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"I know I’m two months late here. Everyone’s already made up their mind and moved on to other things."

Fastest click I ever clicked on one of these posts.

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Right off the bat I learned pored is spelled differently from poured, so strong start to this post.

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"I'm not going to watch it, because it is a video..."

You don't watch videos?

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"But I don’t really know how to do that, and any speculation would be too political even for a section titled “The Political Takeaway”. I would instantly kick in an extra month's subscription fee to read this.

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So, 85-80% confidence of less than 30% mortality reduction does in fact represent a major crime against humanity in your estimation, I would think? Expected loss of lives is well into the hundreds of thousands.

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Scott, long-time lurker here. My antivax, anti-public health elite uncle is currently taking ivermectin for his long COVID, at the behest of his nutty physician's assistant (he fired his doctors, who wouldn't prescribe him things like ivermectin when he had an active infection back in December 2020). I asked him to explain how ivermectin could possibly treat both an active viral infection *and* the damage to his organs he's experiencing in the medium-term aftermath. He was flummoxed.

He later came back and said that the PA's theory is that parasites "acted up" while his body was fending off the virus, and that parasites are causing his respiratory and digestive issues. Mind you, he lives in a wealthy part of Southern California, not Bangladesh. Has anyone ever made the case that long COVID = parasites? I don't know whether to laugh or cry.

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Great read, thanks

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Writing this while about 1/3 of the way through reading...

A) Thank you so much for doing the yeoman's work to read through these carefully. This is what we pay you for (/s, lol)

B) Regarding Babaloba et al, I tentatively think I may have found the solution:

(This is the context)

"I think his point is that if you have 21 people, it’s impossible to have 50% of them have headache, because that would be 10.5. If 10 people have a headache, it would be 47.6%; if 11, 52%. So something is clearly wrong here. Seems like a relatively minor mistake, and Meyerowitz-Katz stops short of calling fraud, but it’s not a good look."

We have four columns - 1 for treatment A, B and control each, plus an overall. This allows us to triangulate to see what has happened with the data.

Column A is the mystery - how do you get 50% of 21 people, and so forth? Easy, have K people who have missing data for this outcome. Happens all the time. (In my research, I deal with much larger samples, but there's always missing values for some trivial % of the data). Technically you can have different numbers of missing by variable, but the easiest solution to make (at least a few) of these numbers work is to allow 1 person with missing data in Column A.

Then we have 6/20 with fever, 10/20 = 50% with headache, and so forth. Columns B and C look fine. Ok, the question then is does my "fix" give the correct totals in the "overall" column? Turns out that (as far as I checked, it does)

Details:

Headache: 10/20 in col A, 12/21 in col B, 5/20 in col C. This would give 27/61 overall, which is 44.26%, which matches their 44.3% exactly.

Fever: 6/20 in col A, 9/21 in col B, 4/20 in col C. This would give 19/61 overall, which is 31.147%. They report 31.2%. This *doesn't quite match*. But if you round to 2 dp, you get 31.15%. And then if someone later rounds to 1 dp, you get (incorrectly) 31.2%. I bet errors like this happen all the time - you have your software print the result to 2 dp, and then as you write your table, you decide to do 1 dp and every time you have something end with "5" you don't go and check which way the raw data should round. (I bet I make this mistake in my research all the time when rounding coefficients and so forth manually in text, because who always remembers to stop and check?).

Haven't checked the other variables, but getting these sufficiently close matches for the first two I checked for the most simple "non-fraud" explanation of "1 data point missing" seems too much of a fluke otherwise.

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The alien / vaccine hypothetical is compelling, but what's missing is that IRL all humans would have 7-12 different alien chips already in them and are objecting to getting another.*

*Yes yes mRNA is a new tech but you don't see anti-vaxx people being willing to get non-mRNA vaccines.

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A few random thoughts:

It would be great to see analysis of why a deworming medicine is thought by some medical professionals to be an effective treatment for a respiratory disease.

What could possibly motivate the folks at ivmmeta.com to spend so much effort in creating and maintaining such an impressive site? I see only two candidates - sincere belief in the effectiveness of Ivermectin or a profit motive. I don't believe trolls or nihilistic fraudsters would have that much motivation. Since the drug is already a generic drug, it would seem the profit motive is less likely than a sincere belief that it is an effective treatment for COVID19.

I don't understand the intensity of the establishment backlash against Ivermectin. I have not seen evidence that vaccination rates would be higher if people did not believe ivermectin worked. Nor do I think that it's intuitively clear that this would be the case. People who distrust the establishment don't trust them on vaccines or on whether or not ivermectin works. Even if they were somehow convinced that ivermectin didn't work, they wouldn't trust the vaccines unless the public health establishment suddenly became more trustworthy overall. Add to this the fact that if taken in human sized doses, ivermectin is safe and I don't really see the reason for the virulent mainstream backlash. In fact, the backlash probably cost some lives by causing people to take crazy dosages.

More generally, I don't understand the establishment messaging of vaccines (+masks) or you're the worst. There are plenty of other ways to reduce risk including doing things to maintain or improve overall health (exercise and sunlight). And these activities are not mutually exclusive with taking vaccines. The messaging should not have been anti vaccine alternative - that just spreads distrust. It should have been vaccines are good and here's a bunch of other positive steps you might take to reduce your COVID19 risk. And the evidence for ivermectin is mixed, but if your doctor wants to give you some, whatever its harmless. Again, I think the vaccine or bust messaging was really counterproductive.

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This is the single best article written on ivermectin throughout the whole pandemic. Thank you.

I've been looking at ivermectin since the early months of the pandemic. I had heard of the I-MASK+ protocol when people were still using ventilators on COVID patients (with an 85% death rate in NYC), and it sounded really promising to me. So I've been really open-minded as to whether or not it actually worked.

But over the next several months, and now 18+ months later, it never really succeeded in having a home run in terms of proving that it worked. I don't think we need medication that decreases viral load 3 days faster, we need medication that keeps people out of the hospital and from dying. It was pretty clear anecdotally that ivermectin wasn't doing that.

I think basically it comes down to the fact that when you have a disease where 85% of people suffering no or only mild symptoms and 0.5% death, it's going to be a very hard disease to determine if a treatment worked or not.

I think the science we have been doing over the course of the pandemic has been largely garbage because we haven't learned anything to help us whatsoever since March 2020. If I remember correctly, the mRNA vaccine was designed within days of the virus being sequenced in January. The rest of the time on the vaccine was spent making sure it was safe, but you can argue that nothing new was learned after the vaccine was created. Since then, we haven't really learned anything about the virus, about the transmission, how to fight it, etc. Our best bet is to wear masks and stay outdoors, which we already knew.

What we as a species really need is a global mobilization of scientists, where a single global committee designs a thousands of different experiments that would help us narrow down how the virus works and how to fight it, and divvy up the work globally. We could have worked in parallel doing thousands of experiments to help us figure out what exactly we need to do to beat COVID, but instead the millions of scientists around the world were trying to determine if SARS-CoV-2 was found in vaginal fluid or semen.

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Great read, Scott. You moved me from the “IVM probably works a little” basket to the “IVM probably doesn’t work” basket.

I do think there’s a few points you could add to your analogy that seem fairly important to the more educated and knowledgeable vaccine hesitant people I know:

- Previous brain implants have gone through long trial periods to ensure they don’t cause adverse effects. However, the aliens believe the quantum memetic plague constitutes an emergency and there isn’t time for such a process. Plus they say the early trial results look great.

- The first implants start getting inserted and some rare side effects are noticed. In the worst cases, some of the implanted die as a result. The aliens insist there’s nothing to worry about, as it’s a very rare occurrence. But you can’t help wondering if they’re investigating the problem in good faith.

- A few months into the program the implants stop working as well as promised. The memetic plague has mutated, and found new ways around the implants. The aliens acknowledge this but maintain it changes nothing of practical importance. Herd immunity to the memes may no longer be possible.

- Anyone promoting vaccines in public is censored. On some platforms, even non-promotional discussion of vaccine efficacy is targeted.

- A few more months pass and the aliens decide that implants will be mandatory, and refusal will mean you cannot use any alien technology! Alien tech has already permeated all of earth life. They’re also implanting children, who were supposed to be almost unaffected by the memetic plague. The brief explanations are difficult to parse, and seem somewhat circular to the human mind.

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This is an incredibly valuable post. Thanks for doing the work that all the people whose job it was didn’t do!

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The fluke/fluke "coincidence" is the clearest proof I have ever seen that God made the babelfish.

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Great read... you must have a nuclear reactor mod for your brain, I can't imagine having the energy, time and focus to write these pieces, but I'm grateful that you do. You're probably the only person I trust at this point to do a fair analysis.

This also brought to mind a well circulated Twitter thread which summarizes some of the same sentiments: https://threadreaderapp.com/thread/1422181544161128450.html

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This is your best post in a long while!

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Sorry…50% of Americans are young earth creationists? Can you provide some data on this?

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I wonder if this is the type of thing that you might cover in an epistemology/philosophy of statistics class. Every time I see something like this I just end up more and more confused about what kinds of reasoning is legitimate, and when does statistical evidence actually point to the conclusions that it naively says it does.

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Great article, thank you! But I really wish you got the worm hypothesis advanced enough, in your view, to feel more than 50% confident that worms are a significant confounder.

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Before your months late entrance into this, I recall looking up who maintained this site. Since I did that, I have associated it with the FLCCC Alliance.

Tonight, when I went to icann whois, the first auto text suggestion was for ivmmeta.com. I recall finding that it either shared a server or owner with FLCCC.

Caution, my memory may not be serving correctly:

I may have looked up information about FLCCC the same night, but I am quite sure my inquiries were at different times.

I may have connected them, because the "meta" and "C19" sites link to FLCCC.

I don't remember enough detail to give to say definitively what it was I saw that made me sure of a connection.

With the caveats out of the way, I will say I have high confidence that this site is indeed related to the Alliance.

But most alarming in my view is that there are identical sites for HCQ and Vitamin D. And the analyses appear to show similar levels of effectiveness as IVM.

I've been called both a BigPharma apologist/corporate shill and a pinko by anti-vaxers since the pandemic started. I'm certainly much closer to the latter, but it illustrates how generic heuristics can override judgement by otherwise rational people.

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This whole thing was really excellent, but it does give me an opportunity to ride one of my hobby horses:

Steinbeck's "temporarily embarrassed millionaires" quote was not an explanation for why the poor did not join the communist movement, but rather a sorta self-deprecating description of those who did. In other words, he was complaining about the champagne socialists who were in the movement, rather than aspirational workers who were not. https://en.wikiquote.org/wiki/John_Steinbeck#Disputed

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Scott, I really appreciate this careful review of the data on ivermectin. While it mostly matches what I already thought about the subject, it presents it much more clearly and carefully than anywhere else I have seen.

Which is why I'm so baffled that you are so confident that the covid vaccines are safe and effective that you don't even feel the need to present an analysis of the studies on the subject, and instead went with this analogy about aliens. Even though the Pfizer study to get FDA approval was just shown to be partially based on falsified data, and the all cause mortality was higher in the vaccine arm than the placebo arm. Even though the trial for children 5-11 did not show any clinical benefit at all (because no one had any serious outcomes in either arm). Even though no one has demonstrated any population level association between vaccination rate in a state or country and covid rate.

I really, truly wish I was as convinced as you seem to be that the vaccines are safe and effective. But it doesn't match my personal experience, and what I'm seeing in the world around me. I know that one shouldn't base one's epistemology on personal anecdotes, but I haven't found the studies on this subject nearly as reassuring as I would have hoped. I see everyone dismissing the sudden spike in VAERS reports because causation can't be proven--but why would the rate of reports suddenly increase so much compared to previous vaccines? All the papers I've seen about VAERS prior to covid suggest that it almost certainly underreports the true rate of adverse events from vaccines rather than overreporting them.

I know it's a huge, probably impossible ask, but if you could find the time to try to dig into this subject, I would be truly, deeply grateful. I want to be convinced, and I believe that I can be convinced that the vaccines are safe and effective (I actually am vaccinated, but based on the research I have done since then, I regret it and don't want to get the booster). I see vaccine denialists making obvious errors and exaggerations, but I also see them pointing out what seem to me to be serious flaws and shortcomings in the studies supporting vaccination. I'm not saying I think the vaccines are definitely unsafe/ineffective, but especially for young healthy people who are at low risk for covid, I'm not seeing the convincing case that getting vaccinated is statically a good idea that I would like to see, especially considering the many places that are now mandating them.

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"Putting aside the question of accuracy and grading only on presentation and scale, this is the most impressive act of science communication I have ever seen." -- surely something that can make you confident that you have learned something true when in fact you have learned something false is *bad* science communication even if the information is accurate, right? One takeaway from this post seems to be that this kind of chart isn't a good way to communicate science even when the underlying claim is true, because it provides a false sense of confidence and promotes a common misunderstanding of how progress in science actually works ("just take all the effect sizes from the papers and put them together without stopping to understand all the underlying science / which papers you can trust / what sorts of evidence experts are used to seeing for claims that turned out to be false /etc.)

"Can something have a p-value less than 0.001 and still be a fluke?"

Yes of course!! P-values only measure the probability of flukes under the null hypothesis assuming everything went exactly according to plan. But there are lots of boring flukes (a table got mixed up somewhere in the data entry process, the randomization got screwed up in a way the balance tests missed, a doctor felt bad that these patients were on a deworming drug for a virus and slipped them antivirals, etc.) that are unlikely but not "literally one in a thousand" unlikely.

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Scott, and anyone else, what makes you so confident in the COVID-19 vaccines? Have any of you looked at the data for them after the past year?

Under the "Political Takeaway" section, you write this:

"But the basic issue - that the vaccine works really well and is incredibly safe for adults - seems beyond question. Yet people keep questioning it."

I'd love to stop questioning it, really, but I can't see the raw data. And neither can you. As a fellow human, the aliens have all this sophisticated and powerful technology, and a year+ of data of the new tech being used "successfully", however they won't share it. They've locked it all up in vaults that only their peers can access, and whenever I ask for where I can go to view the data, they refer me to VAERS (an unreliable, under-reported and discredited database). They then go on to discredit it themselves and assert their belief of how only they can ever really know what the data means.

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You have gone pretty hard against cluster randomised trials!

"This was “cluster randomized”, which means they randomize different health centers to either give the experimental drug or not. This is worse than regular randomization, because there could be differences between these health centers (eg one might have better doctors who otherwise give better treatment, one might be in the poor part of town and have sicker patients, etc)."

The same argument could be made against individual based randomisation, eg "there could be differences between these individuals (eg one might have chronic diabetes and do poorly, one might be in excellent health and do well)".

Cluster randomisation and individual randomisation are basically the same except that the denominator in a cluster randomised trial is not the number of individuals but the number of clusters (the unit of randomisation).

There are situations where doing cluster randomisation *is* the best thing to do, for example when you think there could be interactions between individuals in the clusters (the example I have in mind in mass drug administration for an infectious disease, give it to a whole village - the cluster - and you can wipe it out, whereas if you give it to individuals at random they can then re-infect each other).

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Couldn't agree more on summary point #3.

Somewhat related story: for a class I was messing around with data from the COVID-19 School Data Hub and found out that their preliminary write-up on Virginia (https://www.covidschooldatahub.com/preliminary_research) had a pretty big flaw. Emailed the researchers and they said I was probably right!

Essentially it's Occam's Razor (paraphrased): stupid mistakes are much more common than conspiracies or manipulation

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Big Parasitic Worm strikes again!

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I thought it was a really good article! As a lay person, getting to go inside of the mind of someone with a more trained eye for evaluating scientific papers was helpful.

I will say that your comment "half of Americans are young-earth creationists" (I assume you are talking about Christians in general?), while possibly true but also feels like a straw man, may also breed the same mistrust to certain readers as in your analogy of the humans to the hostile aliens. It kind of cheapens what was one of the main points of your article (or as I read it): Don't talk down to people.

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I think it's worth mentioning that helminths are a bigger problem in the US, particularly the South, than is commonly known. Enough so that it could be a relevant factor in studies here, IMO.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847297/

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Great post! every time I see work like yours, my faith in humanity increases. Taking such a deep dive in such a divisive and already not-so-relevant topic (given availability of actually working therapeutics like dexamethasone and fluxovamine, not to mention new Pfizer and Merck drugs) just for the sake of getting things straight - that's admirable!

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What we see with Covid is that people who refuse to get the cybernetic brain implant are still going to the hospitals run by aliens once they experience symptoms of the quantum memetic plague. If you trust aliens/doctors enough to treat you when you're sick, you should trust them enough to get the vaccine.

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> although rationalists did no better here during the early phase of “looks promising so far” than anyone else

You sure? I have the sense that people in the LW orbit were much more likely to say "we don't know" than the placebo group of smart-sounding people on Twitter. Don't know how I'd go about quantifying that, though.

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Overall a great article!

For the worm hypothesis, you could find some interesting evidence for it by looking at the IVM prophlyaxis studies. If the IVM only lowers severity by avoiding hyper worm growth, it should have basically no effect on preventing getting a COVID case. Triangulating the evidence would probably strengthen your case, would you try that out or read an analysis of that? OTOH it would be puzzling otherwise. The prophylaxis results are at the bottom of this table https://ivmmeta.com/#fig_fp .

Perhaps reconsider including Mayer et al. Or rather, given the potential for that choice to swing your analysis, you might take more time to consider your logic on excluding it. Yes it is not an RCT. But the point of RCT is to even out factors among both groups to not favor either the control or the threatment. It's highly improbable for obese, diabetic, many other co-morbidities IVM group to outperform, given even one of those conditions increases hospitalization / mortality risk around 1.5 to 2x (from my fallible memory). P(results | ivermectin is working in high parasite places AND Argentina is a low parasite place) should be quite low yet the results are more improbable than the unadjusted p value p<.03 stated in the post. Is an adjusted analysis where they regress to mostly remove those differences, more informative for that probability i.e. "risk of death, 55.1% lower, RR 0.45, p < 0.001, treatment 3,266, control 17,966, adjusted per study, odds ratio converted to relative risk, multiple logistic regression, Figure 3." ?https://c19ivermectin.com/mayer.html

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Sorry, not on topic, but why have the default avatars suddenly changed such that so many people are getting the same few? It's confusing.

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I can't see that others have pointed this out yet. The analysis linked in Avi Bitterman's tweet, which looks at the effect of ivermectin in regions (of high, medium and low prevalence of Strongyloides) doesn't actually find a significant difference in risk between those subgroups (p=0.27). That is, there isn't evidence that there's an interaction; that it's effective in places with high prevalence but not effective in places with low prevalence. The effect in the high prevalence regions individually is also barely significant (p=0.02). This is an example of the idea which Andrew Gelman popularised, that 'the difference between “significant” and “not significant” is not itself statistically significant'.

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This was a much better and more important post than the title led me to expect. The last few sections are Toxoplasma-of-Rage-level good. (Parasitic infections bring out the best in Scott, apparently.)

The argument about filter bubbles and aliens goes further than it needs to, though. Scott seems to be trying to steelman Ivermectin support as a dry epistemic determination when it's clearly motivated reasoning. Ivermectin enthusiasts want it to be a good treatment because they don't want to take the vaccine. They don't want to take the vaccine because it's a Boo Red Tribe button. It's a Boo Red Tribe button because it got politicized. Also, the aliens in that Red Tribe view aren't immunologists, but the political and cultural elites whom they (somewhat correctly) model as being willing and able to control the narrative of What Immunology Says.

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Another really brilliant post. I think your metaphor is excellent.

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Wow. Now that you lay it out so clearly, I wonder how this hasn't been part of the standard story about Ivermectin since day one? "It doesn't do much against Covid on its own, but it *is* a good dewormer; getting Covid while having a worm infection can make the Covid more dangerous, so people who get Covid while they may have worms can benefit from taking Ivermectin". It seems so obvious when you put it like that.

Surely the people who did those studies in areas of the world where worms are endemic, would have been aware that probably a lot of the patients in their study groups had worms, and that therefore Ivermectin being a dewormer probably had something to do with its effectiveness? Wouldn't they check for that?

In the summary, Scott writes "Parasitic worms are a confounder in ivermectin studies." Wouldn't another valid conclusion be "Ivermectin *actually does work* to reduce Covid symptoms, in the subset of patients who happen to have a parasitic worm infection? Which may be a nontrivial percentage of patients, depending on which area of the world we're talking about.

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Of course, one crucial question here is: how is the alien-brain-implant skeptic going to react when the aliens go "Okay, to hell with you rubes, we're going to mandate the brain implant as a condition for going to work (or going to a bar or a sports game etc.)"?

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I reached the same conclusion without doing any analysis of the data. But it’s reassuring to see the the experts agree with me. Paradoxical parasites explain the significance of tropical effect. Tiny.one/clotstop

sincerely

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Fantastic post!

Minor point - ‘Do forest plots to find publication bias’ should be funnel plots.

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I appreciate the depth, but it doesn't engage with a few arguments that proponents make and groups studies together in a haphazard way. Possible defenses include that IVM works much better when given early or as a prophylactic, and that many negative studies enrolled the patients pretty late.

Also that epidemiological evidence in India and a few Latin American countries suggest a strong effect for IVM.

Not sure either way, but so far I have not read ONE article, either by proponents or sceptics, that differentiates studies by time of administration and endpoints. Personally, I think it's likelier than not that it doesn't work, but given the safety profile I would still take it.

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Really not a fan of the alien analogy, I find it insulting by implying that those who are skeptical of the prevailing narrative around the Covid vaccines are only doing so out of reflexive distrust of "science" and big pharma. If I genuinely thought that the vaccines were as safe and effective as they were purported to be I wouldn't disbelieve them out of some tribal reason. I was rooting for the vaccines, ideally they really would have "got us out of the pandemic".

About the vaccines - i have no idea how you can reach the conclusion that they are "very safe and effective" - here are a few things that poke holes in that conclusion.

1. High vaccination rates having no correlation with low case rates. Many countries or cities with high vaccination rates are seeing explosions in cases

2. Several studies that show waning vaccine efficacy over time, both for prevention of disease and reducing symptoms

3. Excess mortality being higher this year in many countries where vaccines were rolled out compared to last year.

4. Consistently much higher rates of adverse events recorded in monitoring databases such as VAERS ( And is the case over many different countries )

Not that this is a black and white picture, I do think that the vaccines seem to reduce mortality for Covid, but the question is how long for and if there's anything else that we could do to help those who catch the disease in addition to vaccination.

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The reveal on this post was one of the most satisfying intellectual experiences I've had in years. It was so obvious in hindsight I actually physically slapped myself on the forehead.

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I've been thinking a lot about what to replace "trust the science" with. We have this compulsion to over-fetishize scientific form (p-values are a weird, barely useful social construct in a world as nebulous and interconnected as ours) precisely to defend against an outside view problem where low-effort conspiracy theories look exactly the same as correct contrarians without doing a lot of work to sift it out. But when you think about fraud from a institutional lens a la Davies's Lying for Money, you can see that "what matters is where it came from!" as a position is tailor-made to let people cash in on the form as a free credibility signal. The cranks are great at throwing in stats words now, and have been for a while.

To think about the way forward, it's worth making the ethnomethological flip (https://metarationality.com/ethnomethodological-flip). That is - how do the people who *are* right actually *do it?*? I'm a temporarily-embarrassed immunologist too, and I was the one who warned all my friends about COVID-19 in Feb '20. I wasn't reading studies and I wasn't calculating p-values. How did I know anyway? Well, because I followed Zeynep Tufekci and a lot of Hong Kongers and had an easy time putting the pieces together. But conspiracy theorists are also great at writing little stories to explain anecdotal evidence. You can say in principle that relying on anecdote here doesn't work because there are also anecdotes about FEMA death camps. But do the flip; I DID believe the good anecdotes, and I didn't believe the bad anecdotes, so it's clearly possible somehow and that somehow doesn't involve math or probability.

This has been my research area for a few months and I suspect that a lot of the secret sauce is ontological. Ontologies can't be *right or wrong* but they can be *better or worse*, and we're not really used to talking about them in that way. So I think people end up talking at cross-purposes a lot because some people are Just More Likely To Be Right because they're using a more sensible ontology, but we don't have the language to make that claim. So we can try to assume that "using a better ontology" and "following proscribed scientific norms" are the same thing - and they probably match above random chance - but there's plenty of cases where it's not true which gives cranks all the ammunition they need.

The slogan ought to be something like "trust the most sensible ontology", but we have scads of really urgent work to do on helping people determine sensible ontologies. And this work historically has been done through mentorship which is why things feel so distinctly odd nowadays.

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One idea that came to my mind is that instead of "trusting science" people can "trust scientists". Specifically, we can poll all scientists to learn what the scientific consensus is. This will presumably avoid the issue of "trusting experts" where only a select few most loud personalities get a say.

Imagine a Wikipedia-type site where you could find the surveys of the world scientific community on lots of issues, what do they agree on and what do they disagree on, classified by specialty and country of origin, and tracking the change of sentiment over time. If you're interested, I wrote more about this idea on my blog: https://www.see-elegance.com/post/making-consensus-legible

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I don't know about anyone else here, but I grew up hearing about ivermectin from radio and TV ads like this one:

https://www.youtube.com/watch?v=QGbZKlbjNCo

My scepticism about it being a miracle cure for Covid is partly based on the following - warnings when dosing cattle either by pour-on or injection that it is not to be used in animals producing milk for human consumption:

"Animec Pour-on for Cattle is used for the treatment and control of gastro-intestinal nemotades, lungworms, warbles, chotioptic and sarcoptic mange mites and sucking and biting lice of beef and non-lactating dairy cattle.

​Active Ingredient:Ivermectin

Target Species: Cattle

Treats and Controls: Gastro-intestinal roundworms, lungworms, eyeworms, mites and lice

Administration Method: Pour-on

Withdrawal Time: 28 days for animals intended for meat and offal, Not permitted for use on animals producing milk for human consumption.

Signs and effects of infected livestock

Infection:Gut Worm

Symptoms: Diarrhoea, decreased appetite, loss of weight

Effects: Gutworm can cause severe damage to the stomach and small intestine which will cause parasitic gastroenteritis, this will not only negatively affect the health of the animal but will affect the profitability for the farmer.

Infection: Lungworm

Symptoms: Short, sharp cough that becomes worse with exercise, in severe cases the animal will have obvious difficulty breathing.

Effects: Lungworm infections cause a high susceptibility to respiratory viruses and bacteria. Infected cattle are prone to contracting severe bronchial pneumonia which if left untreated can lead to death."

And partly because I do not see how something that is mainly a wormer cattle drench is going to be a great anti-viral. Maybe it is! In vitro - which is a hell of a lot different than in vivo.

My position has always been that the good results came from trials in places where, as Scott points out, people are prone to worm and parasite infestations. My totally untutored guess was that the ivermectin treated parasites, which took strain off the immune system, which gave back capacity to fight Covid, and so yes treated patients did better than untreated.

But if you really want to inject or swallow or pour on ivermectin on yourself, I still think your best option is to be a cow in a field.

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One sociological question this triggers for me is why are there so many of these terrible studies from strange people testing invermectin? Is it just thet if something is in the news a lot then people will do stuff related to it to try and make a name for themselves?

Which then leads to the secondary question of why people started asking about invermectin in the first place. My level of charitability to the studies would vary a lot based on whether it was a) because some sensible doctors had a plausible method of action by which it would fight viruses b) someone chose it randomly from a hat c) people who sell invermectin, or in some other way make money off it, started promoting it.

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I want to plug my heuristic for deciding not to use Ivermectin -

1. The government DOES NOT WANT YOU TO DIE. They are not lying to you!

Even if you suspect the political class of lying, people underestimate the competency of the many bureacratic organizations full of scientists and doctors in a time of crisis. My mental model is they are nerds just like engineers - they are interested in truth, not politics.

They were called upon in a crisis. I am absolutely sure they did their best as a whole, and I am absolutely sure the best of them will forget more about medicine and statistics than I'll ever know. Deep competence acquired over years is real, and no even dedicated amateur science by smart people is not a substitute.

Personally it was clear to me that e.g the urging not to use masks was driven by fear of shortages. That was a lie, but not enough of a lie to make me distrust the entirely of institutional medicine like wow calm down.

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The PRINCIPLE trial is a large scale RCT in the UK is investigating ivermectin. Given that it is in the UK, it shouldn't suffer from parasite-related confounders.

I'll bet you 150$ to $100 that it shows a weak but positive result for ivermectin. I don't mean in the sense of "statistically significant", but in the sense that "average days to recovery ivermectin" < "average days to recovery non-ivermectin", if they don't measure average days to recovery we can pick another indicator. If ivermectin had no effect the probabilities should be 50-50 (under reasonable assumptions on the noise) so this bet would be positive expected value for you.

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It's articles like these that... well... greatly reduced my confidence in "studies say" and "SCIENCE"!!!

I did a bachelor of science and thoroughly enjoyed it, but I got to spend a lot of times with scientists and it shattered my childhood illusions of noble men in white coats with a rock solid commitment to follow the truth wherever it led.

The original pro-inver compilation looked fantastic until a veritable firehose of fisking was turned upon it ... but the only reason the firehose got turned on was an epic load of political motivation. I generally trust Scott because he writes like a standup guy, so I'm happy to accept his fisking, but I bet if there was another standup guy out there who started fisking his fisking I'd end up scratching my head again.

I'm not anti-vax or pro-inver so I say great - fisk on Scott! But what other steam piles lurk out there that haven't attracted the firehose yet that I'm smugly confident in?

As the years roll by, I'm becoming increasingly aware that there is about 3 men and a dog who are interested in what is true and damn the torpedos, full speed ahead.

If creationism or race science turned out to be true, who here would actually legitimately want to know if there was a chance their social circle would find out they knew it?

I'm not ready to toss science because I can see a bunch of great stuff it's delivered... but boy are my days of making authoritative scientific pronouncements in the lunchroom are behind me.

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"If we want to make people more willing to get vaccines, or less willing to take ivermectin, we have to make the scientific establishment feel less like an enclave of hostile aliens to half the population. Do that, and people will mostly take COVID-related advice, for the same reason they mostly take advice around avoiding asbestos or using sunscreen - both things we’ve successfully convinced people to do even without having a perfect encapsulation of the scientific method or the ideal balance between evidence and authority."

Purely hypothetically, do you honestly doubt that if certain IDW influencers randomly decided to gin up sunscreen or asbestos-removal opposition as a culture war issue, then we wouldn't subsequently see widespread opposition to sunscreen and asbestos removal among their followers? People might even start mocking the weirdos who randomly decided sunscreen is anti-American, at which point this vicious condescension would be all the proof anti-screeners need that elites look down on them and their values, further entrenching sunscreen opposition as an essential pillar of their identity. These grievances and suspicions aren't fixed essential flashpoints that can be traced back to significant divisions in the tribes and their values. They can be turned on and off like a light switch, especially thanks to a relatively new insatiable economy of culture war influencers chasing clicks. (As others have pointed out, many holdouts were fine with mandated alien implants until less a year ago, others have argued that mRNA vaccines are actually *new* and that's what makes them alien and suspicious but that doesn't change the fact that very similar implant *mandates* were just an assumed normal part of life explicitly defended by conservatives like Ben Shapiro and the Federalist and now overnight mandates became unconscionable tyranny.)

The entirely alien analogy suffers from a flaw that emerges in a lot Scott's writing where he seems to just assume the Blue Tribe and its aligned elites are the prime movers of these dynamics and on some level nearly all polarization and animus emerges from what they do or don't do (and subsequently how the Red Tribe has to helplessly respond in kind), completely ignoring the fact that the Red Tribe actually does have an agency all its own to play offense in the culture wars. It's like seeing a Hatfield attack a McCoy, then witnessing a McCoy attack a Hatfield in retaliation, then writing 10,000 words about how the Hatfields started this whole thing and they really need to learn to be more charitable to the McCoys and take their grievances seriously. The Hatfields might well have started it but that's a hell of an intractable, difficult question that can't just be assumed because that's the first attack you saw or you feel some collective guilt as a Hatfield yourself.

Is there anything in the alien analogy where anti-alien famous people confidently, loudly pronounce that quantum plague memetic deaths will remain at zero or hold steady at like 15 cases, then at one point 3000 people start dying of the quantum memetic plague every single day? Or how about anti-alienists compulsively repeat debunked canards about how actually the quantum plague is no worse than a common tachyonic sinus infection with a 99 percent survival rate while ignoring the inherent risk of unknown memetic plagues having unknown long-term consequences while *simultaneously* arguing the the memetic plague is actually a fiendishly designed bioweapon that the aliens are deliberately deploying to wipe us out? What if anti-alien media outlets start encouraging anti-alienists to harass and intimidate aliens and the people allied with them by calling the cops on people they see wearing memetic plague blocking space helmets. What if in addition to trumpeting the (human created) vaccine, anti-aliens had also aggressively promoted ginko, ginseng, forsythia, and oleandrin as cures for the memetic plague *before* they ever settled on the ambiguously effective human vaccines as their go to miracle cure? (I mean these as all as honest questions as my adhd forced me to kind of skim the last section and I may have missed something) Would you still say they were basically being reasonable if using flawed reasoning? If all these things had happened as a human I might still have my suspicions of the implants but( if my identity weren't completely emotionally wrapped around anti-alienism) I'd have to admit that my fellow human alien skeptics had behaved far worse and gotten more wrong than even the smug imperious aliens. It's one thing to interrogate the myriad failings of scientific elites, its something else entirely to do so while seemingly ignoring the record of even worse miserable failure and arguably unprovoked culture war aggression that emanates from the opposition to medical/scientific elites. It's something that looks a lot more like rationalization rather than rationalism.

I think I understand at least some of the inchoate anxieties that drive people to vaccine opposition or Ivermectin boosterism. I've struggled with crippling anxiety, sometimes about unknown chemicals, my entire life. I also live in a fairly conservative area and I've had two people I respect and care about approach me and vent their vaccine fears and subtly ask me for advice, which vaccine I'd gotten etc. Imo just on that small sample size there are some relatively organic fears (as opposed to the ginned up ones) that are far stranger, somewhat a-partisan, and in weird way deeper rooted than just these particular noisy culture war flare ups between medical elites and IDW influencers. I get that all Ivermectin boosters and vaccine skeptics aren't necessarily the worst Joe Rogan types but I think we very nearly approached a limit where the persuadable Fauci-skeptics have already bitten the bullet and gotten vaccinated and what's left just isn't very amenable to reason.

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Typos:

- "Babaloba et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakoloko”" -> "Babalola et al: Be warned: if I have to refer to this one in real-life conversation, I will expand out the “et al” and call it “Babalola & Alakaloko”" (two misspelled names)

- "mispelled as “Profesional Medical Journal” in its URL" -> "misspelled", though possibly intentional

- "which will lead to them having making good health decisions" -> "which will lead to them making good health decisions"

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Long time reader, first time called.... Whats the battery life of these alien implants like ?

Seriously though, that was an awesome deep dive and analysis!

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The citation link for Gluchowska et al is missing. Presumably it's this paper? https://doi.org/10.3390/jcm10112533

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"Trust Science" is definitely not the right approach. It will devolve in in-group vs out-group. However, simple explanations of underlying truths are much more effectively convincing. In this very article, a simple paragraph, explaining that worm prevalence confounds positive results for ivermectin, did more convincing that all those individual and meta-analyses discussed previously.

Explain the Science! People require a "why" they can understand. Ivermectin works against COVID. Ok. Why? What does it do the virus or the body? Without a clear answer to that, statistics and data are hopelessly getting in the middle of the perpetual cultural warfare.

Honestly, I would be disappointed to learn that "how and why does this drug work" is not the first thing, before even reading a single paper, that doctors consider before deciding on whether to administer a new drug.

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For the record, the way I answered the question posed at the end of Act 1 is basically, my prior is that there is no theoretical reason to expect an anti-parasitic to work against viral infections, so if it turns out that it does work, we need a very strong signal from very high-quality studies to overturn that prior, and the signal getting weaker the higher-quality the study is probably a sign that the prior is correct and any residual weirdness is probably something else going on.

In the final analysis, I'd say this was basically correct; even though I missed the blindingly obvious confounder, I was right to expect residual weirdness as opposed to a real, small, inexplicable direct effect. This is generally my bar for statistical explanations: real things tend to come screaming out of the data. Cigarettes cause cancer. Lead is bad for children. Seat belts save lives. If you're squeaking out a tiny effect and trying to disentangle it from a complex web of confounders, you're probably just fooling yourself with stats.

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I say this as an IVM hopeful: this is how you do it. My anxiety about this topic went way down reading this even though I was specifically called out. But I was also given my due. I was not just called named and dismissed (invariably by some person arguing without good faith). Just like with lab leak, the minute I see this discussed rationaly, I can rest easy because I can have faith the truth will prevail in the end. I can live with IVM not being a COVID cure, but I couldn't bear a cure being denied through censorship, supression and the rank propaganda like "horse dewormer".

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I think you misspelt Kyle’s name 😅 Kyle Sheldrick

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I don't like the Alien metaphor. Like you said, some of these people aren't stupid, some even have PhDs or Medical degrees. They know what a vaccine does, and that it can't be used to control people, unlike a microchip which literally has logical circuits built into it.

To me, there are two layers of fear here: one is people who dont like needles. This is a lot more than you think, because admitting you're too afraid of needles makes you essentially a child. The other is that they're afraid of side-effects. But instead of voicing these fears, they've managed to turn them into bravery, claiming they're against the establishment or that they are too tough to worry about covid.

We basically have a society so ruined by individualism that no one can be vulnerable.

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Your second outcomes table (the one resulting in p = 0.04) should probably say "Hospitalization" instead of "Death" in the row for Together. (Also, for others who have been wondering where to find these hospitalization numbers in the given link without watching videos, they are on page 21 of https://dcricollab.dcri.duke.edu/sites/NIHKR/KR/GR-Slides-08-06-21.pdf , inconspicuously linked under "Slides" there.)

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Came across this article Neglected Parasitic Infections and Poverty in the United States, Peter J. Hotez. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154650/ which is interesting in the context of the parasite prevalence conclusion. As it would imply there is more parasite issues in the US than expected, so possibly explain some of the anecdotal reports of invermectin effectiveness? Though would have thought tests would turn up the parasites as well.

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Not buying this. You need to factor in regional prevalence. Trials are run in more sophisticated cities, where prevalence of worms would be far less than the outskirts. I live in Chennai, India, and prevalence of worms would be orders of magnitude away from a randomly picked village in India.

Trials are also run in pretty well funded hospitals, which again naturally have a self-selection for wealthier people who again will be far less likely to have worms.

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Worm factor: If everyone is getting IVM to treat the worms, there are no more worms to kill that could factor into the covid19 infection outcomes. General availability in the bodies of those people taking it could be the real reason there's much less infections and bad outcomes generally. See Nigeria (average age 20, less co-morbidities in general, ...).

It's a red herring.

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Congrats!

Just sharing one piece of evidence that made me decide ivmmeta.com is untrustworthy. After Gideon Meyerowitz-Katz pointed out problems with many of the studies, ivmmeta.com published a response to him (sidebar "Respones", ctrl-F "GMK"). I don't have the time and energy to address the object-level issues in the studies. However, I did a quick search for "We note that this personality [GMK] has an extensive history of incorrect advice, including for example..." and found out that all the examples given were manipulative or outright false (read: pure slander). That was it for me. If they lie or manipulate with something easily checkable (whether X ever said Y), why should I believe them in subtle statistical issues?

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One of the best things I have read. But you leave out risk and reward. The risk for almost all people to take ivermectin is basically zero, the reward for some people (maybe with worms that decrease their immune response) is positive with a high likelyhood.

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Firstly, thanks for writing about Ivermectin. I've had no particular opinion on this from the start, but have a friend who got very into it, and I never had the energy to dive in and try to figure out what's really going on. I feel now that there's no need to, because I can't find anything obviously suspect about anything you've written.

Secondly, I think you are way over-analyzing the vaccine thing. I am not vaccinated and there's very simple reasons why: I don't trust the claims of safety. The reasons are very simple:

1. Most of the people I know who took the (mRNA) vaccines told me the shot made them very sick for a day, sometimes two, sick enough that they couldn't get out of bed. One time a bunch of us met up in a bar, and one friend didn't turn up. Another said that she was getting her shot today and everyone just sort of nodded, right, that explains it. Of course you can't go party on the day you get your shot.

This is not the definition of "safe", this is what the word "toxic" means. As far as I can tell nobody tracks these events or cares, people are being told to expect them and there zero credible investigations of these sorts of events.

2. Through my girlfriend, I know a group of women in the 20s and 30s and many of them now have messed up periods. For one, her period has vanished entirely for months. For others it's changed, and one now bleeds almost all the time.

None of them have formally reported this, doctors are basically telling them to go away ("maybe it'll get better") and this is true even in the case where the doctor herself said she had exactly the same problem. Menstrual problems are one of the top class of AEs reported to VAERs get as far as the system is concerned, they don't happen and the vaccines are totally safe.

I will shout this to make it 150% clear - I CAN SEE PEOPLE AROUND ME GETTING INJURED. I can also see that this does NOT surface in any official or formal scientific capacity and the databases of adverse events are being totally ignored; papers that try to use them tend to get retracted for bullshit reasons like "you aren't allowed to assume causation in this dataset", even though assuming causation is the only reason those datasets are collected in the first place.

My problem isn't that I perceive scientists as mystical advanced aliens with unknowable motivations. I understand the science behind this stuff just fine and have done paper reviews myself before. My problem is that I perceive them, alongside journalists and public health officials, as having succumbed to a quasi-cult like mindset in which absolutely nothing may be allowed to slow down the vaccine rollout. Because tradeoffs are hard, they just refuse to admit they're making one at all by claiming there basically aren't any safety concerns. And then when people look around them and think, "um then why does it make people sick" they just get forced to take it anyway.

You don't have to be some anti-science rube to realize that what's going on here isn't science. Science means collecting data and asking questions. I see no data being collected and anyone who asks questions is immediately purged.

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If only there was an much scrutiny on the studies supporting mask mandates and vaccine efficacy.

Masks: talk about statistically insignificant results and very few large scale RCTs.

Vaccine efficacy: Regulatory capture and lack of oversight: https://www.bmj.com/content/375/bmj.n2635

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I love how 34lbs of meth was seized, and 33.5lbs made it all the way to evidence lol

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Well, while I'm patting myself on the back, let me repost a comment of mine from the September post "Too Good To Check: A Play In Three Acts" where I was trawling through the Cochrane meta-study:

Deiseach Sep 7

(6) India (different study):

DISCUSSION: In this study we did not observe any benefit of adding ivermectin to the hydroxychloroquine in the management of patients of SARS-CoV-2 resistant to standard care treatment. Our finding are based on small cohort of asymptomatic or patients with mild symptoms of COVID-19.Such patients were recruited when they did not responded to the standard treatment. Ivermectin was tested as an adjuvant drug to the standard treatment with hydroxychloroquine. On comparisons of patients receiving hydroxychloroquine plus ivermectin with the patients receiving hydroxychloroquine alone, no significant difference was observed in the cure rates. There were no significant adverse effects were observed in patients receiving ivermectin. The use of ivermectin 12 mg single dose as an adjuvant to standard treatment was based on the widespread uncontrolled studies that suggested that the ivermectin has antiviral activity against a broad range of viruses. .Based on these studies it was concluded that ivermectin's nuclear transport inhibitory activity may be effective against SARS-CoV-2.

(This is one of those "throw it against the wall and see what sticks" studies; ivermectin didn't do much but that's not what they were studying. Result here neutral again, I think).

(7) Argentina:

Findings: The trial run between May 18 and September 29, 2020 with 45 randomized patients (30 in the IVM group and 15 controls). There was no difference in viral load reduction between groups but a significant difference in reduction was found in patients with higher median plasma IVM levels (72% IQR 59 – 77) versus untreated controls (42% IQR 31 – 73) (p=0·004). The mean ivermectin plasma concentration levels also showed a positive correlation with viral decay rate (r:0·47, p=0·02). Adverse events were reported in 5 (33%) patients in the controls and 13 (43%) in the IVM treated group, without a relationship between IVM plasma levels and adverse events.

Interpretation: A concentration dependent antiviral activity of oral high dose IVM was identified in this pilot trial at a dosing regimen that was well tolerated. Large trials with clinical endpoints are necessary to determine the clinical utility of IVM in COVID-19.

(This one contradicts the Bangladesh and Spain studies about reductions in viral load, but it does show 'something something need high doses').

(8) Colombia:

Findings: In this randomized clinical trial that included 476 patients, the duration of symptoms was not significantly different for patients who received a 5-day course of ivermectin compared with placebo (median time to resolution of symptoms, 10 vs 12 days; hazard ratio for resolution of symptoms, 1.07).

Meaning: The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand effects on other clinically relevant outcomes.

(And this one contradicts the Indian 5-day trial. They don't seem to have seen a positive effect re: mortality, and they did manage to screw up the 'which group gets what' dosing. Read the whole thing: https://jamanetwork.com/journals/jama/fullarticle/2777389)

(9) India (different study):

In our study subjects, Ivermectin did not improve the time to symptom recovery, clinical status at day 14, or hospital-free days at day 28 after drug administration. Similar results were observed in the only other randomized-trial of Ivermectin (12 µg/kg) in predominantly mild COVID-19 patients (n=62) in Bangladesh, wherein Podder et al(19) found that Ivermectin failed to hasten the resolution of symptoms compared to usual care. The same investigators repeated RT-PCR only once on day 10 and found that most patients had attained a negative result(19). In contrast, we performed RT-PCR at days 3, 5 and 7 to serially evaluate decline in viral load with Ivermectin. Our rationale was that faster viral load decline may enable the non-severe COVID-19 patient to become non-infectious sooner, thereby limiting the contagion. Indeed, it has been shown that at a lower viral load (CT > 24), infectivity declines with lower viral culture positivity(20). Hence the trend towards increased viral negativity at day 5 with ivermectin 24 mg in our trial, particularly among mildly ill patients, encourages further exploration in this regard.

In a retrospective study of hospitalized patients in Florida(21), patients who received Ivermectin were found to have a significantly lower mortality that those who did not (15% versus 25%). The mortality benefit remained significant after propensity-matched analysis and adjusting for confounders. However, they included patients with greater illness severity than our study population, illustrated by lack of mortality in our trial. Furthermore, the greater use of concurrent therapies and retrospective design preclude drawing definitive conclusions from their data. Nonetheless, we did find a 56.2-61.5% RT-PCR negativity among moderately ill patients who received Ivermectin at day 5 of enrolment. The immunomodulatory rather than antiviral effect of Ivermectin may be hypothetically more important in moderate and severe COVID-19

(Interesting results that you get more bang for your buck, as it were, if you take your ivermectin after a meal and with booze. Again, some contradictory findings).

I'm not going to go through the whole list, but going by this, if you want ivermectin to work, then you should be in India (parts thereof), Bangladesh, or Florida.

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The social takeaway is an alluring story, but it's a little pat.

I, too, am a temporarily-embarrassed expert of all kinds. Also, about half the people I know are creationists, but a surprising number of them are conversant with science and expertise - both the immunologist kind where experts wear white lab coats, and the plumber kind where experts keep the immunologists from sloshing through poop on the walk to the metro.

My personal feeling, and that of all the thoughtful vaccine-hesitant and ivermectin-curious people I've talked to about it (n~=10) is that I'm very angry at the authority-experts, I feel manipulated and spoken down to and frankly betrayed. If anyone is treating anyone like a horse, it's the elites who want to herd me into the corral. I couldn't care less if it's for my own good, or even if they're right about it - I resent being treated like cattle. The risk I perceive from a little vaccine hesitancy (I got the shot when it became convenient, but no sooner, and I don't even remember which one) and a little ivermectin curiosity (I've never even seen ivermectin but I wouldn't turn it down if someone passed me some at a party) is very low, and it trolls the Confident Ones so it seems like a pretty safe way to vent my anger and resentment at them.

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"I know that even if somebody wanted to control you by sneaking a microchip into a vaccine, that’s impossible with current technology. I know enough about politics and economics to know it’s really unlikely that some cabal of elites has developed super-futuristic technology in secret."

Well, and there's shady shit like this to make people go "See? SEE??? You can't trust the bastards!"

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60900-4/fulltext

"On May 2, 2011, President Barack Obama announced that the US Central Intelligence Agency (CIA) had located and killed Osama Bin Laden. The agency organised a fake hepatitis vaccination campaign in Abottabad, Pakistan, in a bid to obtain DNA from the children of Bin Laden, to confirm the presence of the family in a compound and sanction the rollout of a risky and extensive operation. Release of this information has had a disastrous effect on worldwide eradication of infectious diseases, especially polio.

On May 16, 2014, the White House announced that the CIA will no longer use vaccination programmes as a cover for espionage. The news comes in the wake of a series of militant attacks on polio vaccination workers in Pakistan, with legitimate health-care workers targeted as being US spies. The attacks have forced organisations such as the UN to suspend polio vaccination efforts in Pakistan, and have severely hampered anti-polio efforts, with parents refusing to have their children vaccinated. News of the vaccination programme led to a banning of vaccination in areas controlled by the Pakistan Taliban, and added to existing scepticism surrounding the sincerity of public health efforts by the international health community.

Consequently, WHO declared that polio has re-emerged as a public health emergency in Pakistan—one of only three countries, including Afghanistan and Nigeria, where the disease remains endemic. According to the Global Polio Eradication Initiative, 61 of 77 cases of polio reported this year have been in Pakistan, and cases of paralytic polio have spiked, with 66 cases reported up to now, compared with only 14 last year.

The lesson learned from the experience in Pakistan is that public health programmes should be politically neutral. Although the announcement from the White House might go some way to building bridges towards that neutrality, health officials and local leaders now have the challenge of convincing communities that vaccination is not merely beneficial, but vital for children."

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I think your framing of the central issue as one of outreach/messaging is mistaken.

Until and unless the central institutions become worthy of trust, many proles will continue to defy them and believe weird stuff instead.

The strategy is not for the Establishment to become better at PR campaigns. It's for it to stop acting like hostile aliens, who (inadvertently, hubristically) created this virus in a lab and then used it as a pretext for a global social engineering effort aimed directly at the lives of normal people.

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Great post.

> I want a world where “I did a study, but I can’t show you the data” should be taken as seriously as “I determined P = NP, but I can’t show you the proof.”

I am not a theoretical computer scientist, but I guess that you could possibly convince me that you had a polynomial algorithm to solve NP-hard problems just by solving challenges of a suitable size -- much like solving sample cubic equations was meant to convince others you had a formula to solve them back in the time of Tartaglia. (This of course will not help if you have an existence proof only or can solve SAT in O(n^200).)

Also, it seems like most people faking data (that we know about) are much less science literate than the people checking them. Carlisle-Stouffer-Fisher and GRIM detection could both be avoided when the fakers would go to the trouble of actually simulating a study instead of just making up percentages on the spot, I guess?

Of course, if you have to publish your raw data, this becomes a lot harder, as people could sanity check any correlations in your sample, e.g. between obesity and smoking. The best way to fake data then might be to take past real patient data, randomly assign them to intervention and control group and discard 30% of death in the intervention group.

To detect this, you would basically have to deanonymize patient data so that people could check the actual outcomes, I guess? Which basically would mean employing a trusted intermediary somehow?

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I think I get where you're coming from with the hostile alien analogy, but the problem is that I immediately put myself in the place of the hostile aliens and started thinking of how I'd have to act to convince the idiot humans to take their brain implants. I don't think your point, though, was that we should imagine anti-vaxxers as members of a less-technologically advanced species that couldn't understand vaccine science *even in principle* and therefore had to be coddled somehow to coax them into doing what we paternalistically knew was best for them.

Rather, I *think* your point was that we should try to imagine what it would be like to have someone who a) didn't have your best interests at heart and b) was totally convinced of their own superiority and c) spoke in some kind of vague or obscuritan manner and made arguments that they seemed to be convinced by but that didn't seem to make sense or seemed to satisfy some alien set of epistemological standards that I had never agreed to.

And for that, I don't imagine hostile aliens. I imagine Orthodox priests. Orthodox priests have told us that it's not possible to get covid - or any other disease - by sharing a communion spoon because (if I understand the argument) something about the transubstantiation process (that is, when the wine becomes the blood of Christ) purifies the wine of all disease. They visit covid wards in hospitals and burn incense and splash holy water onto the covid patients. They say vaccines are a personal choice but what will really protect us from covid is prayer. During Georgia's first wave, when we had one of the lowest covid rates in the world, they told us it was because God had chosen Georgia for protection because Georgian Orthodoxy was the one true religion, and then during the consecutive four waves, three of which were among the world's most severe ever, they were conspicuously silent on the theological implications of that fact.

If the Orthodox Priests announced a special purifying ritual that could cure covid and demanded that everyone go do the ritual, I would not go. Even though the Orthodox Church is the most trusted institution in Georgian society by far and the Patriarch is the most trusted individual by far. Even though most of my neighbors and in-laws would go. Even though people would take the fact that I was not going as a sign of recklessness and some would cry and pray for my poor children who would be exposed to covid solely because of my refusal to go and do a simple, painless ritual with no side effects conducted by the best and most trustworthy people in society, I would not go. Even though I know that "special Orthodox ritual" is 100% safe - safer than a vaccine, even - I would not go.

I know the "science=religion" comparison is stupid and tired and was never a good analogy, BUT lots of detractors of the "hostile alien" establishment view us as promoting our own version of a religion, with Fauci as our Patriarch and, I don't know, Karl Marx as our Jesus. And the problem is there's literally nothing anyone could do that could make me believe that the Georgian Orthodox Church could cure covid with a ritual, and if someone brought me very convincing evidence I would sooner believe that I was mistaken in my interpretation of the evidence than in my belief that religion can't cure sickness with miracles.

So unless the government passed a law that I couldn't work or go to the movies or whatever without my Miracle Ritual Certificate, I wouldn't get one. If they did pass such a law my first impulse would be to see if I could just buy the certificate without doing the ritual. But assuming good enough fraud-proofing I'd just do the stupid ritual and get on with my life. So there's my argument for vaccine mandates. But of course I'd oppose - and vote against - Miracle Ritual mandates!

Just for me, I think this is a better fit for what the inside view looks like for an anti-vaxxer: Vaccine proponents aren't technologically advanced, superior aliens - they're weird priests with funny clothes and meaningless rituals and bad epistemology who very obviously just want to subjugate us for the purpose of money, power, and prestige, who respond famously poorly when their authority is challenged, and who hold inexplicable and damaging influence over society mainly though corruption and indoctrination, and who might at any time decide to try to force us all to participate in their rituals.

The way anti-vaxxers act towards vaccines is more or less exactly the way I act towards Christian rituals, and the way they react to discussion of mandates is more or less exactly the way I react to discussion of things like blasphemy laws.

Then I guess the question becomes: how much does the "inside view" matter, and how much does reality matter? How confident should I be that I'm right that vaccines do work, and Christian Miracle Rituals don't work? How does one move society towards the correct opinion in each case? That seems to be an unsolved problem.

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"I’m not an immunologist. I don’t have the specific expertise it would take to evaluate whether vaccines work."

...

"Again, ivermectin optimism isn’t exactly like vaccine denialism - it’s a less open-and-shut question, you can still make a plausible argument for it."

So, how can you lack expertise to evaluate, yet be sure enough about it to use langauge like "open-and-shut" and no "plausible" argument?

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Lopez-Medina et al is cited often because it shows that ivermectin is only moderately useful. They did it by shortening the observation period to 21 days so they haven't had to observe too many deaths. Even then they had one death in the placebo group and none in the treatment group, but they ignored that completely in their conclusions.

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I would like to see a discussion on possible microbiological ways Ivermectin could work. It's protease inhibitor. The new drug currently being developed by Pfizer with allegedly 90% efficiency is also a protease inhibitor. I am not a microbiologist, but how different could these two be?

Besides that, we should be free to choose what medicine we take, given side effects are clearly explained, no matter how flimsy the evidence for effectiveness is.

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This article really stands out. Thank you very much!

As to the political part: I wonder if the strong US divide between "blue tribe" and "red tribe" doesn't lead to oversimplification, and veiling a diversity of motivations. Lots of anti-vaxxers in western European countries with a strong vaccine-critical movement (at least France and Germany, perhaps Italy too but I'm far less knowledgeable about it) would imho definitely be "blue tribe" if transposed into the American context, and I don't think the medical establishment feels like aliens to them.

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For what it's worth, my guess at the end of part 1 was "if all the small studies show a weak positive effect," and all the large studies show no effect, there's probably a confounder in the small studies that we haven't thought of." Maybe big trials have more people watching and do a better job of randomizing in some subtle way. Maybe Big Dewormer isn't very wealthy and can only fund the small studies. Maybe the small studies are from smaller countries and there's some subtle bias introduced by that.

But I didn't expect it to be worms.

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> People are going to fight hard against this, partly because it’s annoying and partly because of (imho exaggerated) patient privacy related concerns.

I think there are more selfish motives. Keeping the data private means they could potentially slice the data another way to get another publication out of it. Making the data public means someone else could easily scoop them. Requiring pre-registration maybe eliminates this incentive.

Good review overall. I had seen enough to be convinced there was *something* going on with ivermectin, but didn't dig deep enough to ferret out exactly what was going on. Combined with how so much of the criticism seemed ridiculously far fetched and partisan raised my suspicion as well, as you described.

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Trust is hard....

https://thereader.mitpress.mit.edu/why-science-cant-fix-politics/

"""

Scientized debates also tend to be biased in terms of who bears the burden of proof. Many large businesses’ lobbies have demanded that any regulation affecting their products should be rooted in “sound science.” On its surface, that demand seems reasonable. Why would anyone not want regulations to be based on the best available scientific knowledge? However, the implication of “sound-science” policy is that no restrictive regulation of an industry can be developed until proof of harm is conclusively demonstrated.

Scientists are often not able to provide firm answers, especially for complex physiological and environmental phenomena — and typically not in the time scales appropriate to policymaking. As a result, calls for “sound science” end up being a delaying tactic that provides an advantage to the industrial firms producing risky products at the potential expense of humans and nonhuman species — who may be needlessly exposed to potentially toxic substances during the decades spent “proving” harm.

Political scientism starkly divides societies into friends and enemies, the enlightened and the ignorant.

""""

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Absolutely fantastic post. There aren't many people out there writing with such a sincere commitment to unbiasedness, charity towards hostile viewpoints, and the courage to tackle controversial topics. Well done.

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The treatment regimen the American group is recommending includes Vitamin D, Vitamin C, Zinc and a Zinc ionophore (drug that facilitates cellular absorption of Zinc). The ionophore can be Ivermectin, Hydroxychloroquine or Quercetin.

I have been baffled up until now why studies are not looking specifically at the combined treatment, just the ionophore, with no regard to whether it was being taken with Zinc or the other drugs. The fact that even Scott seems to have overlooked this is very concerning.

It's the Zinc that inhibits coronavirus replication. That's the whole theory.

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I think you're giving the study investigators far too much credit, and examining their role with too little skepticism.

https://roundingtheearth.substack.com/p/the-meta-analytical-fixers-part-ii

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Terrific post. There is a flip side to the vax deniers/ivermectin promoters. The popular coverage of the ivermectin issue in the MSM was also pretty hysterical. A question: given the apparent low downside risks of taking ivermectin, would it not have been rational to use the drug? In other words, in the absence of evidence that it was harmful to use, given its long track record of non harmful use why not use? Of course, once we have decent reasons to think it does not good then why use it. But as you note, getting to this point was quite a journey.

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> For example, if a paper reports analyzing 10 patients and finding that 27% of them recovered, something has gone wrong.

Great, there's no problem here, but you've used this type of analysis to slam the Nigerian study, and to make snide rhetorical asides about the Nigerian study while discussing other things, and I think it's worth pointing out that the reported data you've highlighted in Babalola et al. is not an example of this problem. It is impossible for 27% of 10 patients to recover. But it's not at all impossible for 50% of 21 patients to recover. That's just a question of how many significant digits you think you should use to report your results.

And as a matter of first principles, as opposed to cultural norms, I don't see a big problem with reporting results that were drawn from 21 people to just one significant digit. There isn't enough data to justify a second digit!

(Am I saying that Babalola et al. were entirely on the level and just nobly setting a higher standard for reporting precision? No. But I'm uncomfortable seeing their study slammed for exhibiting what is ultimately *better practice* than the cultural norm. Call them out for that, and you end up drawing bad lessons.)

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I get why you used a picture of Dune sandworms, but a better choice would have been Flukeman from that second season episode of the X-Files.

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I think you're right that the theory that ivermectin was effective but people in the medical establishment were downplaying, ignoring, or lying about this for financial reason was indeed "extremely plausible," and helps explain why people like Bret Weinstein, who seems like generally a good guy, went so all in on it. With that in mind, I think the political takeaway here needs a couple more points added to it:

1. I don't know how many conferences at five star resorts on Tralfamadore or Coruscant the aliens have attended on the brain implant manufacturer's dime.

2. I don't know the extent of industry capture in the aliens' medical device regulatory agencies.

3. I don't know how much stock these aliens own in the company that manufactures the implant or what kind of swag the company's sales people (sales aliens?) might offer.

4. I don't know to what extent alien medical grant funding decisions are consolidated in a small number of people or agencies, which might be used to create a false image of consensus among the aliens.

5. In short, it's hard for me to develop an accurate picture of what incentives the aliens face, and how those incentives might affect what they say publicly about the desirability of universal brain implants.

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This is sort of off the cuff, but maybe the takeaway should be "Trust decentralized decision making processes, instead of centralized bureaucracies or guilds."

Also, on this point:

"But you also don’t want people to make bad health decisions."

I agree with this on a moral level, but if you don't know which health decisions are bad and which health decisions are good, then don't you sort of need some people to make bad decisions some of the time?

"So what do you do?" Give people as honest and complete a picture as possible and let them choose for themselves what to do with that information. Don't limit people's options unless there are significant externalities.

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I'm not so happy with the "everyone was wrong" conclusion. Everyone wasn't equally wrong. There were people following studies and drawing reasonable conclusions (as you pointed out) and others demonized a harmless medicine that by all appearances seemed to be saving lives. And it actually did so in many places. They might happen to be vindicated (not of their own accord) if we pretend mainstream media only affects the west. Even if you're right, I wonder how many lives were lost in the 3rd world due to the demonization of ivermectin? Is "being wrong" the right expression for this?

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I don't understand why Scott rejects the Ghauri study from Pakistan for non-random allocation of subjects. Wouldn't sicker subjects be given ivermectin, anyway? It seems that the non-random nature of allocation would bias the study towards *not* finding a significant effect for ivermectin, and the study still finds it, supporting the hypothesis that ivermectin has a large positive effect on Covid patients.

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Wow what a great piece of writing (not sarcastic, i promise)

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I think one element of the political takeaway that was understated is the idea of something like normalization of control, and how that plays into commands that are mentally bucketed with other commands.

The idea that the left (in the part of the government sense) loves to have as much control as possible and to overall put in as many restrictions as possible so it's more "in control" isn't a new one; a lot of people on the right hold it. And the idea that the left (in the voter bloc sense) likes being restricted in this way to the point where they will sometimes make obeying restrictions into a performative social signaling type of thing isn't new to them, either.

A lot of these people have accurately noticed that when the government gets "I can tell you to do this" normalized on any particular subject, not only do you never get that particular freedom back but it also makes it easier for the next command to be considered normal. They aren't going to see "take vaccines" as a needle-thin targeted command, because to them it's part of a super-obvious wave of "no, we eventually want to have much greater control over what you can be compelled to do or not do in a lot of parts of your life; do this one so the next one is easier for us, please".

The reason this is distinct is because it deemphasizes the "do vaccines work and do they have microchips" part of things; you can think the vaccines are part of a greater scheme to control you without thinking they have nano-tech control devices, particularly. Imagine the scenario you proposed with the aliens to include "and if they get everyone to have microchips, they've established a precedent where they get greater control over all human healthcare forever" and you are close.

The Last Psychiatrist once did an article on Dove Soap creating arguments on beauty, where the practical upshot of creating the argument for Dove is that they were then viewed as an authority on beauty at least important enough to be in the argument. More simply, they normalized the idea of "If Dove gets something wrong on beauty, that matters" which naturally leads into "Dove matters". Similarly here, the right is correct to notice that if the left can force vaccines on them, then "We are an authority on this vaccine and making you take it" naturally translates into "We are an authority on your health, and can make you do a bunch of stuff".

I actually think part of why "these have microchips to control you" theories got a foothold as easily as they did is because of this; if the political left views this not just as a "get good health outcomes" thing, but also as a "how dare they disobey us; crush the other!" thing as well, then the average person might pick up those "this is also about making sure people know who is boss" vibes and go looking for a plausible way the left gets the control it's clearly seeking from a simple shot. Some people look in the wrong place for the mechanism of control (the tech) but that doesn't mean the actual mechanism of control (establishing an ever widening sphere of places in which one has command) doesn't exist.

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I think the hostility dynamic is waaay more important than the alien dynamic in explaining why some people don't just ignore the medical establishment, but seem to actively go against it. In fact, I think it explains a lot more than people's varying reactions to COVID. Something like 25% of Americans hate something like another 25% of Americans and think latter is out to destroy the former's way of life (and the feeling is mutual). So, yeah, trust is going to be hard to build. And even when the objective evidence is pretty strongly on one side, sometimes people do potentially harmful things just to spite their enemies. In the case of COVID this is even easier to do because the risk is in this weird gray area somewhere between background-level that everyone sort of ignores and existential that scares everyone into the same boat.

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Thanks much for this. Very high value post, and (part of) why I'm glad I support this substack.

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Excellent, really useful. Covers both the scientific and social/political aspects. Really appreciate the effort to pull this together.

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I WONDER what would happen if you applied the same level of rigorousness to the effectiveness studies (and other data, like adverse effect prevalence) available for the emergency authorized vaccines. Not holding my breath tho.

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"So “believe experts”? That would have been better advice in this case. But the experts have beclowned themselves again and again throughout this pandemic"

This whole article could have been summarized in these two sentences, and it's really all you need to know. The establishment has visibly produced a string of completely absurd measures and policies against Covid. Every time you get something like Biden ignoring mask laws, that's a hit to the credibility of vaccines and scientists. It's like OJ Simpson, who got found not guilty because he was guilty, but the police tried to frame him anyway.

I think Scott managed to get this right, but he's softening it by far too much. "People feel like the establishment is hostile aliens" is one thing. "The establishment acts in ways that resemble hostile aliens" is very different. And Scott is putting too much emphasis on the former, and not enough on the latter, and when he does mention the latter, it's things that they're doing at the start of the pandemic, not things they're doing now. Biden ignored the mask laws just a month ago, and eviction bans where Covid is used as an excuse for blatantly political sticking it to the landlords are quite recent. Scott didn't even mention the double standard over BLM riots during a pandemic.

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Well you’ve done it. I think this is in the top 5 list of best things you’ve ever written.

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Criminettlies! Get outside, live. If you have to do such studying, follow the money.

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I was convinced of the conclusion from Deiseach's comment earlier, so no surprises for me personally. (Another +1 to Deiseach from me.)

However, the comprehensive treatment made me notice something else:

The places with a preponderance of parasites tend to be the places where medical trials aren't great. The places without much parasites tend to be the places where medical trials are comparatively excellent. This association is not coincidental.

That is, a high standard of quality for evidence may bias you towards interventions that work in developed countries, and bias you away from interventions that work in developing countries, insofar as there is a difference in outcome between them.

And I think this is a lot more of a generalized phenomenon than that statement may imply, and that a high standard of quality for evidence is itself not an accident; we calibrate to the environment we experience.

(Also, the hostile alien thing is quite general, and I've slowly come to a position I'd describe as rational anti-rationality, away from a position I used to occupy in which I believed it was best to believe whatever the best arguments and evidence suggested was true. Increasingly I believe the relevant currency is not evidence, but trust.)

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founding

I wrote about this in June-July: https://www.notion.so/yevaud/The-Treatment-for-COVID-19-e052c9d829d34bc49eb6a2e1d2ad8e63 - the short summary:

1. Ivermectin clearly isn't as effective as a vaccine.

2. Several of the top studies claiming it was super-effective were obviously fraudulent (and now have been proved fraudulent).

3. Ivermectin is almost certainly more effective than a placebo.

4. Even if Ivermectin is basically only as effective as a placebo, it still is probably effective enough to use as a treatment of last resort.

4A. I originally would have had a joke that some of the patients might have worms; it did not occur to me that patients actually having worms might have been a significant factor in some studies.

5. Many of the studies saying that ivermectin doesn't work aren't actually proving that, they're only proving that it isn't 90%+ effective or that they are bad at determining study size.

6. The Scientific Establishment has failed miserably here. There should be at least one "gold standard" Western trial with at least 2500 people.

6A. Also the political establishment has failed miserably here; why didn't Ron DeSantis and the Florida Legislature order the state medical establishment to conduct a study?

7. Publishers such as Elsevier regularly publish crap; they publish both pro-IVM and anti-IVM crap so it is presumably incompetence.

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Perhaps the worms are killing COVID in the same way COVID may be killing influenza.

https://eugyppius.substack.com/p/the-disappearance-of-influenza

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*standing ovation

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Indeed, this was much more than I wanted to know. Will try to get through it though

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If people pushing Ivermectin wanted to be treated seriously they should not have attacked vaccines, attacked masks, did everything in their power to politicize the results, go to the media before having sound guidance, faked data and fell for every drug under the sun just so they don't have to take a fucking known safe and effective vaccines just to make liberals cry. So, yeah I'm truly losing respect for Scott after the last bunch of libertairian edgy, radical centrist articles. Yes he reaches the right conclusion but after peddling apologia after apologia for horrendously bad actors. PS: yes trust the science is a horrible pointless divisive slogan

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Read Alex Berenson on substack. Do you know what else showed no benefit in mortality? Pfizer's own studies of their own vaccine.

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I want to print this out and put it on my fridge.

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A counterpoint to the worm hypothesis: in all the hospitals I have worked, it is standard of care to give ivermectin to any patients before starting high-dose corticosteroids (to prevent disseminated strongyloidiasis), long before COVID. My experience is only in tertiary hospitals of a single city in Brazil, so maybe it's not a widespread practice and ivermectin might improve outcomes in other places, but at least here, but at least here, the main effect of ivermectin has been gastrointestinal symptoms in patients talking it

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I did a very quick search and there are a few studies out there that suggest that parasitic intestinal worms actually reduce the severity of Covid19disease outcomes. For example https://www.medrxiv.org/content/10.1101/2021.02.02.21250995v1 Perhaps someone with more research experience than me would look into this here since it seems relevant to this hypothesis put forward by Scott?

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All this accomplished was increase my belief that Scott in the pocket of Big Pharma.

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I wrote this a few months ago.

A Covid Mystery -- A Possible Prophylactic

We have a mystery. The US has 30 times the population of Haiti. The US is the richest nation in the world with the preeminent medical establishment. Haiti is one of the poorest nations where medical care depends to a significant degree on the organizational efforts of one man: Dr. Paul Farmer.

Covid-19 deaths per day (7 day average) in the US peaked around 3400 deaths per day. Covid deaths per day in Haiti peaked at 6.

3400 divided by 6 is 567. The ratio should be 30. In fact it should be lower than 30 considering the glaring difference in resources.

There have been 751,815 deaths from Covid in the US but only 658 deaths in Haiti.

https://www.worldometers.info/coronavirus/#countries

1142 times as many deaths in the US!

How do we explain this? We need a list of hypotheses and widespread use of prophylactic ivermectin in Haiti is as good as any other hypothesis I have heard.

A prophylactic treatment is different from a cure. Daily aspirin in small doses has been recommended to reduce thekk likelihood of heart disease. This does not mean that aspirin will cure heart disease.

Ivermectin may not cure Covid and yet be a prophylactic which reduces the chance of getting Covid.

A COVID-19 prophylaxis? Lower incidence associated with prophylactic administration of ivermectin

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698683/

Using the drug ivermectin for prophylactic or preventive purposes among healthcare workers with high exposure to patients with the virus reduces the risk of presenting symptomatic Covid-19 by 74% compared to their peers working under the same conditions.

https://dominicantoday.com/dr/covid-19/2021/09/13/use-of-ivermectin-reduces-risk-of-covid-disease/

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The Strongyloides stercoralis hypothesis is interesting but it seems pretty speculative. The prevalence of infection in these areas that are supposedly "teeming with worms" is in the range of ~10-15%, and most of those infections are going to be light. It's possible that those who are infected are at greater risk of death when hospitalized with covid, and also have that risk attenuated when treated with ivermectin due to the deworming effect, but again that's speculative. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7349647/

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Here's a JAMA paper from July 2020 discussing the issue with steroids and worm infections being treated by ivermectin:

Stauffer et al.

https://jamanetwork.com/journals/jama/fullarticle/2769100

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So I tried to read this on my phone while making the bed. Didn't work out very well. So made my oatmeal, walked the dog, worked the Wednesday XWord, went and picked up some more oat milk and sat down at my computer.

Much easier on a bigger screen. Especially the graphs.

Hmmm... worms. Okay.

So I got here kind of late and am trying to infer the content of the deleted head posts to some of these long threads.

Muy, muy frustrating for some of these.

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Thanks, I am "pro Ivermectin" because I found in silico studies showing attachments to several viral proteins to be fairly compelling, and I greatly appreciate your work of having actually read all of them.

I intrinsically tend to give pro-Ivermectin studies the benefit of doubt because nobody financially benefits from a positive finding. This is of course an implicit bias and also just my opinion.

The sidebar on worms is actually highly intriguing.

My "vaccine distrust" comes from several sources:

--A Vaccine centric theory of beating Covid has a fairly hard time accounting for the fact that Africa is not on fire. Younger population, warmer climate or genetical immunities could contribute, but the counter examples of somewhat similar in these metrics Brazil or India would in part disprove this. As such, the existence of a possible Africa specific Coronavirus-like, or Covid being effectivly treated with "non standard treatments" would seem plausible, and Ivermectin would solve the "Africa riddle" while also having a mechanism of function according to multiple in Silico studies. If one believes in a possible "Covid-Vaccinia equivalent" to "Covid-Variola", then we should certainly send some crack scientists there to figure that out yes?

--There is of course an emotional and psychological factor. I have a major in Theoretical Biophysics. Journalists and "experts" who are cleary not demonstrating "subject mastery" tell me what to do and what is science and restrict my freedoms.

--While I am pro Vaccine, I am skeptical of m-RNA vaccines if a safe conventional vaccine like Sinovac is available and has been used 3 billion times in humans. The issue with m-RNA vaccines is that Covid can at least evade the immune system more easily, on account of m-RNA vaccines only presenting a single protein. Delta is basically 3 point mutations on the spike protein.

Sinovac would be more of a generalist, and perhaps less strong against any individual covid strain but reasonable against all of them.

--A reasonable case can be made for Ivermectin in that it does no harm, and a very reasonable case if you simply see it as a mostly harmless (we know the side effects reasonably well) placebo. Giving it, under controlled conditions, safely to people who want it is imho fine.

Declaring reverse jihad on "Horse dewormer guzzling rednecks" is completely out of line.

Nothing stops you from being vaccinated and taking ivermectin. One is prevention, the other is cure. The vitriol against it is so out of line that my admittdely conspiracy spidey senses are tingling.

--Concerning myocarditis from vaccinations, I am of the opinion that this is due to accidental intravenous rather then intramuscular injection (a phenomenon also known from smallpox vaccine). There are pragmatic ways to reduce the odds of this, and probably save hundreds of lives. That this is not done seriously galls me.

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TLDR, but the most obvious comment, far as I saw he didn't mention the fact that two of the four negative studies were massive overdoses, and no discussion of zinc. it was obvious in spring 2020 that the cabal tried to get out front of early treatments by offering fraudulent studies of both HCQ and Ivermectin, including studies set up to fail by massive overdose of IVM, and studies on patients already on vents or nearly.

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Thank you for doing this.

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>They would feel like immunologists are some sort of dark and terrible figures from a shadow dimension they could never reach. They would seem like aliens.

I like the rest of it but... this doesn't feel like it fits. Too many people I know in research and medicine and immunology still have close family who are anti-vaxers.

Like, sure, don't believe the sinister Other.

But this is people who have close family who can say "Mom, I literally worked in the team that did that research, there's no microchips, the vaccines aren't for targeting jewish space lasers" and yet Mom or Uncle Harry still believe the daily mail and facebook memes over their close family.

It's more like the creepy hostile aliens managed to slip those brain control chips into a chunk of the population and then they all short-circuited leaving them believing a laundry list of things that don't make even a little sense and their friends and family can't get through to them.

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Genuine question. How confident should we be that mRNA technology has no negative long-term effects? For context, I ran out and got three shots of mRNA vaccine as soon as possible.

As I understand it, the mRNA technique is getting a lot more directly involved in the body's chemical pathways than previous vaccines. Is there strong evidence and theory that this can't affect these or other pathways in unintended ways? Do we have strong evidence and theory that the reprogramming of these pathways won't have longer term effects on the immune system's reaction to the body's own markers (e.g. either making it more permissive and allowing cancer or less permissive and creating auto-immune responses) or affect gene expression (even if it doesn't affect DNA) etc.

If you google these questions, you get lots of comforting CDC/FDA pages or very dense immunology papers that seem several steps removed from these questions. But of course, public health communication has consistently been focused on convincing the public to take particular actions, so there's always that nagging question.

Is this a situation where:

1) we just have no idea

2) these problems are ruled out essentially entirely by theory and evidence

3) we think that these problems would have shown up if they were going to, but we can't rule out some edge cases

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Great post. As someone who is 100% convinced Covid vaccines are a Bad Idea, I'd love you to give them the same treatment; my mind is open.

Your alien brain implant metaphor describes my thinking perfectly (yes, it IS a reasonable way to think) — except for two things. I don't distrust science/tists, I distrust the academic establishment, the medical establishment, the political establishment, and the establishment media. It's a question not of malice, but of incentives. I'm sure I don't need to elaborate. Second, the trojan horse Covid vaccines are introducing is not technological or medical (e.g. nanobots, DNA rewriting), it's social. Hardcore imposition of vaccines are a way to suppress independence and redefine "freedom" into a synonym for "security". This is very bad for society, regardless of the science — I just don't see any scientific reason to take the Covid vaccine either (you can mostly thank Alex Berenson for that).

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How about "Trust Iteration"?

I realize this is frustrating for people who want some kind of safety guarantee immediately, or even in a year.

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What I (and many) do not get is why there is not a proper US or EU or whatever PC country/region funded large scale study that actually does a proper job at evaluating Ivermectin. It sounds much cheaper to me than designing a new drug. And this is one of the few aspects that just does not add up.

Another is why it is banned in a lot of countries. If this ban makes sense to you: https://www.youtube.com/watch?v=_gndsUjgPYo then surely your brain works differently (probably much better) than mine.

I think ivermectin believers say that it has to be taken at a very early stage, or before the infection happens for it to be effective. If a PC country wanted to do a study they would need to include this in their parameters.

I do not know whether Ivermectin is useful against COVID but because its side effects are known I would definitely be happy to have some in my medicine cabinet. I have taken a non-PC jab (non mrna, I'd stay away from those), but still if I feel like symptoms are coming I'd definitely try Ivermectin, because what can I lose. Because it is banned, I have no chance to do that.

Whoever used the "my body my choice" slogan to support any political agenda before, if that person is not angry now about the COVID situation (and motorcycle helmets), then that person is two-faced, to say the least.

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@Scott, FYI you can preface a search term in google with "-" to exclude it. E.g., "ahmed bangladesh ivermectin -elgazzar"

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Solid work. Very well done! Congratulations.

A few critiques for your consideration:

1. Given who you are, I'm surprised by the absence of a Bayesian analysis, and more than almost any other factor than tribalism (vide infra), this seems relevant to how people made up their minds in this case:

1a) How often do studies from Argentina or Bangladesh end up violently overturning medical consensus opinion in the US or Europe, meaning amazing things are discovered in Sao Paolo that were totally overlooked in London or Seattle?

1b) How often do vaccines succeed in almost entirely preventing a viral disease (or its evil consequences)? How often do they have strange awful side-effects not detected in the initial approval studies?

1c) How often do repurposed antibiotics, or indeed any small molecule drug, end up being powerful cures for viral disease?

1d) How often are public health policy people dead wrong?

1e) Notwithstanding (1d), how often are public health policy people *initially* wrong (when a problem first appears), and how often are they unrealistically overzealous all the time?

1f) How often in a person's personal experience have they been told something confidently by a soi-disant smart/educated/credentialed person that turned out to be wrong? How likely is it that people in general overestimate (if not outright misrepresent) their own competence in areas not exactly within their training and experience?

1g) How often do politicians in search of votes and pundits in search of page clicks oversimplify or overdramatize if not caricature the stakes in a debate, the importance of the favored outcome, or the villainy/ignorance of the supporters of the disfavored outcome?

2. When you discuss the tribal aspects of this, you seem to assume that members of each tribe arrive at their conclusions completely independently, and ask "What common experience could lead all these people to *independently* arrive at Conclusion X?" But this overlooks the very nature of tribalism (or indeed of social movements, fads, bubbles, et cetera) in that for a large number of members of a tribe, the reason to have Conclusion X is merely because it's a dogma of the tribe.

Consider the thought experiment: if nuclear power plants had been invented by a bunch of bearded hippies funded by Greenpeace in the 2010s as a solution to global warming, instead of by a bunch of pocket-protector-wearing narrow-necktie poindexters in the 1940s funded by the military to build awesome weapons of destruction, would you not see a neck-snappingly abrupt reversal of positions pro- and anti- among a very substantial number of people?

Human beings are perfectly capable of believing, or at least subscribing to belief in, propositions that go strongly *against* their own inclinations, or available evidence, if it promotes their social belonging in the right way. I'm a little sorry you didn't tackle this issue. It's certainly discouraging, in one sense, because it says *no* amount of improved access to information, education, less screwups by the expert class, et cetera -- *no* difference in what is available to the individual thinking it over -- will reduce tribalistic splits on issues, because these do not arise in the first place from distinctions in individual awareness. They arise from the requirement of any faith group to have a dogma, and to insist on faith in the dogma as a condition of membership.

3. Along these lines: your final prescription ("How can we get more people to trust (but verify) the experts I trust (but verify)?") reads a little tribalistic itself. Have you considered the possibility that nothing is actually going wrong here? Science and expert opinion is being severely challenged -- is that a *bad* thing, generally speaking? Maybe not! It's not like your (and my) preferred worldview here ("vaccines work well, you should all take one, you can take/not take ivermectin if you get sick, according to your personal beliefs, but you should be reluctant to become a zealot about that and try to persuade others to do so") isn't dominant. It is. Most people get vaccinated. Most people don't become ivermectin crusaders. A few people fall into the other categories in both cases, and it causes strife and dissension, and the majority is compelled to accommodate this to some extent or other: compromises have to be made in legislation and regulation and decree, room must be made for disagreement that the majority finds futile or stupid.

Is that a *bad* thing? Maybe that's actually how a republic should work. Maybe the fact that a minority that feels strongly about something that the majority finds ridiculous *should* be allowed to carve out a certain amount of space for its beliefs, and should be able to disrupt the ability of the majority to get its way, a bit. Even if it costs lives? Yeah maybe. It's probably more important in the long run that the everyone remains mutually committed to the republic and solving problems by voting and argument (rather than weapons and death) than that every life that can be saved is.

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founding

Regarding "People [researchers] are going to fight hard against [releasing their raw data], partly because it’s annoying and partly because of (imho exaggerated) patient privacy related concerns."

If your belief is that compromising patient privacy doesn't actually harm them as much as one might infer from U.S. cultural/legal norms about this then hey -- you are the psychiatrist, and plus you have lots of personal experience with the harms of loss of privacy, so I won't argue with you about that!

But if your belief is that patient reidentification from a data set is a difficult thing to do, or would be unlikely to happen in the real world, then I am sad to inform you that this is just false.

Difficulty:

As I am sure you will have heard, it takes only 33 bits of entropy to uniquely identify a living human somewhere on this planet. If you know the person is in the USA, you are down to 28 bits. If you know their gender, there goes another one. If you know there state, there goes a couple more. Approximate age, a few more still.

Once information is released, it can never be un-released, but it can be combined with other information.

It can be surprising what has been shown to uniquely identify people. A few links from a social relationship graph -- not the actual names, but just the shape of the graph in your immediate neighborhood[1], your home and work location[2], of course your browser's device fingerprint[3], or your writing or coding style[4].

Likeliness to happen:

As just one example, internet advertisers in the sketchier/less-ethical parts of the adtech universe have large monetary incentives to reidentify users, using whatever data they can get their hands on, and though they are unlikely to make public statements about their efforts, their capability has been repeatedly demonstrated.[5]

Whether privacy harms are outweighed by society's interest in learning true and important facts about the world using the scientific method:

Man, I have no idea. Sorry. :(

[1] https://33bits.wordpress.com/2008/12/15/the-fallacy-of-anonymous-institutions/

[2] https://33bits.wordpress.com/2009/05/13/your-morning-commute-is-unique-on-the-anonymity-of-homework-location-pairs/

[3] https://en.wikipedia.org/wiki/Device_fingerprint

[4] https://freedom-to-tinker.com/2015/01/21/anonymous-programmers-can-be-identified-by-analyzing-coding-style/

[5] https://dl.acm.org/doi/10.1145/3372224.3419205

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I disagree with the sociological takeaway, and probably a few other takeaways as well. You seem to be suggesting that we should have had an answer for whether ivermectin was effective before we had an answer. Why? Because this had become a red/blue tribe issue? Because you couldn't talk about it on social media so we should circle the wagons and say those people were eventually justified? Because we should have a way to decide based on incomplete data, or based on an incomplete understanding of confounding factors? I don't see it that way at all.

The problem, as I see it, was that there was credible evidence that something was going on here, but also serious reason for doubts. Some smart people were saying exactly that, and not challenging individual decision-making based on the available data. They said, "Sure, there may be something there, but it's not clear yet whether it's a good treatment, for whom, or under what treatment circumstances" (early/late, treatment/prophylaxis, genetic profiles, other proposed subgroups). That was a reasonable set of conclusions to come away with from the data available.

Scott's discussion of "how should we have been treating this all along" misses the point. Crafting heuristics that lend more certainty than the data support is just plain bad practice.

More generally, there was the community touting ivermectin as a great replacement for vaccination, and the reactionary community that condemned ivermectin as an evil distraction. Okay, but that's just people whose heuristics led them to greater certainty than the data supported. If there's anything to learn from them, it's that we should be aware how others' bad heuristics - and fighting over bad heuristics - can lead us toward greater certainty than we should have.

The real takeaway should have been something like, "Let's not settle for a simple yes/no answer to this question. Instead, let's call this an open question and look into it more seriously."

This is what we do in less politically charged areas. We keep looking until some intrepid researcher does an interesting subgroup analysis that generates a hypothesis. That hypothesis is tested and (unlike the dozens of other hypotheses we end up rejecting) we discover some confounding factor we hadn't considered before.

In this case, I think you've buried the lead on ivermectin. The lead should be, "Ivermectin may be a lifesaving treatment for COVID-19 sufferers with parasitic worm infections." It looks like that's a promising subgroup explanation of whom this drug works for. This feels like an excellent opportunity to promote de-worming efforts around the globe and save lives. Too bad it got politicized as a binary "cure/hoax" before we could figure out the real answer to the question.

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> am I secretly suggesting that we make rationality higher status?

I'm all for it, but asking society to become rational enough to make a dent in the problem seems infeasible. Between "believe X" and "become significantly more rational", there must be some message/framing that would improve this whole situation.

And I think Scott identified likely the best take:

> we have to make the scientific establishment feel less like an enclave of hostile aliens to half the population... But I don’t really know how to do that, and any speculation would be too political even for a section titled “The Political Takeaway”.

But I'm happy to speculate!

1) We just have to engage with people. The overall conclusion of Lee McIntyre analysis in "How to Talk to a Science Denier" felt viscerally right to me: science deniers can be convinced if they can just talk openly, candidly, *safely* with more rational people. "Safe spaces" are a wonderful idea Our schools, universities and institutions purport to have safe spaces, but they aren't safe for the people that likely need them most: the half of our population that is not liberally aligned.

2) In absence of those healthy, personal relationships, people will turn to whatever authority is most prominent in their lives. And we have horrible, evil, awful people in positions of authority. I don't actually know how, but the required outcome is obvious: get money out of politics, and invest in public media.

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Hi Scott. Really thorough review of the IVM studies that helped confirm what I've been thinking - there's just little data proving effectiveness. The roundworm incidence was an eye-opener, though.

When you mention myocarditis, though, it seems you pooh-pooh it just a little bit. The thing is though is that the incidence in young males has really surprised the CDC and caught it a bit off-guard. The whole of the vaccine safety meetings are available published at

https://www.cdc.gov/vaccines/acip/meetings/live-mtg-2021-08-30.html

And in particular CDC showed how far actual cases of myocarditis exceeded their prior estimates in the slide in the YT video linked below. Their estimates were for single-digit numbers but instead they found real-world incidences in the hundreds.

https://youtu.be/mfFeocgSKvU?t=204

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For your alien analogy to work, wouldn’t most humans have to already have chips implanted in our brains, provided by the same aliens who want us to get this new chip?

And the already-installed chips would be for mimetic plagues we’ve never actually seen break out in earth, much less Jill someone we actually know. Whereas this new mimetic plague is one where we can observe the effects within our own communities.

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Avi Bitterman - one doctor that was cited - has an updated regression. https://twitter.com/AviBittMD/status/1460855430805180421

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Not only is ivermectin boosterism strongly correlated with anti-vaxxism, it also strongly correlates with Trumpyness, FWIW.

Also FWIW, I am neutral on ivermectin; it may be of some benefit and I am willing to see. That said, both pro and anti camps are so polarized, that no amount of research, logic, facts or evidence will convince most partisans of either side. Strongly in favor of vaccines as a general principle. Detest Team R and Team D about equally, most days.

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Really enjoyed this one.

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When I read Scott was going over 30+ studies of Ivermectin - I thought about switching to TikTok. Stayed - and will soon need a new carpet. ROFL. - Funniest piece ever. And more depressing than Moloch. WTF went wrong with "science"?

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It works because ivermectin is a protease inhibitor and keeps the virus from replicating and kills worms.

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score one more for the Maps sans New Zealand : (. I've been thinking a lot about #trustthescience from an epistemology point of view lately, there is definitely something in that. The scientific method was never really designed to generate trust among non-experts, it was designed to generate truth when operating over the smartest and best resourced experts. There is probably a need to develop a new epistemological system from the ground up to try and grow a deep and reasonable trust, a hashtag is not really going to cut it. (Requiring data to be published would be a damn good start though...)

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Probably the best attempt at making a case for vaccines from a "not an alien" point of view that I have seen is this one by conservative Christian apologist Neil Shenvi. He tries to argue in a way that "requires minimal confidence in the government, public health officials, doctors, and scientists." https://shenviapologetics.com/a-minimal-case-for-covid-vaccination/

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For a good comparison, look at vitamins. I take OTC pills for A C D K Fishoil Magnesium Calcium and a few others, just bought off Amazon.

Do I need them? Probably not

Did a doctor recommend them? No

Do doctors recommend them as a treatment for anything? No, or else they'd be locked behind a prescription and cost $40/pill instead of ~$0.30 for my daily regimen.

Does anybody think they are directly harmful to me? Not that I'm aware of.

Should I be taking these? Why not? The cost is absolutely negligible and I think there is a reasonable chance I am deriving some health benefit

My self-medication with these is the exact same sort of not "trusting the science" as people taking OTC Ivermectin prophylactically. I think all of the above answers would be the same for an Ivermectin taker. I don't think my position on taking vitamins is in any way unreasonable and would be unlikely to stop unless somebody made a strong argument that they were actually harmful.

With that in mind it feels like the wrath and ridicule towards Ivermectin must come from the (admittedly often accurate) conflation between Ivermectin and Antivaxxing, and the vitriol used to attack my above position is just ludicrous and takes away any credibility the speaker could have.

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So this talk of a "quantum" "memetic" plague...just silliness, right? OR is there something more there?

Cause I don't know if it's occurred to anybody else but there is clearly a Copenhagen Interpretation issue going on with this pandemic stuff. Talking like an individual person is clearly either sick or not sick. When you got these mathematical models and whatnot, though, a person can have a relatively greater or lesser probability of getting sick or not getting sick based on some or other variables.

You and me, we're walking around, according to the modelling on which the public policy is being based we are all in a superposition of sick and not sick, on a probability distribution, right? But obviously a person is still either sick or they are not sick. The probability distribution is collapsed into one or the other state.

Where do people fall on this issue? It's a complicated one, and not distinct from ethics; I recommend reading the play by Michael Frayne.

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Hi Scott, please get in touch with my via twitter. You're using my old analysis here, which was a back of the envelope calculation. My formal analysis is more rigorous and not susceptible to the critiques some are raising here.

Avi Bitterman

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Really good, but I think one thing is worth mentioning: if you don't want to be seen as hostile, don't force people to do things they don't want to do. The extra benefit from compulsory lockdowns, mask mandates, and mandated vaccination and boosters is small compared to the loss of trust.

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To the author: Did you submit your criticisms to the site? If so what was their response. What was your opinion of ivermectin before anaylizing the studies? Did reading them change your mind about anything? Do you have any conflicts of of interest? Are you at all concerned about the EUA creating a multi billion dollar incentive to suppress alternate treatments like ivermectin? Have you carefully examined what reputable critics of the 'vaccine' are saying? Do you think the risk of ADE has been proven to be minimal? Do you think the growing number of incidents reported on VARES are being properly evaluated? Are acceptable and should play no role in people's decision making? Do you think mandates are a good idea?

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The quantum memetic plague sure is funny, and probably catch some of the deep reasons around vaccine fear....But not the "those aliens are part of a circle I can not even imagine me or any of my friends would ever be part of", this is at most a fringe reason. Many technically-minded people have reticence, some (crackpotish, or among the small scientific red-tribe - it's becoming difficult to distinguish between those) health-related scientist are even among the not-so-warm to vaccine crowd.

I think people could trust a utterly alien circle, provided this circle has no past hostility (and preferably some past helpful behavior) to show, so the political aspect (the advice-givers are actually hostile, at least on other subjects) is more than enough for explanation. Add the fact that Covid is not Ebola (if it was, there would be far less space for discussion and far more for riots around pharmacies holding the rationed vaccine), and that's more than enough.

The political aspect in particular is huge: In an increasingly polarized political climate, 95% of biological professors are democrat! I guess it would be enough even if covid was worse. Maybe not Ebola-like, but significantly worse.

This 95% is completely crazy, and I can guess something about the remaining 5%: They follow Greg Cochran. They have stumbled by accident or interest on parts of biology that is taboo to the blue tribe, and, because of polarization, now tends to reject other parts they would never have rejected 50 years ago.

Most parts of my life are linked to techno-science (work, practical hobbies, learning interests), since as long as I remember. But the evolution of science, at least those last ten years, in its public message form, makes me sad. Not to the point of wholly rejecting it, it's still my main interest in life....But now I zap out mainstream media except for mindless entertainment, and get anything I consider seriously from other sources, like this blog.

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About the alien analogy: there must be something more to it, right? Anti-vax sentiments seem to be a primarily Western, First-World phenomenon, though there are many rural, low-education populations in the rest of the world that probably do not identify with scientists.

Also, this article was a joy to read.

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I *love, love, love* the worm interpretation of the data. Also, Scott, a million thanks for finally doing a deep dive on ivermectin.

If there's one thing to be huffish over, it's the tirade against the vaccine hesitant at the end. I swear that my following negative comments will last no more than 4 sentences, and will then return to adulatory effusiveness, but: Ahem - O Thou Who Art Vaxxed - dost thou know what it is to be threatened with termination from thy job because thou dost not wish to take an experimental drug that hath only been around 1 year? I mean, seriously - some of us are being persecuted because we want to wait 2-3 more years to see what the data is on long-term side effects. This sort of hesitancy about drugs is pretty common and is prima facia reasonable. It's not even political, or not obviously so, since (if I can cite findings from a few studies that may or may not be RCTs and may or may not be fraudulent and may or may not be significant and may or may not have confounders, because really we need Scott to figure that out) the vaccine hesitant tend to be people with PhDs and middle-aged women who vote liberal.

That having been said, it helps to have the ivermectin side of things cleared up. And this is the most brilliant thing I've read since the analysis of trapped priors, or of race and police shootings, or the other cool things that Scott comes out with so often that I can't keep track. It really deworms the horse. I mean, it hits the worm on the head. It cuts the Gordian Worm. And now I have to go re-evaluate my supply of ivermectin.

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Hi I am like a fifth through this article but I’ve skipped down here to say the Cadegiani section is the funniest thing I’ve read in months

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Aren't we interested in a very small tail, the 0.03% of people who do not survive COVID? In ML, we have specific model building techniques, usually called Fraud Detection, to build models that will pull out the signal from this hugely lopsided categorical data. Plus you need A LOT of data.

Furthermore, I think it's plausible to put Ivermectin, or any other drug that works "non-intuitively" into a category that only works for a segment of the total population (e.g. let's say the 20% of people who are strongly deficient in vitamin D at time of infection). In statistical terms, an "interaction effect" which can be tough to capture and easy to confound. Overall this is going to be very difficult to tease out from the noise of SES, geographic happenstance and strain potency.

If we had a medical tricorder from the future, is it possible that would identify 1% of the population as strongly benefiting from administering ivermectin on infection / taking it continuously as prophylactic, where P(survive) could be increased by an order of magnitude?

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