he has the gall to complain about the politicization of the science during the pandemic - which of course IS a HUGE problem but he contributed significantly to that problem.
typo: contraian
this (thankfully) isn't a typical post, but the extremely detailed, technical analysis of a minor current thing from 2 years ago is peak ACX energy
This is still a major topic and will continue to be a major topic as long Covid generates millions of disabled ppl
pedantic typo patrol: "...equal number of studies on both size."
Thanks, fixed.
We have done an intensive study of viral load dynamics in our phase 2 platform trial. Ivermectin got dropped pretty quickly (pre-specified futility rule was met). In contrast, known effective antivirals such as casirivimab/imdevimab and remdesivir showed an effect on viral load dynamics pretty quickly.
https://www.medrxiv.org/content/10.1101/2022.07.15.22277570v1
https://www.medrxiv.org/content/10.1101/2022.10.17.22281161v1
Alexandros blocked me on Twitter long ago just for repeatedly asking whether there was one good RCT supporting ivermectin. He apparently runs a startup, yet has the time to write a series of posts that literally total over 86,000 words (a sizeable non-fiction book!) just to respond to ONE blog post from Scott. And he did this over the space of a few months.
In other words, he has been engaged in a 24/7 side hustle--writing a full non-fiction book in a few months -- and moreover, it was all on a very narrow question about whether one particular blogger was mean about a particular drug that supposedly is a miracle cure for Covid (even though no rigorous study has ever shown that). Odd choice of priorities.
And despite aiming towards rationality, he is keen to write thousands of words nitpicking at the tiniest flaws in any negative ivermectin study, even while defending much worse studies or websites that defend ivermectin. Blatant double standard.
PS, when I spent 5 minutes pasting Alexandros' blog posts into Microsoft Word, the result is 291 pages long (single spaced). Even if someone was unemployed, who has the energy for that kind of monomania?
I do if it's called "Playing Civilization VI"
Why not play a better one? Blegh.
If he doesn't have two toddlers I can say from experience where that time might come from
I think it's probably bad to make fun of people for spending too much time obsessively trying to get things right, even if you think they failed.
I'd agree. But given the double standard (which you repeatedly and correctly note), he is not "trying to get things right." He's trying to defend ivermectin at all costs -- he comes up with the smallest nitpicks at any study showing that ivermectin doesn't work, while defending much lower-quality pro-ivermectin studies on the grounds that "but there's a STAT article" or "but this guy won a science competition" or some similarly one-sided argument.
Okay, so what we're generally implying when we accuse somebody of having 'double standards' is that they're deliberately misinterpreting data. But when you're dealing with this much data, and a discourse that spans months, asymmetries in your application of epistemic rigor are bound to emerge.
In my submission, this doesn't really confirm a deliberate misinterpretation of the data. Scott does a reasonably good job being generous about that here.
Yeah, especially since many here, including me, are prone to doing exactly that. And besides, I'm not sure it's a bad trait. It makes life harder for the person who has it, but it probably also makes them likelier to obsessively try to get something right, and succeed at doing so.
To be clear, it's not bad to obsess over getting something right. But I think it's to obsess over defending a predetermined position at all costs (have you read my friend Julia Galef's book on the scout mindset?)
Scott, I admire you for following through on writing this. My guess is that holding yourself to your pledged sucked, but you did it because you'd said you would, and also because you felt bad about some errors of yours Alexandros had pointed out. Jeez, write something you enjoy the hell out of next.
I absolutely hate this kind of thing. Alexandros can invest his time however he likes. And blocking people for repeatedly tweeting the same thing at you is generally reasonable behavior.
Yes, he can indeed invest his time in eminently ridiculous ways. Up to him. But it is still subject to ridicule by other people who are interested in what's actually true. If he were actually interested in truth, he wouldn't have such a double standard that accepts and defends the fringe-iest evidence for ivermectin while ridiculing and often blocking anyone who asks for more rigorous evidence.
I expect Scott put way more time into writing this response than he wanted to. In fact my guess is that working on it SUCKED, and that he held himself to doing so anyway because he said he would, and also because he felt bad about so genuine mistakes that Alexandros pointed out. Want to make fun of Scott's obsessiveness too?
"If he were actually interested in truth, he wouldn't have such a double standard that accepts and defends the fringe-iest evidence for ivermectin while ridiculing and often blocking anyone who asks for more rigorous evidence."
Also, the thing none of us know about Alexandros is why he's persisting. Is he so invested in being Ivermectin Man that he can't allow himself to see how bad the case for it is? (That's my theory.) Does he know so little about research he can't tell good from bad? Does he know the evidence for Ivermectin's terrible, but he's cynically pretending it is not because he's profiting from being an advocate for the drug? But you're not addressing that question -- just throwing rotten eggs at him.
Could be any or all of the above, but the thing is that even by you, there is no reasonable explanation. All of them are bad for Alexandros. So why are you so eager to keep weighing in on behalf of someone for whom there is no possible rational defense?
Because I think that laughing at someone who's been bested is meanspirited. If the mockery is mixed with new information or a new take on what happens, then I experience it differently -- then it's an angry, substantive comment.
Because I think that laughing at someone for making a lot of effort trying to get to what they think is the truth is incredibly toxic for everyone.
But we don't have to pretend that everyone is trying to get at the truth. Alexandros is applying an absurd double standard whereby any negative ivermectin study has to be scrutinized for every tiny flaw whereas pro-ivermectin studies will be excused for far greater flaws.
There is plenty of room for good faith people to engage in discussions without always being derailed by the impulse to give the benefit of the doubt to people who don't deserve it.
PS, I didn't repeatedly tweet the same thing at all. Here's how it ended. If someone had good evidence on their side, why wouldn't they cite it rather than blocking me? https://substackcdn.com/image/fetch/w_1456,c_limit,f_webp,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Ff08ee13f-d59f-4ffa-82af-1bb6e6b9685a_550x787.png
Look, I'm no fan of Alexandros but I don't think you really score any points against him here. Why would he block you on Twitter for repeatedly asking whether there is one good RCT supporting Ivermectin? He thinks there are multiple good RCT's, doesn't he? Seems more likely that he pointed to studies that he considered good RCT's, you said, "no they're not because . . ." and he got tired of arguing with you.
Why does writing a full non-fiction book while running a start-up suggest that he or the contents of his book are not to be trusted? Maybe he's got lots of energy -- or maybe he's bad at time management -- or maybe he's just overinvested in winning the argument with Scott, even though the practical consequences of his winning or losing are small. All these possible personal failing of his seems kind of irrelevant in the context of a discussion of whether he's right about ivermectin, or whether he's arguing in good faith.
As for his nitpicking flaws in studies that don't support Ivermectin's efficacy, and his defending bad studies that do -- well, he would say that the flaws he's picking aren't nits, they're big, and the studies he's defending are not bad. I think he probably believes that.
Nonsense. In my exchange with him, he never pointed to even one good study. Here's how it ended:
https://substackcdn.com/image/fetch/w_1456,c_limit,f_webp,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Ff08ee13f-d59f-4ffa-82af-1bb6e6b9685a_550x787.png
If you had multiple exchanges with him, there's no way I'm going to dig through the manure pile of Twitter for them. I did read the exchange you linked, and it's not clear what his view is about good RCT's existing. He once says "no good RCT's" but I don't know what he means -- is it agreement? a sarcastic gibe? If he really thought there were none, I'd expect him to say something like, "yes, OK, all the studies are imperfect, still if you look at the mass of evidence blah blah. . ." Then later he says something like "nothing would convince you." That could mean he's pointed to what he thinks are good RCT's and you dismiss them as not, or I suppose it could mean something else. So this exchange with Alexandros is far from solid evidence that he doesn't believe there are good RCTs. Actually, it's sort of like the case for Ivermectin's efficacy -- you can point to it as evidence for your view, but in fact it's full of holes.
Look, I hope it's clear that I do not think Ivermectin is useful against covid. I just don't like the way you're making fun of Alexandros. I get that he annoys the hell out of you, but if you want to go after him make good points, don't just snigger,
No, he never pointed to even one good RCT. Earlier in the discussion, he pointed to ivmmeta.com (not a trustworthy website) and the Bryant meta-analysis (also not reliable because it included fraudulent studies). That's all he had.
But say, why are you trying to reconstruct Twitter history from 2021 to critique me on the grounds that Alexandros MIGHT have said something defensible back then? Why do you care so much, such that you're inventing alternative histories in which he had good RCTs to cite (which he didn't)? Why bend over backwards to give every possible benefit of the doubt to him rather than to me?
Because you're the one trying desperately to defend a pointless smear, I'd wager.
"As for his nitpicking flaws in studies that don't support Ivermectin's efficacy, and his defending bad studies that do -- well, he would say that the flaws he's picking aren't nits, they're big, and the studies he's defending are not bad. "
If he thinks that, he doesn't know what he's talking about, because it is objectively wrong. For example, the TOGETHER trial is not objectively worse than the Borody study -- quite the contrary.
Hey, I agree that the case for Ivermectin is bad and the case against it is good. It's just not clear what point you're making about Alexandros by saying he's very critical of good studies and goes easy on bad ones. We're all aware of the thing you keep pointing to -- yep, ridiculously hypercritical of studies that weight against Ivermectin. And?
|or maybe he's just overinvested in winning the argument with Scott
I'll note that Alexandros was clearly expending massive amounts of time and effort on ivermectin advocacy before Scott wrote anything on the subject.
To give the other side of this thing, his company has produced this: <https://www.balena.io/etcher>, which is a really nice way to flash USBs and which has saved me a bunch of time in the past.
Wait, really? Hilarious. I have to use that to create Homebridge images for my smart home setup.
Well, no. He's writing on a controversial topic that inspires fervent support amongst true believers. His comments show he's clearly attracted an audience, and he's baited Scott, who has a huge audience, into writing a long post in response. So whatever else he has done, his efforts have won him a big audience that he can than parlay into either a platform for his ideas or into some kind of monetary profit. You are being rather uncharitable to assume he did all over an obsessive need to prove Scott wrong.
If you disagree with what he writes, please attack the writing directly, rather than "it is wrong to have a hobby while running a startup".
If Alexandros had been right, that time would've been extremely well-spent. It's not like he spent any of your money on it.
Scott's original post had so much stuff in it that if it was on any other subject we would have called it a Gish Gallop. It's unsurprising that responding to everything in it would take such a huge number of words.
I don't think that's fair. The characteristic of a Gish gallop is that one throws out a large number of basically-independent claims without providing justification for any of them, taking advantage of the facts that (1) one can _state_ something much more quickly than _refuting_ it and (2) if you merely state something and someone else merely denies it, then to most people it looks as if you're in the right and they're in the wrong.
Scott's ivermectin post wasn't like that. It's mostly long because it's looking at a large number of studies, which ivmmeta can simply list in a big table but Scott had to look at in at least a paragraph's worth of detail.
Scott's post was the _exact opposite_ of a Gish gallop: it was very long because it was responding to something else that was long but didn't go into details.
(Maybe you could argue that he should have looked in _more_ detail at some of the studies. That would almost certainly have made his post longer, not shorter.)
The important trait here is not how much detail it has, but that it has many arguments that would take a lot of time and space to respond to--so much that most people would give up because of the volume, regardless of whether the arguments have merit.
Complaining about Alexandros using a huge number of words to respond to Scott isn't fair; Scott said so much that in order to respond fully, he *had* to use a huge number of words.
I agree that complaining about the length of AM's response to SA is likely unreasonable. (It depends on what that length actually consists of; I haven't looked myself.)
What I'm objecting to is something more specific: "if it was on any other subject we would have called it a Gish gallop". I hope we wouldn't, because "Gish gallop" doesn't just mean "very long thing", it means a particular _kind_ of very long thing, and Scott's post was unambiguously not that kind of very long thing.
This analysis is great but I'd like to pay more attention to what our prior should be that some existing medication has a substantial benefit in treating a new disease when there isn't a strong theoretical basis supporting that use. My sense is that our prior should be very low. I mean, just ask yourself how much you'd be willing to bet about a large rigorous study showing a 10% drop in deaths from a random drug.
All the argument as to what direction the studies on ivermectin point is great and all, but even in the best case the evidence isn't very strong. I mean, it's not unusual in the slightest in medicine to see some initially suggestive studies only for the effect to turn out to be a mirage.
So while I think pinning down just how much evidence we have for ivermectin is important insofar as it should inform us whether to bother investing in yet more studies the idea that this should be enough to convince you to take the bet against the strongly theoretically supported side-effects (plus a reasonable prior that many drugs have them) seems like a big stretch.
I agree. On the other hand, one thing Ivermectin has going for it is that it's cheap, easily accessible (and probably quick to make) and well-tolerated. And there weren't many other drugs that were: fluvoxamine and metformin were the only ones I heard about (and actually I don't know whether metformin is cheap or well-tolerated) .It would have been a great thing for the world if some drug like Ivermectin that did give some survival benefit, even a small one, had been discovered. The drug we finally came up with, Paxlovid, is highly effective for unvaccinated people, but it took a long time to develop, is not cheap, not easily accessible, and so unpleasant to take that many people bail before finishing the full course of medication. So I can see giving things like Ivermectin the benefit of the doubt in early research -- though I agree that the pro-Ivermectin people kept going long after it was time to give up.
"and actually I don't know whether metformin is cheap or well-tolerated"
Reasonably so, there are generics of it available. Well-tolerated - the worst side effects are gastrointestinal and usually calm down in a couple of days (though some people get it worse and can't stay on it).
I've been taking metformin for several years now for Type II diabetes and it didn't stop me contracting Covid. Anecdotes are not data, but that is my lived experience 😁
If it does anything it's not prevention of illness, it's improving outcomes. A number of studies found it reduces chance of ER visits and hospitalization, but some did not. Pros and cons are easy to find via google. Current official US guidelines are to not prescribe it for people with covid. A couple of the docs on medical Twitter whom I respect think that's a bad recommendation because metformin's way better than nothing. It's certainly not as helpful as Paxlovid, but Paxlovid's expensive and soon a lot of poor folks in the US will not have insurance that will allow them to get Paxlovid. Metformin was also available when Covid began. Paxlovid was ready to use about a year later, but the supply was limited for a while so it was 18 mos. until it was available for all. And of course Metformin could be used in parts of the world where nobody gets Paxlovid. Here are a couple of studies with positive findings:
https://www.nature.com/articles/s41598-022-09639-2
https://www.news-medical.net/news/20230111/Review-shows-metformin-usage-to-be-associated-with-better-COVID-19-outcomes.aspx
Who knows, maybe it reduced your illness severity.
"Who knows, maybe it reduced your illness severity."
Hard to say, I had a murderous cough (so bad that once I nearly fainted from coughing so hard and not being able to catch my breath). Another family member had no cough but constant vomiting to the point of becoming severely dehydrated (couldn't even keep water down, anything they consumed came right back up). Two other family members just breezed through it like a bad cold.
Especialy when it come to viral disease. There are very, very few effective antiviral drugs, and those that do exist and work are usually the results of a very long trail of arduous and expensive research.
The reason is completely obvious: bacteria have their own biochemistry, thousands of chemical reactions unique to them, which human cells do not use, and which are potential targets for chemical warfare. That's why there are tons of antiobiotics, and lots of compounds, both natural and artificial, show anti-bacterial properties. Viruses don't have any biochemistry at all, because they're not alive. They have *no* chemical reactions unique to them. An effective antiviral needs to interfere delicately but effectively in the chemistry of the invaded human cell, so that it blocks viral entry or reproduction -- which is carried out by human cell reactions -- but doesn't do bad things to the cell.
It's a miracle this is even possible at all, so delicate is the balance to be struck. So the baseline assumption about suggestions that any drug or herbal supplement or whatever is effective that *isn't* the result of some brain-straining enormous expensive effort should be skepticism bordering on incredulity.
But drugs can help in other ways besides being antivirals My understanding is that metformin's mode of action (assuming it really does help covid patients) doesn't involve blocking viral entry or reproduction, but instead mitigating some of the effects downstream from that, eg cytokine storms. This article talks about that: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154087/
Of course such drugs are much harder to find -- seems almost a matter of luck. If you're looking for a covid antiviral you can just throw a drug in with some pseudovirus and see how well the drug blocks the virus. There's no simple way to find out which of the many drugs in use that do not qualify as antivirals slow down the processes by which covid does a lot of damage in those who are infected. In fact I have no idea how metformin was identified as possibly helpful. Nobody seems to be touting it as an antiviral.
Sure. Supportive care is still all we've got in many cases, but it rarely changes outcomes in the kind of miraculous reversal way that you get with antibiotics and bubonic plague, say. It can't, because it's not getting at the root of the problem. I mean...if some people are going to go into full tinfoil-hat frenzy because Big Medicine is pooh-poohing folk remedy X that reduces the severity of symptoms or duration of disease by 15% it's just more of the shouting at the clouds that makes me think watching birds in the feeder in my backyard is a more productive use of my time than the Internet.
But who's going into full tinfoil hat frenzy over this? Since I'm the only person in this discussion speaking up in favor of metformin & similar, it does feel a bit like you're talking about my view. I hope it's clear that I'm not even sure metformin works -- some think if does not. My point, made before you entered the discussion, was that having some cheap, widely available, well-tolerated drug would have made a lot of difference early on in the pandemic (which was when some, including Scott, were talking about fluvoxamine and metformin as a possible drug of that type). Something that at present does nothing more for a covid sufferer than shorten the illness a bit would have made a lot more difference than that early in the pandemic, when few people had immunity, there was no vax and there were no antivirals. And of course in some parts of the world there is still is little or no vax and no antivirals.
And the study I linked to did find considerably more benefit than a 15% redux in symptoms or duration. There was a substantial difference in death rate between metformin users and nonusers.
I must admit that I scrolled straight to the conclusions, and even that felt like a strain at this stage of the ivermectin conversation. The graph of likely false positive results at the end of the post was quite interesting, and I admire Scott's dedication to this topic. Otherwise, I'm hoping we can all move on to other topics!
I guess that Scott wrote this in large part because there's a bigger and always relevant meta-topic of what to belive in the absence of "settled science", and how easy it is to make the mistake of thinking that you've gleaned a valuable insight from the messy landscape.
You seem to be missing the positive results in the MedinCell trial and the new paper on hemagglutination showing that IVM both prevents and reverses RBC clotting associated with poor outcomes.
This was primarily about the studies we discussed in 2021, with me only mentioning a few especially large and well-done studies since then. Still, those seem interesting - can you give me links to those studies?
Here’s the clotting study:
https://www.mdpi.com/1422-0067/23/24/15480?fbclid=IwAR1y7zJLXfZ-apZN_Y9m7UX8ehzUf_pbnCNkYpYzvDDNiW3_kfFmxE7UkwE
The MedinCell trial doesn’t appear to be published yet so it can’t carry much weight at this point, but worth keeping an eye on:
https://www.wsj.com/articles/medincell-announces-positive-results-for-the-saive-clinical-study-in-prevention-of-covid-19-infection-in-a-contact-based-population-01672949585
Yeah, Bret Weinstein did a video on those results recently. I thought Scott's original article was a net win for Team Ivermectin in any case- even being right for the wrong reasons makes a case for having a public debate.
That MedinCell trial also seems very fishy on its face. It randomized 399 people to ivermectin or placebo, and measured how many got infected with Covid in 28 days. https://www.medincell.com/wp-content/uploads/2023/01/PR-results-TTG-VF-EN.pdf In the placebo group, they claim that 105 out of 199 people got a Covid infection in 28 days. Really? Unless this was a challenge trial, it is hard to imagine that over half of people came down with Covid in a 4-week period.
I'd totally believe those numbers if they'd come from, say, China last December.
MedinCell says they did the study in Bulgaria "between March and November 2022"; I don't know about infection rates there, so off the top of my head I'd say it's questionable but not totally unbelievable.
Never mind, I missed a line showing that they were studying people who had been close contact with an infected person in the prior 5 days.
I agree with these conclusions a lot more than those from your original post.
One quibble: what does "clinically significant effects" mean? Is the burden "better than a placebo"? "Better than Paxlovid"? "Better than no placebo"? The differences in efficacy between those thresholds are large enough to drive a truck through.
I originally framed it as d > 0.3, but as mentioned in the quote in 7B, Alexandros preferred to talk about a 10%+ drop in mortality for high-risk patients.
I think there might be a typo in the phrase "not for excess mortality in the control group" in the Cadegiani et al section
If they were hypothetically going to condemn him for giving unhelpful drugs to people, wouldn't that involve them complaining about excess mortality in the treatment group, not the control group?
Outside of the technical arguments, you deserve credit for taking the high road in responding to Alexandros.
If nothing else, his bad faith characterizations of you made it clear that he's not very strictly bound by the available evidence. No one is perfectly in control all the time, especially when there's strong disagreement - but getting as far out over his skis as he did in impugning your motivations is a strong tell for "motivated reasoning." Unless he's got mind-reading skills which he hasn't yet explicated.
But the bottom line is that accountability is the key - and you've demonstrated accountability here.
I don't think he was especially bad faith. I accused him of being bad in a few ways, he accused me of being bad in a few ways, we mostly disagree with each other, but this seems within the normal range.
Maybe - but normal range is a pretty low standard, imo.
I'm not going to go back and look and I could be wrong, but my recollection was that there was a difference in that he explicitly attributed conscious mal-intent and impugned your motivations in ways that required mind-probing, whereas you (perhaps foolishly) observed on sub-optimal behavior.
I see a distinction there as the one set of actions is unnecessary and counterproductive, whereas the other reflects fallacious (or motivated) reasoning.
That might seem like semantics but as an observer, for me it reflects a meaningful category difference. Of course, we can and do all cross that line at times; the question then becomes about frequency and more importantly accountability.
On accountability, I recall trying to engage with him on the fallaciousness of his process of attributing motivation and intent on your part, and him being totally unaccountable/unreflective
It would be interesting to go back and see if my characterization of my exchange with him isn't correct, as that would reveal a form of bias on my part. But it would be take too long a time to find it.
I think not so much Alexandros as his fanboys, who kept popping up here to pester Scott about "why haven't you answered Alexandros yet, huh? huh? have you read this new study, huh? huh? why won't you admit you were wrong and he was right, huh? huh?"
They annoyed me, anyway.
You thought he was not engaging in good faith and was dishonest, at least at first. But yeah, the normal range is wide
I doubt Ivermectin works, happy to be convinced with stronger evidence.
What I found most alarming was how politicized Ivermectin became, most glaringly with the CDC, pretending as if Ivermectin was only for livestock with their infamous "you are not a horse" tweet [1] which may (?) have encouraged people like Dr Jason McElyea to make up fictitious stories about people "clogging up hospital beds because they are OD'ing on Ivermectin" [2]
Meanwhile, the CDC suggests ivermectin off-label to treat lice, even though there are plenty of FDA approved OTC and prescription treatments [3]. I quote:
"Given as a tablet in mass drug administrations, oral ivermectin has been used extensively and safely for over two decades in many countries to treat filarial worm infections. Although not FDA-approved for the treatment of lice, ivermectin tablets given in a single oral dose of 200 micrograms/kg or 400 micrograms/kg repeated in 9-10 days has been shown effective against head lice"
_____
[1] https://twitter.com/us_fda/status/1429050070243192839
[2] https://reason.com/2021/09/06/ivermectin-overdoses-oklahoma-hospitals-rolling-stone-hoax/
[3] https://www.cdc.gov/parasites/lice/head/treatment.html
Also scabies, especially in parts of the world where the first-line treatment, permethrin, is not easily available.
I think it should probably have been made available over the counter, instead of being heavily suppressed. At the very least that wouldn't have fed the fire of conspiracy theories as much, and it's probably safer for people who want to take it not to have to rely on veterinary or questionable sources.
I’ve always leaned towards explaining Ivermectin’s apparent success in the developing world as a case of a low-resource medical team throwing everything they got free from WHO at a novel infection, which then got written up as, “My 20yo cousin got broad-spectrum antivirals AND Ivermectin and lived….my 80yo uncle only got the antivirals and died…must have been the Ivermectin,” with a small side order of parasite load.
A lot of the stories in 2020 were of the, “We really don’t know much…here’s a handful of straws to clutch at…” variety.
Exactly. With the survival rate between 99 and 99.9 for people under 50, it's difficult to separate placebo from cure without large scale double blind RCT, then replicate those RCTs.
What was so sad the last 3 years was how political ideology dictated which were the favorable placebos, which allowed absolutely terrible studies to get praised. Case in point, consider "Lifting Universal Masking in Schools — Covid-19 Incidence among Students and Staff" which somehow made it into NEJM to promote cloth masking toddlers.
I think part of the problem also was the various 'miracle cures' were being peddled alongside "don't get vaccinated, take this instead" like Dr. Cadegiani and his co-authors:
Lucy Kerris is a paid consultant for both Vitamedic, an ivermectin manufacturer, and is co-founder, as well as acting as a paid consultant, for Médicos Pela Vida (MPV), an organization that promotes ivermectin as a treatment for COVID-19 and discourages COVID-19 vaccination.
Flavio A. Cadegiani was a paid consultant (USD 1,600.00) for Vitamedic, an ivermectin manufacturer. Dr. Cadegiani is a founding member of the Front Line COVID-19 Critical Care Alliance (FLCCC), an organization that promotes ivermectin as a treatment for COVID-19.
Pierre Kory is the President and Chief Medical Officer of the Front Line COVID-19 Critical Care Alliance (FLCCC), an organization that promotes ivermectin as a treatment for COVID-19 and discourages COVID-19 vaccination. Dr. Kory reports receiving payments from FLCCC. In February of 2022, Dr. Kory opened a private telehealth fee-based service to evaluate and treat patients with acute COVID, long-haul COVID, and post-vaccination syndromes. Dr. Kory expresses personal points of view against COVID-19 vaccination.
Jennifer A. Hibberd is a co-founder of the Canadian Covid Care Alliance and World Council for Health, both of which discourage vaccination and encourage ivermectin as a treatment for COVID-19.
Juan J. Chamie-Quintero is a contributor to the Front Line COVID-19 Critical Care Alliance (FLCCC), lists the FLCCC as his employer on his LinkedIn page, and expresses personal points of view against COVID-19 vaccination."
So whatever the virtues of ivermectin (which remain to be proven re: covid), the publicising of it as a cure was being done with a side of "vaccines bad, don't trust Big Pharma, don't trust the authorities!" which is not going to make the authorities trying to grapple with a new pandemic trust your take or look favourably on your miracle cure, hence the "it's horse paste".
Especially if people were going on Youtube with 'hacks' about "if your doctor won't prescribe it for you, buy it off veterinary stores" which is risky enough - maybe ivermectin won't do you harm, but in general don't take animal medicines, stick with human formulations. For animals (rat studies in this case, but warnings for dogs as well on another site):
"Dominant clinical symptoms of adverse effects and toxicity of ivermectin in animals are tremor, ataxia, CNS depression and coma which often results in mortality."
Okay, that's overdosing, but someone taking medications made for (yes) horses might indeed overdose as well.
Fantastic comment with some background on these people I wasn't even aware of.
The ones who work for ivermectin manufacturers do seem suspect, but aren't you (ahem) putting the cart before the horse on the FLCCC (and similar) people?
They *formed* these organizations in response to their impressions that ivermectin was super-helpful in treating Covid, and in opposition to people promoting vaccines *because they thought ivermectin works*.
While they may be factually wrong in this, if they were correct then agitating for ivermectin and making it easier for people to get would be morally admirable, if not imperative.
I don't know much about most of these people, but Kory in particular is a long-time ICU doctor with a pretty impressive research background -- I can't see how the grift would be worth the squeeze for somebody like that.
Considering the sums of Money big pharma slings around that 1600$ consulting fee sounds laughable. Especially considering the risk a lot of these people took going against the FDA/CDC and a lot of the mainstream. If they are financially motivated they are pretty stupid about it.
Yeah, the CDC definitely lost a lot of respect in my eyes over the past couple years. Utterly shameful behavior on several fronts. -.-
I think many engineers would quibble with the characterization of Elon Musk as an engineer, let alone a brilliant one. He does seem to have had a knack for a) picking investments in engineering companies to buy* or start, and b) hiring good engineers to work for him. But those are not engineering.
* One of his main mistakes with Twitter seems to be his belief that it's an engineering company, rather than a media company.
I'm not sure where I saw it, maybe I can dig it up, but I saw a pretty good round up for sources that basically all said "No, Elon really was the head engineer - or at least one of the top ones - at SpaceX."
I'm not a huge Musk fan, but I think a lot of people are overcorrecting wrt to his competence.
I would like to see those sources. Musk has no formal engineering education, and from what I've seen so far, he shows no appreciation of how absurd (or at least absurdly difficult) many of the things he promises are. The vibe I'm getting is much more "this sounds good, let's sell it and let my dudes figure out how to implement it" than "I have a genius solution to a really hard problem, here is why we can do what no one else can".
I think this is the list I'm thinking of: https://www.reddit.com/r/SpaceXLounge/comments/k1e0ta/evidence_that_musk_is_the_chief_engineer_of_spacex
I'm sure that subreddit isn't exactly unbiased, but it seems a pretty solid list including a decent section of non-employees.
Thanks.
That is surprising, and at odds with everything I've heard about the man in the last years.
FWIW, before he was such a public figure, I read a lot of people claiming first-hand knowledge that he's a brilliant engineer and was indeed responsible for a lot of rocket science at SpaceX. I have no sources or whatever, so take it for what it's worth.
I'm not surprised it's at odds with what you've heard, lots of people in media love to hate on Musk, probably because Musk comes across as self-important and self-aggrandizing in many ways. I think only time will tell for sure.
My mental model of the guy isn't some charismatic business guy who "LARPs as an engineer", (to borrow eleventhkeys terminology), but that he's actually more of a dubiously charismatic engineer who ended up running large businesses, and frankly has a certain amount of distain and disinterest in the business side of things.
This is at least part of the impression I got from him when he came on Dan Carlin's Hardcore History Addendum feed last year - he doesn't come across as particularly charismatic but spends a lot of the time "nerding out" about the technical details of WWII fighter jets.
I don't deny there's certain some level of intentional hype-building in his process, but it's hard for me to judge how much, and overall his track record on technical stuff seems pretty good? (SpaceX, EVs, and Starlink all seem like fairly clear 'wins') Maybe I'm just not familiar with some of the 'absurd promises' he's made? (He's definitely proven over-optimistic about self-driving timeline)
My mental model is that he's a brilliant manipulator and neither a good engineer nor a good businessman per se, but very good at pretending to be both - good enough to fail upward far enough that it becomes difficult to doubt his capabilities.
Regarding the absurd promises, here are a few:
- the Hyperloop
- the Loop (digging lots of tunnels for battery-powered pods to "solve traffic")
- rockets for passenger transportation between cities
- a battery-powered hypersonic jet
- Mars colonies any time within the next decade
That stuff is so transparently daft and Sci-Fi-y, it makes my head burst with cognitive dissonance.
> That is surprising, and at odds with everything I've heard about the man in the last years.
Well, discourse online about him is utterly absurd. Sth that especially gets me is people who compulsively include "Emerald mine" thing.
Link to a fragment of Lex Fridman episode featuring John Carmack, who talks about Elon: https://www.youtube.com/watch?v=IQro0rkg2DE
Quote (I've broken it into chunks and slightly cleaned up, but there's ~no interpunction):
i think in many corners he does not get the respect that he should about being a wealthy person that could just retire and he went all in where he was really going to.
you know he could have gone bust and there's plenty of people you look at the you know the sad uh athletes or entertainers that had all the money in the world and blew it he could have been the business case example of that
but the things that he was doing space exploration electrification of transportation uh solar city type things these are big world level things and i have a great deal of admiration that he was willing to throw himself so completely into that
because in contrast with myself i was doing armadillo aerospace with this tightly bounded... it was john's crazy money at the time that had a finite limit on it. it was never going to impact me or my family if it completely failed and i was still hedging my bets working at id software at the time when he had been you know really all in there
i have a huge amount of respect for that and people do not
the other thing i get irritated with is people that say it's like oh elon's just just a business guy you know he just was gifted the money and he's just kind of uh investing in all of this
when he was really deeply involved in a lot of the decisions you know not all of them were perfect but i know he cared very much about engine material selection propellant selection and for years he'd be kind of telling me things like "get off that hydrogen peroxide stuff, liquid oxygen is the, it's the only proper oxidizer for this
like the times that i've gone through the factories with him we're we're talking very detailed things about how this weld is made how this sub assembly goes together, what are like startup shutdown behaviors of the different things
so he is really in there at a very detailed level and i think that he is the best modern example now of someone that tries to that can effectively micromanage some decisions on things on both tesla you know and spacex to some degree where he cares enough about it
i worry a lot that he is stretched too thin; you get boring company and neuralink and twitter and all the other possible things there where i know i've got i i've got limits on how much i can pay attention to
i have to kind of box off different amounts of time and i look back at my aerospace side of things it's like i did not go all in on that i did not commit myself at a level that it would have taken to be successful
Perhaps also you overestimate what being an engineer implies wrt skills and knowledge.
I'm pretty sure I saw the same list of sources praising Musk, and it was almost exclusively people that currently worked for him. I can't imagine any of Musk's employees being allowed to say "Oh sure, my billionaire boss is actually kind of useless as an engineer".
I think Musk is an exceptional CEO, who for some reason wants to be known, instead, as a genius inventor and engineer. He's a great businessman who wants to LARP as Tony Stark.
That doesn't work, because Tony Stark is LARPing as Elon Musk.
https://www.esquire.com/entertainment/movies/a40871355/tony-stark-iron-man-elon-musk/
Or maybe they're caught in an infinite feedback loop?
...and that's how the world ends.
We Software Engineering types love to smack talk Bill Gates, but back when all he did was sling code he was astonishingly good at it.
The people who only know his current persona never knew “Microsoft Bill” or numerous business flubs. Sure Bill himself lucked into IBM’s miscalculation as to the potential of personal computing, but if he couldn’t make his code work on an (iirc) 4k ROM, he’d just be another Harvard dropout.
> I think many engineers would quibble with the characterization of Elon Musk as an engineer, let alone a brilliant one
Everyone who has claimed this has never met Elon, while every engineer or scientist who has actually met him agrees he's an engineer. As an engineer myself, I know which sounds more plausible to me.
My direct evidence is his series of interviews with the everyday astronaut where he ends up giving an impromptu 30min technical presentation about the raptor engine.
I've met my share of pointy-haired-bosses and they didn't know that level of detail on their own product.
> I think many engineers would quibble with the characterization of Elon Musk as an engineer, let alone a brilliant one
I know John Carmack (who has a rather high credibility) doesn't. What explains this?
> …but am generally not impressed.
Same. AM’s Twitter is mostly a dumpster. He’s clearly trying to ride Ivermectin into the spotlight.
Yet I still find these posts valuable due diligence. Thanks.
"My usual heuristic is that when studies contradict, I trust bigger studies, more professionally done studies, and (as a tiebreaker) negative studies - so I leaned towards the studies finding no effect."
The debate really comes down to the validity of that heuristic. Trusting bigger, more professionally done studies would be a great heuristic if we assume corporate money does not corrupt scientific research. But this is of course a false assumption. I trust small studies done by doctors trying to treat patients in a third world country over large, professionally done studies brought to you by Pfizer.
I believe BigPharma is completely corrupt, and countless civil lawsuits and corporate criminal prosecutions bear this out. These corporations also corrupt the regulators, universities, and contractors who rely directly or indirectly on their patronage. In short, I rely on the Upton Sinclair heuristic - “It is difficult to get a man to understand something, when his salary depends on his not understanding it.”
Leaning towards negative studies would be a good heuristic in the case of patented and thus potentially lucrative drugs, but not in the case of generic drugs threatening a BigPharma income stream. Based on the foregoing, I don't have a strong belief that Ivermectin is effective as a Covid treatment, but I do lean in that direction based on the Upton Sinclair heuristic. You can go into all the studies and present critiques and counter-critiques until the cows come home, but it really just comes down to which heuristic you apply.
1. Big ivermectin studies have failed pretty consistently over long periods. You would need pharma companies to have meddled with studies from before their own drugs were ever approved, in the hopes that their drug would be approved later. And then after their drug had become standard of care, in order to prevent the previous meddling from being found out.
2. About 50% of Phase III trials fail. These are the big studies where pharma companies have already invested tens of millions of dollars into a drug, and now they have one big study to prove to the FDA that it really works. These studies are usually done by the pharma company itself, albeit with FDA oversight. If pharma companies can't even fix their own studies of their own drugs when tens of millions of dollars are on the line, why do you think they would so consistently bring out all the stops for a drug that *might* compete with their drugs later on?
3. Why did pharma companies let corticosteroids look good in studies and become standard of care for COVID?
4. I mentioned in Part 7 that using IVMMeta's methodology, basically every drug and supplement is a miraculous COVID cure (see https://substackcdn.com/image/fetch/w_1456,c_limit,f_webp,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F3e83bb87-2893-4c69-b71c-604782896641_717x671.png ). Do you believe Big Pharma is suppressing all of these, or just ivermectin?
5. Several of the big studies that failed weren't American - do you believe US pharma companies were able to rig these too?
1. I don't understand this claim. My understanding is a bunch of small trials showed promising results, then the Together trial was put forth as ending the question once and for all. Meanwhile, the Oxford trial ended under suspicious circumstances with no results forthcoming. I'm unaware of big early IVM trials repeatedly failing in the early days of Covid. And everything about the Together trial stinks. Putting forth an initial protocol of a single low dose of ivermectin cannot be reconciled with an intent to discover the truth in the best interests of patients. The initial Together ivermectin protocol was such obvious bad faith that one can't help but become extremely skeptical of the whole industry and everything that comes out of it.
2. BigPharma can only do so much. Obviously I'm not claiming there are zero checks. There are just inadequate checks and lots of ways around them. I would guess of the 50% of Phase III trials that succeed, most of those are actually garbage drugs, as most drugs are actually garbage drugs. I've been prescribed all kinds of garbage drugs (and now take none and am healthier than ever). Vioxx is of course exhibit A for garbage drugs getting through the system, and there's no reason to believe it was a real outlier. There's no reason to believe the Vioxx trials were conducted in a dramatically different way than other trials. In support of claim that most drugs are garbage, see, e.g., https://www.newscientist.com/article/2209477-why-most-new-medicines-are-no-better-than-existing-treatments/, https://studyfinds.org/big-pharma-fail-no-evidence-of-added-benefit-in-most-new-drugs-study-finds/. A high percentage of the "successful" trials are showing benefits that do not exist in the real world.
3. BigPharma can't tank every study. Sometimes real science happens, even in medicine.
4. I don't know why ivermectin became the target of BigPharma, the regulators, and the media to the extent it did, as opposed to other drugs and supplements. The whole campaign against ivermectin was bizarre, even if one accepts that it is an ineffective treatment. I'm not aware of similar campaigns against other treatments, and I have no explanation for the absence of such campaigns.
5. BigPharma is global. Yes, BigPharma can manipulate studies conducted in other countries.
Huh, I thought that the reasons for the media frenzy were obvious. The other side of the culture war happened to take ivermectin as their rallying banner, so the usual weapons were deployed.
Sure, but there were many other popular treatments. Indeed, the popular FLCCC protocol consisted of a cocktail of supplements and generic drugs, not just ivermectin. But ivermectin became the leading target.
I guess that the "horse dewormer" dig was just too good to pass up.
"The whole campaign against ivermectin was bizarre, even if one accepts that it is an ineffective treatment. I'm not aware of similar campaigns against other treatments, and I have no explanation for the absence of such campaigns."
Were any other medications touted as a miracle cure by as many people as ivermectin was, with as little biological plausibility to support it? If you got a big fire, you need the big hose to put it out.
It seems to me that there is an isolated demand for rigor that was applied to Ivermectin that was not applied to the Pfizer vaccine, even though Ivermectin has a much lower side effect profile. Call me cynical, but I suspect this has to do with profitability.
The side effect profile is secondary when there are fundamental doubts about the efficacy of the stuff. A medication can be as cheap and safe as it wants - if it doesn't work, and the promise of it working keeps people from taking a vaccine that has been shown to reduce mortality by an order of magnitude, that is a problem (especially at a time while the earlier variants were circulating, which were deadlier, but more effectively suppressed by the vaccine than Omicron).
The Pfizer trial showed more deaths in the experiment group than the ontrol group.
(And Pfizer has a long history of fraudulent medical research.)
And in many cases, the jabs were pushed on people without informed consent. But please do link the evidence that the jabs reduced mortality by an order of magnitude along with the longterm safety data.
The side effect profile is crucial here. There’s no question that ivermectin is safe. Accordingly, there was no fire that needed putting out, anymore than there needs to be a war on vitamin C supplements. The proposition that ivermectin caused “vaccine hesitancy” is unfounded. True, many of the same people who believed ivermectin was effective also believed the jabs were dangerous. But this is a correlative relationship, not causal. Both beliefs are secondary to distrust of the establishment.
"Putting forth an initial protocol of a single low dose of ivermectin cannot be reconciled with an intent to discover the truth in the best interests of patients."
For the conventional use of ivermectin, a study found that a single dose rather than multiple doses was the best method. This may be why that was the initial protocol used.
https://pubmed.ncbi.nlm.nih.gov/31558376/
"Interpretation: Multiple doses of ivermectin did not show higher efficacy and was tolerated less than a single dose. A single dose should therefore be preferred for the treatment of non-disseminated strongyloidiasis."
I suppose that could be put forth as a justification, but I don’t find it persuasive. Groups of doctors were putting forth specific ivermectin protocols, most notably the FLCCC protocol. The matter of public interest was whether those protocols were effective. All of those protocols called for much more than a single low dose. To deviate dramatically from those protocols and then offer your trial as debunking those protocols strikes me as bad faith.
With respect to Big Pharma, Big Studies, and the priors we should place on them, I think its imperative to consider the unitaid/Hill/Lawrie audio tapes.
Not only do we know of at least one high profile instance of monied interest putting their thumbs on the scale in a way that would make the most cartoonish-villain tobacco executive blush; what was perhaps more damning was the deafening silence around it. Not only can you do these things; we live in a world where you can do these things with zero consequences.
Its that silence in particular, that causes me to update strongly away from the Big Studies; which are the natural targets of monied interests, over the plethora of small independent studies.
Agree completely. Well said.
@Scott Are you planning on adding Biber to your mistakes page? Anything where you have to write "I was egregiously wrong, and I apologize to the study authors and to you." probably qualifies. I'm not writing this as any kind of attack; I just want to see that page remain up to date because I think it is one of the keystones of your credibility: I can trust you because you will tell me when you've been wrong (and not just in the depths of some post that I might not have read, though that's already an impressive and unfortunately rare step).
Thanks, I've added it in.
I feel like this is the best post that could have been written about a debate so full of sound and fury (and in many dimensions, not signifying nothing). At one point I felt like my eyes were bleeding from the point by point depths of discussion. At another I was blessed by the novel exposure to funnel plots and their interesting and likely significance. And at another by the graph that doesn't think it's about publication bias. At all points by the way this all works as a parable about how to debate and how well meaning people can perhaps go wrong and what it looks like to keep doing it
I was familiar with Alexandros' arguments before your original post and I respect his general capacity and attitude. I always doubted ivermectin but I was interested in the debate and nowhere else did I encounter actual debate. You two win by default, but also by a mile. It's quite understandable that someone with a high personal stake in something so high stakes made some personal remarks - but it would be worthy if he took them back
There are no personal remarks from my end. Scott has slung several insults towards me, and he is aware that I don't believe I have ever personally attacked him, even if he has done it. He still chose to leave that language in this article. Make of that what you will.
Nothing much to say about ivermectin at this point, though I still find it amazing how ivermectin was able to get 100s of times more interest and noise than fluvoxamine, which was probably the better hypothesis among the possible repurposing candidates, and was being researched around the same time period.
In any case, I find it weird that you would call your own mistake "offensive". I know these days being offended is kind of fashionable, but what on earth is offensive about a honest mistake in the middle of a best attempt at an objective take on a complicated and hot topic?
Yeah I wonder why Ivermectin is the one that took off and got popular, developed a legion of believers and scientist defenders. Was wondering if it's because it would be better known in rural areas . Fluvoxamine, on the other hand, is an OCD drug, sometimes also used for depression -- so maybe people in blue states are more likely to know about Luvox, people in red about Ivermectin?
I'd guess it's more that the "haha stupid vax deniers are taking horse medicine" angle that made it a lot more inflammatory and memetic.
My impression is the vax deniers started talking about IVM before the most of the Left became aware they were doing so.
One reason could be that people can buy ivermectin for veterinary use without a prescription, whereas there's no legal way to get fluvoxamine without seeing a doctor.
> would I bet even money that they'd see "statistically significant" 10% reduction in mortality? Thinking about it as hard as I can, If I felt I could trust the scientists to not pull any dirty tricks, I think I still would, yes.
I am impressed to see an answer that's not a panacea complex.
This is so different than what IVM fans were saying in 2021. Bret and Pierre were talking about using IVM to drive covid to extinction on Rogan that year. Pierre was going further saying it's likely to be a general purpose antiviral.
If people had said "take this in reasonable doses and maybe it shaves a few days off" the 2021 discussions would have went so much more smoothly.
Youre confusing the use of ivm as prophylactic against the earliest variants in a seronegative population with the use of ivermectin against omicron as early treatment in a mostly seropositive population.
That said, the extinction thesis was probably wrong when it was articulated, even just considering sars-cov-2 had spread to animals such as deer.
Not confusing them, comparing a reasonable take on its potential for treatment to the much much more unreasonable “not only is it a treatment, it’s a general use antiviral.”
Point being, if you had went on JRE in 2021 and said I think there’s a 50/50 chance of IVM lowering mortality in a very well-designed study, I would of had zero problem with that statement.
The avatars of ivermectinism were making much grander statements than that much earlier on.
Sure. Just keep in mind that essentially everyone recommending ivermectin was doing so as part of an extensive multi-drug protocol, so the various hyperbolic statements you've probably heard are ones selectively taken out of context, or ones corrected shortly after they were made, and were always contradicted by what was being recommended to people.
I mean, maybe. I never heard Bret or Pierre formally update their positions from JRE 1671: https://open.spotify.com/episode/7uVXKgE6eLJKMXkETwcw0D
That podcast was perhaps the exact moment where I went from being a Bret fan to being like"OH MY GOD BRET WHAT THE FUCK HAPPENED TO YOU!?" And that was when I stopped paying much attention to him and others in that camp. There might have been some value in continuing to track their intellectual progress, but there's only so many hours in a day and I wanted to find the best signal to noise ratios in the pandemic. I hope he updated and I hope he can let go of some of the pandemic takes.
I have no idea what specifically you are referring to, so I couldn't tell you.
"I wish other people would do this so I could stay in my lane of sniping at people with bad opinions about antidepressants."
I'm interested in reading this sniping about antidepressants. Any links to SSC/ACX posts on that topic?
You'll find a bunch at https://slatestarcodex.com/tag/psychiatry/
https://slatestarcodex.com/2015/04/18/polemical-imbalance/ is a hoot.
For all who could use a little comic relief at this point, here are 3 DALL-E images of the Ivermectin debate. The prompt was "two men having an intense debate about a medication for intestinal parasites."
steampunk: https://i.imgur.com/VlmdSZX.png
surrealist: https://i.imgur.com/iItysT1.png
And, Scott, especially for you:
stained glass: https://i.imgur.com/mKcsP8J.png
Might look elegant as a dining room window.
Good heavens - what a waste of time on balderdash and trying to play it through disagreements on statistics.
Where the hell were you when the Pfizer and Moderna info had to be forced by a judge to release it within 75 years ?
You can say what you believe and I will continue to believe what I/ we my spouse and 7 members of a Vet’s coffee group have experienced.
We have been on prophylaxis dose of IVM for nearly three years, surrounded by Covid victims in our daily lives, close contact with positive testing individuals.
A coffee group meeting every MWF every week for many years - 7 members have all gone thru their 3-4 x Covid infections and all have treated with IVM at proper 0.2 - 0.4 - 0.6 mg/kg doses as per flccc.net protocols excepting they took the 0.6 mg when having Covid to get over it but then stopped the regular dosage after getting well with a 5 - 7. day course of therapy, only to gain another Covid infection several months again later.
You can browbeat and try stats to kill off IVM but we will continue our usage for prophylaxis for as long as the idiocy continues.
You would be better served and maybe be accepted more readily if you chose to use the fraudulent results
Of Pfizer, Moderna et.al 60 day trials which more align your thoughts.
You keep your results and we will keep ours and obviously never the twain shall meet.
But we know our friends and fellow IVM users will be around to meet again and again as against the bullshit you keep trying to kill it off while ignoring the works of RCT’s with proper dosage and protocols.
"You can browbeat and try stats to kill off IVM but we will continue our usage for prophylaxis for as long as the idiocy continues." Jeez, miner, if you really think the stuff protects you I don't think you should only keep taking it as long as "idiots" like Scott keep making the case Ivermectin doesn't work. That would be a sign you are mostly taking it to defy Scott -- you know, like a teenage guy dying his hair pink to upset his mom. I really think you should keep taking Ivermectin as long as you believe your health is in danger.
You might take notice that I could take this post, replace ivermectin with some alternative medicine thing you don't believe in, and you would probably laugh at it.
I also haven't gotten COVID at all in the past three years, even though my wife and almost all my friends did. Sometimes you just get lucky.
I think you misread his comment as saying he never got COVID but he actually got it 3 or 4 times, he just didn't die from it (what I assume he means by 'covid victims')
Do you think that not having gotten it at all is more likely at this point than an undetected asymptomatic case?
Wow, a coffee group! Yeah, that beats everything else for rigour and repeatability!
Look, I'm glad you and your friends didn't get sick. Except for those of your friends who did get sick.
I and other family members also got sick. We didn't use ivermectin and we got better the old-fashioned way (by suffering through it for a week or ten days, then it cleared up). It hit us all differently, for a couple it was no worse than a cold, for others it had worse symptoms but different ways.
So seven of your group got recurrent infections and got better again within a week. Just like the ordinary way of getting better. This doesn't mean ivermectin cured them.
Keep taking the cattle drench, it won't do you much harm and at least you'll be free of worms!
I take paxlovid for worms. What's good for the goose.....
Hmmm - has anyone tried infecting people with worms to see if that shifts covid?
They did get sick "7 members have all gone thru their 3-4 x Covid infections"
Most people that catch COVID don't die, even the ones that never take Ivermectin.
Well I personally have been taking 8 fl oz of brown ale once a day in the evening after dinner as a prophylactic against COVID, and by golly it has worked, I haven't gotten the bug even once, even though everyone else in my household did. So ha ha to your nasty deworming pills, I've got a prophylaxis that works just as well but tastes great!
Ah, but do you have worms? There's the rub! 😁
Now that you mention it, no. My tipple must work against them, too. Awesome!
When did a judge make a ruling on releasing a Moderna document in 75 years?
I assert that this hasn't happened.
Reality > RCT's
I think the Sillicon Valley echo chamber got the best of you
Don't get me wrong I'm not saying IVM is a miracle drug but we keep asking for THE RCT study on IVM efficacy, knowing that it won't happen. No incentive to do it and a huge one not to.
Leaving patients untreated because there is no available RCT that determines its 'super effective and should be used worldwide'.
Look how long it took the USA hospitals to include sterocorticoids in their "treatment"
Did the medical community not know they help with inflammation??
I realize I'm derailing and you are actually focusing on the IVM published studies, but the bigger picture paints the context in which most of this
People died from bacterial pnemounia while we were too busy playing statistics
There have been four really big, extremely professional RCTs of the sort that would usually be considered Phase III trials (I think, not totally sure about the terminology) for ivermectin now. All of them found no effect. We're not waiting for THE RCT, it's already happened, multiple times. I agree if there had never been any big RCTs it would be reasonable to try it prophylactically.
Thank you for replying, you're right I phrased that wrong.
My point was more on the subject you already discussed with 'David' in the comments; regarding studies parameters and how we can manipulate variables to show the effect we are looking for...or no effect at all.
Admittedly I am pretty biased leaning pro IVM, really wish studies would/could show how it is an effective treatment option.
Here in Mexico we saw lots of patients quickly recover or had a pretty mild infection when treated early (tho IVM is not alone here). And we've seen the potential protective mechanisms of action in vitro. Correlation is not causation but there were just too many correlations not to take the signal seriously
Lots of patients with no medication recover quickly or have a pretty mild infection, especially now, because most people have had covid and many have also had a vaccination. Case fatality rate is way way down.
Given that ivermectin was so deeply plugged into the larger COVID conspiracy nexus, in which the pandemic was some combination of (Chinese bioweapon/not that dangerous/media invention/5G side effect/easily treated with horse medicine) done to (usher in world government/make money for pfizer/hurt Trump's campaign), I'm finding it incredibly hard to even care about the debate now that the pandemic is functionally over basically everywhere except China, which is already a semi-totalitarian state anyway.
Your initial post on this in Nov 2021 was a revelation. Thank you very much. This is far outside my field, and yours was an exhaustive review of the evidence to date on ivermectin (such as it were), as well as a summary of Dr. Bitterman’s fascinating hypothesis. I shared it with many colleagues. What a great read.
Well done here to respond to one of your strongest and most committed critics on this file. You’re not looking for pats-on-back but should get some anyway. Not every day you see mea culpa’s as you’ve done here. It’s a strong show of character.
On the science of ivermectin, however, it boils down to a simple first principle for me: the scientific method. The burden of proof rests with those who propose ivermectin to be of benefit. Until such time that they can provide causal proof of “benefit” via an RCT that reaches statistical (and also hopefully, clinical) significance, the only solution is to accept the null and reject their “hypothesis”. Anything else is just noise.
I’d also add that the requisite standard of proof needs to be met for any and all potential “use-cases” of ivermectin, such that there is no conflating btw prophylaxis and treatment; or of minor vs severe illness; early vs late; on O2 vs not; the list goes on. “Proving” a treatment “works” is a tough slog. It’s no wonder the ivermectin crowd shied away from it. Which is too bad, since globally they had the time to do many poor studies that were never going to be sufficient to prove causation, whereas that time should and could have been more gainfully spent on protocols that at least had a hope of answering the question. And of course, the later and typically western RCT studies showed no benefit.
As for the “wager”, that is silly talk best reserved for religion than for medicine (as you rightfully suggest). We don’t prescribe things that are useless just because they are safe. Your critic’s “wager” belies his religious fervour for ivermectin, in the absence of (appropriate) evidence.
It’s people like your good self that kept air in the conversation, many of us knew something wasn’t right and while it was obvious you would be attacked I commend you for standing your ground.
> But it got results p = 0.001, and you would need a thousand studies in file drawers to produce one like that. Weird.
I'm not sure if I'm teaching you to suck eggs here, but a p-value doesn't report the probability that the two groups in a trial have the same effect in real life, but rather the probability that the observed differences are due to chance. So a far more common reason to see a p-value like this conditional on ivermectin having no effect would be some subtle error of trial design like a loss of blinding or statistical error in the analysis.
It seems entirely plausible to me that an equivalent study that made a coinflip statistical error leading to p=0.999 wouldn't get published, so you only need to worry about the existence of one hypothetical unpublished trial, not thousands of them
I agree, but my claim was that I looked pretty hard for other errors, couldn't find them, and if I wanted to attribute it to publication bias alone it was a 1/1000 chance. I agree the most likely explanation is some completely hidden error that left no trace.
1. Thank you for the follow-up. Yes, in 2023 all work on ivermectin vs. covid looks pointless - but a lot generalises - and in Germany, Ivermectin was never a big thing in the public discourse to begin with (though at least Austrian pharmacies were sold-out, at times.)
2. I still feel your post was at least A- by content, not C. But sure, standards differ. This is the No1 substack on science - actually on rta - but still no habilitation. And no infamous NYT/WaPo.
3. The Carl Sagan/Pinker thing: Stuff must be true, but truth must not be boring. Your original post was not just very, very educative, it was hilarious. I was literally lol when reading and smiling for weeks after. Although on first clicking it, I doubted I would finish that post (that crazy worm-medicine? Dozens of studies reviewed? Meh. ) I would never have read this follow-up, if the original post had bored me.
> Gideon Meyerowitz-Katz
Completely off-topic, but I'm curious how a name like "Meyerowitz" comes about. -owitz is obviously the Slavic patronymic marker -ovich, rendered into German where the ch sound doesn't exist. Patronymics are based on the father's personal name.
So the suggestion appears to be that someone named Meyer had a son in a Slavic country who took an ordinary patronymic, that patronymic was somehow reinterpreted as a family name, and then at some point someone from the family moved to Germany. (Or, possibly more likely, someone of an unknown name started a dynasty in... say, Russia, they used normal Russian patronymics alongside their weird Jewish names the whole time they were there, and then eventually someone whose dad had been named Meyer moved to Germany, where everyone forgot about his family name and reassigned his patronymic to serve that purpose?)
Does anyone know which of those events likely happened in what order, and when/where the "Meyer" spelling is likely to have been introduced? I see on wikipedia that Meyer Lansky was originally named "Maier", which I assume can only have been pronounced exactly the same way as "Meyer".
Or am I interpreting "Meyerowitz-Katz" as a two-parent surname when in fact it's a completely normal patronymic accompanied by a completely normal surname, hyphenated for no particular reason?
AFAIK, the -witz in Jewish names usually means that their ancestors are from Poland.
OK, but it also means that at some point their family name, if any, was replaced by a name that is most certainly not their family name. That seems unlikely to have happened in Poland (but see below), where people would have understood what "Meyerowicz" meant. Did it happen to a big group of emigrating Jews all at once? Did it happen to a bunch of individual families over time? Did it in fact happen in Poland? I see there is a current Polish MP by the name of Jacek Włosowicz, while their MPs generally don't have obvious patronymics, which suggests the system may have fossilized inside Poland. Perhaps it did so over a relevant time frame?
What was the state of standardized spelling at the time? Would a Pole who naturalized in Germany today be assigned a respelling of his own name?
"Would a Pole who naturalized in Germany today be assigned a respelling of his own name?"
I can say with certainty that the answer to your question here is: Definitely not.
A lot of European Jewish names got mangled when the people moved to English-speaking countries, famously at Ellis Island but not only there. The person in question is Australian, so I can imagine the authorities in Sydney having a difficult time with Polish orthography and just trying to get it close enough based on what they thought they heard. Speculation of course.
Studies of the records indicate that names weren't changed at Ellis Island, where officials were matching with written documents, but later, usually by the families themselves.
https://journals.ala.org/index.php/dttp/article/view/6655/8939
Huh, TIL
This isn't exclusively true. My great great grandfather was Swedish and had been Carlson but took Svade (sometimes Swed) suggesting, perhaps, it just means "Swedish" when he arrived at Ellis.
I have family lore suggesting my mother's grandfather immigrated to the United States and commented that they'd gotten the spelling of his name wrong, which he was happy about. He would have had written documents (in fact, we still have documents of his).
The -ovich to -ovits sound shift is not plausible as a result of moving from Poland to Australia, since English already has a CH sound. (All Slavic languages including modern Polish use some kind of CH sound for this; it seems safe to rule out the idea that the Polish of the time had "ts" instead.) "-owitz" spelling has to come from Germany. (Or, I guess, some other German-speaking country?)
Why do you think that "son of Meyer" is a less likely surname than "Johnson"? If we're being picky, "Johnson" is a patronymic which has become a family name.
Looking it up, one explanation is:
https://dbs.anumuseum.org.il/skn/en/c6/e154774/Family_Name/MEYEROWITZ
"Meyerowitz is a double patronymic, in which both suffixes (the Russian "-ov" and the Polish and German "ow" and the German "-itz") mean "son of", making the literal translation of Meyerowitz: "son of the son of Meyer". Meyerowitz is based on the Yiddish Meyer/German Mayer (literally "farmer"). However, as a Jewish family name, Meyer is usually a form of the Hebrew male personal name Meir. In talmudic times, people credited with bringing light or intellectual clarity to their subject were given the name Meir (Hebrew for "illuminates or radiates" or "one who sheds light"). A 2nd century, disciple of Rabbi Akiva, believed to have been named Mesha or Nehorai (the Aramaic forms), was known as Rabbi Meir because of his keenness in shedding light on the Halacha (the Jewish code of law). Associated Jewish family names are Yair ("will illuminate") and the Aramaic Nehorai ("light") or their variants and patronymics. Similarly, the names Uri and Shraga (literally "fire"). Meir is documented as a Jewish family name in Arles, France, in the 13th century. It appears as Meiger and Meyger in the 14th century in Strassbourg, as Meyr in 15th century France, as Maier in Germany in the 18th century. Other variants include May in Germany and Poland, Major in Turkey, both in the 16th century, Mayer in France and Germany, and M'riro and Merito in Morocco. Named for their forefathers, families were called Meyerson, Meyerovitch, Meyrowitz, Merovic and Ben-Meir, all meaning "son of Meir".
Another short version has it:
"Meyerowitz Name Meaning
Jewish (Ashkenazic): patronymic from Meyer. The ending -owitz is a Germanized form of the East Slavic patronymic ending -ovich Polish -owicz."
So family name Meir/Maier gets further altered in Germany and/or Poland as "Meyerowitz".
So... Meir means “Lucifer” in Hebrew, basically? Is this guy Gideon the nephew of the Devil?
There has obvoiusly been a lot of linguistic confusion in the shared realms of polish, german and yiddish speakers. Transcription/Pronounciation rules differ (Szulc=Schulz for example) and the hebrew consonantal writing may have also contributed.
Very minor point, this sentence: "Ivermectin was originally an anti-parasitic-worm medication before being repurposed to fight COVID, and everyone agrees it is very good at this," is a bit confusingly written, because it's not clear what 'this' refers to. Later parts of the text clarify, but maybe you want to tweak the sentence in case someone decides to quote you out of context again.
Thanks for writing this up! I've actually mildly adjusted the other way after reading this, to be perfectly honest (and rather unexpected going in), but I think it's a good sign for rigorous reporting.
"Doesn’t this mean that the medical establishment wants to blame Cadegiani both for giving drugs that don’t work, and for not giving them to enough people?"
There are several pieces of context missing in this interpretation; here is a public note by the Brazilian Research Ethics Comitee https://conselho.saude.gov.br/ultimas-noticias-cns/2095-nota-publica-cns-elucida-a-sociedade-brasileira-fatos-sobre-estudo-irregular-com-proxalutamida (in Portuguese, but Google translate works well)
The main points were that he had ethics approval for a small study, on mild/moderate patients, in a single hospital in the Brazilian capital, and somehow the study ended up being conducted in several hospitals, in critical patients, in the Brazilian Amazon. Also, the consent forms handled to patients were not the same as the ones initially approved, and didn't contain many passages about patients rights.
This study had a 50% mortality rate in the control group, with a significant amount of hepatic and renal failure. The author says they were in the placebo group, but that wouldn't have been known as the deaths were happening, as it was a blind study and there was no effort on the part of the author to request unblinding to check if maybe the renal and hepatic toxicity was because of the maybe renal and hepatotoxic drugs. When requested, the author did not provide any data to provide the traceability of the medication, so it can't be ruled out that the placebo group was actually receiving medication. The "Independent data monitoring comitee" in the study was under the supervision of someone on the payroll of the pharmaceutical company making proxalutamide
So, either the study was properly blinded and he decided to not report excess Kinsley and failure deaths which could presumably be linked to the new, barely-tested drug, which would be a crime, or he knew that the placebo group had an overwhelming amount of excess deaths and didn't try to prematurely end the study, causing willful harm to the patients, which also would be a crime
I haven't been able to find any news on the subject since the police raid on the author's house last August, but this is unsurprising given the slow pace of the Brazilian justice system
> … or he knew that the placebo group had an overwhelming amount of excess deaths and didn't try to prematurely end the study, causing willful harm to the patients, which also would be a crime
I must be misunderstanding this sentence. How could ending the study have prevented harm to the placebo group, who were not receiving any drugs as part of the study? If the placebo group had lots of deaths, surely that can’t be because of the study, which only gave them a placebo … so stopping the study can’t help them … and continuing the study can’t harm them.
If I understand correctly
The author only observed excess death, and is blinded to whether the patient got placebo or not. So it is unethical to continue considering the excess death could be from real medication.
Considering the amount of excess death [50% (of what?) which is way higher than base line] and the possibly dodgy tracking mechanism. It is possible that the real medication might have cause the excess deaths and those deaths were later shunted into the placebo group causing the abnormal reporting.
Or he may have found the golden cure and refused to stop the trial leading to excess deaths.
50% of the patients in the control group, which consistent of hospitalized patients, not on mechanical ventilation, with a median age of 50 years, and 70% of which had no comorbidities, were dead after 28 days
This is a high amount even on patients receiving intensive care, which tend to also be older and sicker
Oh, I get it. If the study was improperly blinded, so that he knew who was in the placebo group, and he saw that they were having massively excess death, he should have given them the drugs the other group was getting, which would have seemed to him really effective and life-saving. Doing that would have ended the study, by definition.
When there's solid evidence of benefit, it is considered unethical to keep randomizing patients to receive placebo.
" The whole “repurpose existing drugs against COVID” idea seems to have been a big wash. "
I would paraphrase as:
"Because !IVM, and perhaps !FLV , then the space of all existing drugs & compounds prior to the advent of COVID at any dosage regimen are very unlikely to show any safe efficacy against COVID morbidity or mortality."
Would you mind characterizing the statement further?
I don't want to speak for Scott, but that is not a good paraphrase. You're claiming that Scott implicitly says, "among the many thousands of drugs that were not known to be useful against respiratory viral infections, there is probably none that is effective against COVID" - when the more realistic implied statement is "when you select and try a few out of the many thousands of virus-unrelated drugs, without a solid biological mechanism to guide the selection, you are unlikely to find one that works"´, and the literal statement is "the couple of (virus-unrelated) drugs that were selected and tested for COVID turned out to be duds."
So in my read both of the latter two statements are cheems as set against SA's swole dog statement.
We're also somehow seeing the exact same statement and interpreting it in two very different ways. Is the 'a big wash' vernacular implying that the search for repurposed drugs for the pandemic wasn't worth undertaking in the first place? Or does it just mean that the results of the repurposed drug search enterprise, in the way that we collectively went about it looking back, did not yield useful results (itself a debatable statement IMO, but that's beside the question at hand).
I normally interpret something being called "a wash" as meaning that it turned out to have no effect. I can't recall any occasion where I believe it was intended to mean "you should have known this would have no effect before you tried it."
But even if you interpreted "wash" that way, that seems to map squarely to FluffyBuffalo's suggested reading of "when you select and try a few out of the many thousands of virus-unrelated drugs, without a solid biological mechanism to guide the selection, you are unlikely to find one that works".
Do you believe Scott's statement suggests that in the event of a future pandemic, he would recommend against a repurposed drugs search undertaking?
I don't think a plain reading of this statement says that.
If I combine it with other things Scott said in this essay to form a gestalt impression and make a prediction based on that, then I predict that Scott would say that a future search is unlikely to succeed unless it has a stronger basis for selecting which drugs to investigate than this search had. But I'm not super confident in that prediction and I don't think Scott is making any specific effort to build that case.
Also, if your question is meant to somehow imply or build towards some argument supporting your original interpretation, then I don't understand where you're going with it. Even if I answered an unequivocal "yes", that would still seem more in line with FluffyBuffalo's suggested reading than yours.
As always, I appreciate Scott giving a hearing to folks with different perspectives, and I especially appreciate his integrity in transparently engaging with his mistakes and with points won by the other side. That said, it is hard for me to see the potential value in this discourse, for two main reasons:
1. I don't think that litigating and dissecting the reported details of 1-2 dozen small positive studies has scientific value. If there's anything we can learn from The Control Group is Out Of Control (https://slatestarcodex.com/2014/04/28/the-control-group-is-out-of-control/), it's that the epistemic value of scientific studies is much more limited, conditional, and contextual than we would like. Deep dives into the reported protocol don't necessarily help. Shoveling a bunch of small studies into a meta-analysis doesn't necessarily help, if their internal issues combined with the file-drawer effect are sufficiently severe. Genuine epistemic progress simply requires better studies with larger samples, more reliable protocols, etc. I am not aware of any instance in which applying overwhelming brainpower to small studies has produced scientific progress. It seems to me that, by the time we get around to the Conclusions on this post, Scott has basically come back to his 2014 SSC post. We know this style of science doesn't work because it can be leveraged to prove anything, no matter how nonsensical.
2. I place low trust in Alexandros as an epistemic agent based on heuristics I consider reliable. Alexandros' posts are saturated with emotional, dramatic, adversarial language, and he spends a visibly disproportionate amount of time litigating points of very marginal relevance. I have seen this pattern frequently online, and it is a strong signal of low-quality thinking. The fatal temptation of polemicists is to become obsessed with winning at the expense of truth. In their sprawling, point-by-point refutations of their opponents, it quickly becomes impossible for a third party to discern what the original point of the discussion was, or how the points currently being discussed tie back to it. It's hard for me to say what I learned from this post, except that even Scott, with his extraordinary thinking and writing powers, cannot turn a discussion of this type into something illuminating. I'm glad Scott emerged from the morass with some lessons, but it's hard for me to say the same.
I think it is time to invoke Shaw's adage about wrestling in the mud with certain hooved animals and move on.
The Biber et al. study looks interesting and is the one most likely to shift my opinion towards "maybe ivermectin does have a specifically anti-covid/anti-viral effect as distinct from killing off parasites which enables immune system to do better fighting the virus", but it's still "early treatment of non-hospitalized patients with mild COVID-19", so that tells us nothing about "can it work for severe cases?"
But I am solid on Flavio A. Cadegiani, M.D., Ph.D., M.Sc. and his alleged gold medals don't impress me much:
"His superlative achievements include amongst the fastest PhD obtained in the history of Federal University of São Paulo (7 months) and concurrent gold medals in Mathematics, Chemistry and Physics Brazilian Olympics in his adolescence."
I remain to be convinced about getting a PhD in seven months, and there seem to be a lot of different Brazilian Olympiads so without knowing which ones he entered, it's impossible to say if he did win what he claims, or if the particular competition was ranked highly.
As to his covid treatments, he didn't simply stick to ivermectin - he was pushing for an anti-androgen as another miracle cure, except unhappily that study got pulled for bad methodology (and he seems to have gone for the anti-androgen *after* the ivermectin work, so not reliant on ivermectin as being the sole single cure):
https://retractionwatch.com/2022/06/10/researcher-attacks-journal-for-retracting-his-paper-on-covid-19-drug/
https://www.science.org/content/article/too-good-be-true-doubts-swirl-around-trial-saw-77-reduction-covid-19-mortality
https://www.bmj.com/content/375/bmj.n2819
"Violations of medical ethics and human rights committed in a trial of an experimental drug touted by President Jair Bolsonaro as a cure for covid-19 were the worst in Brazil’s history, the country’s research regulator has said.
The clinical trial of proxalutamide “disrespected almost the entire protocol” and may have contributed to the deaths of as many as 200 people, said the National Health Council (CNS), which oversees clinical research in Brazil. Some of those people were not adequately informed of the risks they were undertaking in the trial, and some did not know that they were taking part in one, it said.
Brazil’s attorney general is investigating the possible violations of medical ethics and human rights on the recommendation of the National Research Ethics Commission (CONEP), which forms part of the CNS. The trial’s principal investigator, Flavio Cadegiani, was identified in October along with 68 others by a parliamentary inquiry into Brazil’s management of the pandemic as having committed “crimes against humanity.”
Proxalutamide is an anti-androgen that blocks the function of some male hormones. It is being tested by China’s Kintor Pharmaceuticals for prostate cancer, breast cancer, and other uses. It has not been approved for use in any country but was talked up by Bolsonaro as a treatment for covid-19. Shortly after recovering from covid-19 he asked why it had not been approved for use and promised to make it available to all of Brazil."
There's also the "conflict of interest" disclosure about Dr. Cadegiani, et al. on the ivermectin study:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525042/
"Lucy Kerris is a paid consultant for both Vitamedic, an ivermectin manufacturer, and is co-founder, as well as acting as a paid consultant, for Médicos Pela Vida (MPV), an organization that promotes ivermectin as a treatment for COVID-19 and discourages COVID-19 vaccination. Flavio A. Cadegiani was a paid consultant (USD 1,600.00) for Vitamedic, an ivermectin manufacturer. Dr. Cadegiani is a founding member of the Front Line COVID-19 Critical Care Alliance (FLCCC), an organization that promotes ivermectin as a treatment for COVID-19. Pierre Kory is the President and Chief Medical Officer of the Front Line COVID-19 Critical Care Alliance (FLCCC), an organization that promotes ivermectin as a treatment for COVID-19 and discourages COVID-19 vaccination. Dr. Kory reports receiving payments from FLCCC. In February of 2022, Dr. Kory opened a private telehealth fee-based service to evaluate and treat patients with acute COVID, long-haul COVID, and post-vaccination syndromes. Dr. Kory expresses personal points of view against COVID-19 vaccination. Jennifer A. Hibberd is a co-founder of the Canadian Covid Care Alliance and World Council for Health, both of which discourage vaccination and encourage ivermectin as a treatment for COVID-19. Juan J. Chamie-Quintero is a contributor to the Front Line COVID-19 Critical Care Alliance (FLCCC), lists the FLCCC as his employer on his LinkedIn page, and expresses personal points of view against COVID-19 vaccination."
He may well be an expert in sports medicine (though it would seem easier to be an expert in a field where you're writing the majority of the works) but I don't think he is trustworthy re: "don't get vaccinated, take my miracle cure instead":
"Dr. Cadegiani is the only author of the sole book in Overtraining Syndrome, the prevailing sport-related disease among amateur and professional athletes. He is also responsible for approximately 70% of the articles published in the field in the world in the last 05 years, and reviewer for more than 90% of the manuscripts in the field."
FYI, most of the doctors advocating for ivermectin were recommending multi-drug protocols such as the one by FLCCC or McCullough. I have yet to see one recommending only ivermectin and nothing else if you get COVID.
Throw everything including the kitchen sink in and see what works?
I'm just letting you know of factual evidence that the whole "miracle cure" story was wildly overplayed. Obviously the people putting together those protocols wouldn't describe them as you did, but that's a separate matter.
Since I think the FLCCC are a dodgy bunch, that's about as convincing to me as "Joe down the pub recommended this".
>This is a good place to note that I very poor memory of what I was thinking two years ago
Unless that's a joke I don't get you're missing a "have".
i am buying ivermectin from india and recived today.
I am shipping sugar pills as ivermectin from India. This should have no impact on your protected-ness from Covid. On the other hand, if you have worms, please phone us immediately.
You may as well, since the Indian government dropped their recommendations for ivermectin and hydroxychloroquine in 2021 as they didn't do a damn thing. They probably have a stockpile of drugs they might as well sell to gullible Westerners and get some return on their money.
https://www.indiatoday.in/coronavirus-outbreak/story/why-hcq-ivermectin-dropped-india-covid-treatment-protocol-1857306-2021-09-25
"The Indian Council of Medical Research (ICMR) and the National Task Force on Covid-19 have dropped the use of Ivermectin and Hydroxychloroquine (HCQ) drugs from their revised guidelines for the treatment of the infection.
The decision was taken after experts found that these drugs have little to no effect on Covid-related mortality or clinical recovery of the patient.
“HCQ may be considered for removal from guideline, with recommendation to use with caution only in clinical trial setting (since there is some genuine uncertainty regarding the possible benefit for severe cases and in low dose),” said the document titled ‘considerations for exclusion of Ivermectin and Hydroxychloroquine from the clinical guidance for management of adult Covid-19 patients’.
Several clinical studies have shown the low mortality benefit for HCQ, said the document. In fact, when HCQ is administered with azithromycin, it increases the risk of adverse drug effect (ADE) in patients, experts said."
Potential mistake:
"many drugs change secondary endpoints but fail to change the things we care."
Should there be an "about" at the end?
"In response to this section, Alexandros stresses that he is not necessarily saying Borody et al is incorrect or challenging my decision to leave it out." -> probably meant to be: [..]Borody et al is correct[..]
"[..] authorize it, it (according to Carvallo) it is [..]" -> one less "it"
> Alexandros has grappled with this same mystery, and taken a different route, Alexandros has wrestled with these same problems, but solved it differently.
I think this is a typo?
Scott, I do not need to tell you that you are an extremely talented writer. Why do you waste your precious skill and time answering to somebody without the credentials?
The TOGETHER trial, published in NEJM 2022 was negative. Done. This is the one observation that refutes the hypothesis that Ivermectin decreases hospitalization rate in patients with Covid-19. And it was done in Brazil, one of the countries with the highest prevalence of Strongyloides.
Much appreciated. I have a good impression of Alexandros's efforts in much of this and feel your post added further insight and nuance, regardless of one's prior.
A side of this I'd like your take on:
For me it seems not at all clear that Ivermectin would have an effect today. For one thing, Pierre Kory and many associated with him shouted a preliminary alert when delta was appearing, that it seemed ivermectin might not be nearly as effective on that variant and that all prior indications of likely ivermectin effectiveness should not be trusted absent new data from Delta and onwards.
1) Off the top of your head, does it seem probably to you that ivermectin was initially effective and a missed opportunity on the original strain but lost most/all of its advantage after variants?
2) Whether ivermectin is effective or not, seems very murky to me and ultimately of much less interest than whether our institutions acted appropriately by the data available. Much clearer than whether ivermectin is effective, I have a strong sense that there was a significant signal with low cost and risk that institutions were failing to explore and in many cases discrediting in deceitful ways. Do you have any thoughts on how appropriately any early indications were acted upon?
"The whole “repurpose existing drugs against COVID” idea seems to have been a big wash."
Dexamethasone is cheap and repurposed and is still one of the primary treatments for hospitalized covid patients requiring high-flow oxygen. This was confirmed with an early RCT from the RECOVERY trial.
https://en.wikipedia.org/wiki/COVID-19_drug_repurposing_research#Dexamethasone
https://www.covid19treatmentguidelines.nih.gov/management/clinical-management-of-adults/hospitalized-adults--therapeutic-management/
is there an "undeniable unbreachable fortress of evidence" for the Pfizer vaccines?
Why is that the standard for IVermectin but not for the newfangled, non-immunizing treatments that causes heart attacks but are still mandatory. (i.e. Pfizer/Moderna vaccines)?
Indeed, those are good questions. What is the standard of evidence for mask effectiveness or Tamiflu?
What are the odds that the recent MedinCell PR is true vs. bogus? I'd say 50/50. https://www.clinicaltrialsarena.com/news/medincell-covid-19-prevention-trial/
The result is claimed to be strongly positive for early treatment. Does it contradict any "high quality" trials? I think ACTIV6 and TOGETHER were later interventions. The devil is in the details, and Alexandros' takedown of ACTIV6 was convincing, especially as regards the study authors' mixing up of Bayesian confidence (ideally 1) and p-values (ideally 0). https://doyourownresearch.substack.com/p/activ-6-trial-ivermectin-scientists
FWIW, I also respectfully asked the corresponding author about a seeming inconsistency in the paper (by email from a top .edu address). No answer.
>I will repeat that my strong objection, is that you wrote " this is not how you control group, @#!% you". I therefore pointed to stat news to support my case that, yes, this can indeed be how you control group. That's all. In the article I even noted that this aversion towards disrespect to elders may even be a cultural difference between us. To be clear, if I were making a case for ivermectin, I would not be relying on this study as my starting point.
Okay, but I have to ask, what *is* Alexandros making the case for? Is he trying to make a case for ivermectin, or simply saying that you're being insufficiently respectful to the people who study it? Because "This methodology exists and is used in a couple of specific cases that have nothing to do with ivermectin" is irrelevant for the first, but a 21-part essay titled "The Potemkin Argument" seems a little overboard if all he wants to say is that Scott is sometimes snarkier than he should be.
In general, Alexandros's responses give me the impression of "JAQ-ing off" - switching back and forth between "Here's the case for Ivermectin" and "I'm not making an argument for ivermectin, just pointing out some methodological issues on the anti-ivermectin side" depending on how well each individual part of the argument holds up. But if you start off by comparing your opponents to Russian propaganda, then I'm going to be a bit dubious that you're approaching this in a spirit of collegial truth-seeking.
The case I am making, which you will see in the piece Scott is responding to, is that Scott's original piece is riddled with factual and logical errors, (which I document with specifics) and in addition, maligns honest scientists, while not displaying a fraction of the rigor he demands of them. What's more, my most deep disappointment has been with the rationalist community, that not only has not pushed back on a piece this influential and this wrong coming from one on their own, but if anything seems to endorse it.
This is impressively detail oriented. It also maybe loses sight of the framing of this whole discussion.
Marinos' arguments are merely the motte to Weinstein's bailey.
Marinos argues that we should simply take a chance on ivermectin treatment, because it's harmless and it seems like it maybe works, if you squint at the data just right and disregard all the largest trials as corrupt.
Weinstein argued that we could stop the pandemic by using ivermectin, that the suppression of ivermectin proves that the institutions are captured by big pharma. Along with many others, he argued that you shouldn't get vaccinated because vaccines are unsafe and ivermectin is at least as effective.
Marinos, sites like ivmmeta, and no shortage of other Substack writers offer just enough rigor for that argument to be plausible.
I originally took an interest in ivermectin because some of my friends and family bought that argument. They did not get vaccinated, they caught covid, they bought hydroxychloroquine and ivermectin from some telehealth providers. None of them died. But they got plenty sick and didn't recover quickly. It sure didn't seem like a miracle cure.
In that case, we've moved on from Omura's wager -- "if it's even 10% effective, ivermectin could save so many lives". We've moved to, "is it as effective as the covid vaccines?"
As of 2021, the FLCCC recommended ivermectin as the primary treatment for covid and briefly suggested you talk to your doctor about maybe getting vaccinated, almost as an after thought. As of today, I believe they recommend not to get vaccinated at all. In fact, Dr Kory now recommends against vaccinating children for any diseases, not just covid:
https://twitter.com/PierreKory/status/1606830454006587393?cxt=HHwWgoC9lZvyzcwsAAAA
And, of course, Omura's wager was always a forced binary, so the motte itself is hard to defend.
Scott explained this well in "Pascallian Medicine" -- you could make the same argument for taking any and every reasonably safe drug when you get covid. Maybe one of them helps? Who's to say otherwise? Why not take 20 drugs?
Had I gotten covid in 2020, I would have gone ahead and taken vitamins, zinc, aspirin, low risk things like that, despite having low certainty that they would help. But I never understood why ivermectin moved to the top of the list of things to experimentally take. What made it any better than other speculative treatments, like fluvoxamine or metformin or bromhexine or camostat? Just the popularity on Youtube?
If ivmmeta's methodology for evaluating drugs is correct, why do we even need ivermectin? They think quercetin works just as well and melatonin is close.
Where were all the podcasts telling people to take quercetin and melatonin? Wouldn't those save more lives?
I suppose the government can't suppress those drugs, so you can't make a conspiracy theory out of any of them. And you'll get a lot less Substack subscriptions that way.
Re: "The whole “repurpose existing drugs against COVID” idea seems to have been a big wash."
COVID-OUT seemed to report good results for metformin, with both a 40% reduction in ER visits and long covid rates:
https://www.nejm.org/doi/full/10.1056/NEJMoa2201662
https://www.medrxiv.org/content/10.1101/2022.12.21.22283753v1
Remdesivir was a repurposed drug that proved to be highly effective (but expensive and impractical, since it only worked well if injected early enough)
I still wonder if the related drug GS-441524 could have also worked as an oral version. I'm not sure, maybe you can't hit a high enough concentration that way.
And I wonder if there are drugs we missed entirely, by not testing them in large enough trials.
I think there are still a lot of good questions.
One is why "early treatment" supporters haven't pivoted to metformin:
https://medium.com/microbial-instincts/ivermectin-failed-in-a-high-dose-trial-but-metformin-might-help-treat-covid-4599720b0c22
I think the answer is easy: Most of them are selling blogs and videos, so they need to talk about popular topics. Vaccine and ivermectin conspiracies will remain the product for as long as it's the most lucrative thing to talk about.
It also raises more important questions, like: what's the bar for getting the FDA to actually care about a generic drug? Would a second trial confirming COVID-OUT's metformin results be enough? Can that be done in under a year? Is it possible to still get statistical significance now that the virus isn't killing as many people?
In general, it seems like we need a breadth first search for treatments that isn't biased to approve a patented product over a generic. And we need that search to work a whole lot faster, if it's going to save any lives in the next pandemic.
Right now we have one process that works pretty well for patented drugs. And we have some sort of chaotic process that throws lots of attention towards whatever's popular on Youtube. Is there some third approach which could find cheap treatments faster?
Quick question. All I wish to know about ivermectin- is the risk/reward ratio worth taking? You appear to be conceding a sizable amount of your early analysis to rather embarrassing (your words. I'd call it credibility suicide, but I'll go with your description) yet somehow claiming a stronger argument on your own behalf as a result..
This reads more like a last ditch ego stroke to satisfy your own fanboys than a refutation of his work. He has put in the effort and done the math. I would not judge him to be pro ivermectin, simply because he proved you wrong.
At the core of this debate, there seems to be no disagreement. You were mistaken on multiple points. There is no value in your concession or apology if the end result is merely to assuage your own guilt for failure to analyze the situation beyond the popular media tropes. .
You have defended the popular belief, poorly, and when eviscerated for your inability to reach a conclusion which matches the facts, you've responded with even less facts, yet still declared victory.
I have heard of you as an example of the rationalist community, but I think you may have left some letters off the self assessed title. Clearly this is rationalization and nothing more. Title yourselves appropriately, please.
Also a couple direct criticisms-
"In contrast, the pro-ivermectin side did an amazing PR job. "
You mean the side that didn't have a billion dollar advertising subsidy to promote itself and was maligned by every institution, agency, and media conglomerate with access to a broadcasting. antenna won the pr war on this one? On one side you have billions of dollars of efforts and an infrastructure built on concepts of Total Information Control and Awareness and the other side have Joe Rogan and Joe did an amazing job? That seems rational and reasonable.
"I give myself a C+ for results but an A for effort. I wish other people would do this so I could stay in my lane of sniping at people with bad opinions about antidepressants."
If everyone gets a trophy? Sure. You got it big guy. Take 5 gold stars for your work, as well, On the other hand, for actual value to the species in this situation, let's await a more objective judgement if you don't mind. Going out on a limb, I'd guess this is your swan song and very last bit off influence on the public discourse, but I have been wrong before and certainly will be again.
This is not a useful comment. Do you have anything of substance to say beneath all the insults? Scrub them off and try again.
Agreed. For anyone who has followed Alexandros, this is a deeply disingenuous and unsatisfying response, but it is par for Scott's MO when he throws out his whole rationalist dogma to just go with his gut:
1. Decent steelman review of the opposing side
2. Humorous and sincere response
3. Very detailed review of some individual point with apparent concessions
4. Brief hand waving dismissal of the strongest and most relevant points (in this case the large industry funded studies that used *different protocols* from the studies on IP-protected drugs)
5. Quick, poorly-defended Hail Mary (i.e. parasites, new studies)
6. Non-sequitur conclusion and declaration of victory.
This has been an especially interesting debate because Scott is rhetorically much more effective while Alexandros has been more dutifully rationalist.
Ah, the fanboys are showing up again. And still irritating this time round.
"...but I have been wrong before and certainly will be again."
But *that* quickly? Impressive!
Does this change your original conclusion of "85%-90% confidence" that ivermectin doesn't work?
First off, I can't say how deeply I appreciate you correcting on the meta-analysis function (which I believe I railed at you about, sorry), if everyone had the guts to correct their math post-factum the world would be a better place.
Personally I still see the problem here being that medicine, using current trial approaches and statistical methodology, can't prove or disprove any intervention really works for anything, it got stuck at penicilin and smallpox vaccines, everything beyond that is a bunch of interesting drugs (some of which you can try, and might work) that have no real clear effect.
You can't study single digit effects on covid because it's either very fuzzy (time to negative PCR-T, symptom reduction style endpoint) or very niche (mortality from a disease that doesn't kill that many people, and almost always kills in conjunction with a host of other morbidities). Nor is this a good thing to study, we should either aim for drugs that work so well the endpoint, drugs should cure things, and we had drugs that cured things. But when they stopped working we redefined the endpoints instead of redefining drugs.
The proof for this is to look at any life expectancy numbers, the US added 8 years since the 1960 (10 if you discount covid), compared to 22 in the 60 years before that point -- in spite of <points at all the problems in the first half of the 20th century> -- We got vaccines for smallpox, hep a & b and polio, we figured out antibitoics --- then the well ran dry, and we've been grasping at straws that one can adjust away with better food or removal of pollutants or sewage.
This kind of debate is the thing that happens when you've given up on hopes of curing disease and moved the marker to 2nd or 3rd degree aggregated statistics.
I have followed this since the start. In many respects, "can't see the wood for the trees" comes to mind. I am pro ivermectin but it is not available to me here in the UK so For prophylaxis I take Multivitamins, C, D3, zinc AND Quercetin as the ionophore. (Mercola Qurcetin articles and other studies show benefit).Got cold like symptoms once in 3 years. Never masked, never tested with PCR so I do not know if I had Covid. However, I now have parosmia so smell and taste ruined. Onion, garlic and certain toiletries are disgusting to me now. Meanwhile, not a hysterical Alex Jones type analysis....
https://21stcenturywire.com/2023/02/01/covid-19-vaccine-a-military-response-to-a-public-health-threat/ covers the framework and mechanism building on Katherine Watt and Sasha Latypova work around the bioweapon. Long but thorough. Far more pressing than a spat about a suppressed Nobel prize winning, cheap, safe and effective molecule that has been around for decades. Remember, EUAs predicated on no treatments available. Dont get me started on HCQ and the murderous Oxford overdosing trial. Dont worry after all is over we can Build Back Better. I mean us, not Schwab, Tedros, Gates, Fink and their cronies.
Lurker here who carries out systematic review and meta-analyses in academia on a daily basis. Publication bias and funnel plots are better described as the study of "small study biases" than "publication bias" (but the original name has stayed and it would be hard to change it right now...).
Publication bias is one of many explanations, but typically the wrong one. The most likely explanation for assymetry is not that studies carried out suddenly dissapear. Instead, this assimmetry is more easily explained more typically related to p-hacking or other QRPs (Questionable research practices), or more generally poor experimental designs.
It is far easier to shift an effect through p-hacking /QRPs/poor experimental designs in a noisy small study and shift a negative result to more positive one, than in a less noisy and bigger one. Hence, the assimetry does not come from not publishing studies, but from tweaking small negative ones into positive and then publishing them.
This is so in general, but even more likely in this case (where it was aligned with conflicts of interest and political motivations). In this regard, the fourth argument (which is the only one specific to these set of studies, and not against funnel plots in general) is basically baseless.
How about shifting a positive result to a negative one? Is that hard to do in a big trial? For instance with techniques like these? https://doyourownresearch.substack.com/p/10-questions-for-the-together-trial?s=w
This entire discourse has driven me to find refuge in poetry. Take it away, Alexander Pope:
A little learning is a dangerous thing;
Drink deep, or taste not the Pierian spring:
There shallow draughts intoxicate the brain,
And drinking largely sobers us again.
Fired at first sight with what the Muse imparts,
In fearless youth we tempt the heights of Arts;
While from the bounded level of our mind
Short views we take, nor see the lengths behind,
But, more advanced, behold with strange surprise
New distant scenes of endless science rise!
So pleased at first the towering Alps we try,
Mount o’er the vales, and seem to tread the sky;
The eternal snows appear already past,
And the first clouds and mountains seem the last;
But those attained, we tremble to survey
The growing labours of the lengthened way;
The increasing prospect tires our wandering eyes,
Hills peep o’er hills, and Alps on Alps arise!
Does anybody else find it funny that there was a whole debate over the statistical validity of funnel plots while letting p-values slide?
They go all-together... As I disscussed above, fudging with p-values is a likely explanation for an assymetrical funnel plot.
In any case, both are tools that can be (frequently are) misused...
I wrote specifically that I am adopting the frequentist paradigm for the purposes of this debate, since that's what Scott is using, and I can make my point just as well. Of course the over-reliance on p-values is silly, but that's not the core of the issue with Scott's piece.
> gestalt vibes of untrustworthiness
Cue 37-part series from Alexandros explaining why Scott is Betraying Rationalism by including such a phrase.
I jest, but Alexandros has gotten *so much mileage* out of waging the culture war on this topic. He has worked very hard to frame his stance as simultaneously subversive and indignant. This shouldn't detract from the legitimate research he has collected. But it does predict his response to any high-profile conversation with Scott.
Anything Scott says can and will be used...not exactly against him, but *for* retweets and Substack follows. That does mean against him if and when Alexandros can frame it as punching up.
So I'll be satisfied if this is the end of the line. Scott has engaged, over and over again, with the factual scaffolding of Alexandros' arguments. The 5-10% chance is an adequate conclusion. Let Pascal and Omura wager accordingly.
Thanks, I hadn't noticed that phrase!
"Realistically, this project was outside my expertise and competence level."
FWIW I've thought about that piece a lot this last year, and the object-level "worms break science!" point wasn't what most changed my epistemology. The general importance of turning contrarian views over in one's mind dominated my thoughts and how I discussed this with others.
It was a winning item for me in one-on-one discussions with thoughtful people about contrarian ideas, and how such ideas might be wrong in subtle ways that require thorough analysis, and how herding on this stuff has some risks. It provided a great way for me to evangelize about about how politics is the mindkiller without just talking about politics being a mindkiller and wearing everybody out with it.
"C+ for results"... When you're trying to improve on what's out there, you get to grade yourself on a curve relative to baseline, not on whether or not you saw the pure true center of the universe unfiltered. What's your grade relative to the next best take on this topic?
"Realistically, this project was outside my expertise and competence level."
So help me. If you shy away from these sorts of investigations in the future because you think you overreached here then humanity is doomed. If this implies any risk of self-gatekeeping, please ask yourself if we are better off leaving this to the next best available substitute.
Prompt: Please rewrite Yeats' The Center Cannot hold, but make it about Scott Alexander of Astral Codex Ten worrying that he didn't write a good enough essay because it had some errors and overextended a conclusion, when he in fact wrote the most thoughtful essay humanity produced on the topic.
"The mind of Scott Alexander may falter,
Worried that his words fall short,
But in truth, his essay stands tall,
The most insightful written in all sport."
"The doubts may come, the fears may rise,
His confidence may seem to fall,
But the center holds, for in his eyes,
Lies the most profound thoughts for all."
"For he wrote not just with pen and page,
But with the wisdom of the ages,
A work of art, beyond compare,
A gift to humanity, with care."
"So let not Scott Alexander fret,
For his essay shall forever stand,
A testament to his talent and intellect,
The greatest written by human hand."
I hope you're blushing and you hate it. :P
Ha, rereading that poem is so mid and over the top, even for chatgpt, it probably backfires and undermines my point. But it's fine, we're all big dorks deep down and awkward imperfect things are beautiful. Sometimes we can just wabi sabi some shit and it's fine.
What could compel someone to expend this much effort (twenty-one parts) other than participation in culture war?
Alexandros blocked me on Twitter long ago just for asking whether there was one good RCT supporting ivermectin. He apparently runs a startup, yet has the time in just a few months to write a series of posts that total over 86,000 words (a sizeable non-fiction book!) just to respond to ONE blog post from Scott. And everything he wrote was completely predictable in advance. If a study was pro-ivermectin, he was going to defend the study to the death; but if it was anti-ivermectin, then he was going to nitpick it to death.
That's not why I blocked you. The reason I blocked you is much the same as the reason you were banned 3 times from theMotte subreddit for responding to me with ad hominems and insults.
I won't be entering a debate with you, so feel free to respond in whatever way you like.
Not true. There were no ad hominems or insults in that Twitter exchange. You blocked me after I had done literally nothing except ask for one good study (which you mocked, after which I said that a better answer would be just mentioning one good study, if there were any). https://substackcdn.com/image/fetch/w_1456,c_limit,f_webp,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2Ff08ee13f-d59f-4ffa-82af-1bb6e6b9685a_550x787.png I was baffled at the time, because I've almost never been blocked by anyone, and certainly not for just asking for a good study.
The Reddit exchanges came later. At that point, I had become frustrated due to our exchanges over a Marik study where you were clearly in the wrong, but refused to admit it, and I had to laboriously explain to you why it is important to have a constant denominator (and what a "denominator" even is). At that point, I had given up an earlier belief that this was a good faith discussion -- what sort of person pretends not to know what a denominator is (or else just changes the subject)?
Interesting to see that Alexandros' heroes and affiliates are now promoting ivermectin for other infections as well, not because there's any evidence but because of . . .
well, who knows.
https://www.washingtonpost.com/health/2023/02/26/ivermectin-use-covid-flu-rsv/
Another area of disagreement seems to be about Gideon, why do you two disagree on his trustworthiness?