It is good that people are doing studies, but at this point adding one more study isn't really headline news so I'm not sure what the up-voters think this will show. There isn't really a need for more evidence as far as I'm aware.
What is far more interesting and useful is explanations of why there are a bunch of studies showing great COVID outcomes when patients are paired with Ivermectin (eg, https://ivmmeta.com/). The best answer I've heard is the geographic distribution of successful studies lines up with parasite-prone countries, so they are actually an interesting example of the base-rate effect.
A lot of it is just straight-up fraud. Gideon Meyerowitz-Katz has documented this in some detail.
Also, ivnmeta itself is just weird. It can only be characterized as a propaganda site. It's well done, but scientifically invalid. They're far, far better at science communication than, say, the CDC (low bar, I know). We don't know who they are or who funds them, though there are certainly correlations with other, generally right-wing or libertarian, flavored groups. Given the number of times it's posted unironically here, it looks like a large number of people have been taken in by it.
> Also, ivnmeta itself is just weird. It can only be characterized as a propaganda site. It's well done, but scientifically invalid.
Ivnmeta and the network of related sites are some of the weirdest propaganda I've seen.
But what's even stranger is how the visual format seems to short-circuit right past people's usual suspicions on sites like HN. Normally if you posted up site where some unnamed author had crossed out the conclusions of various research studies and inserted his own statistical analysis, everyone here would roll their eyes. There's something about this site that seems to short-circuit past people's usual complaints (small sample size, inclusion of retracted studies, substituting statistical analyses that disagree even with the papers it cites) and make people think there's a conspiracy going on.
2. Has a simple pitch (look at all this evidence! here are links and all the details we can find!).
If you are evidence based you have to admit ivmmeta.com is interesting (it compares extremely well to the usual tripe for ordinary people which typically just reports "studies show..." with no links or sources - or like this article, one study in a sea of conflicting and complicated studies). If only the governments of the world had the resource of Big Ivermectin and could summarise data effectively and present it as one would to an adult. Might even work better than mandates and threats, what do I know.
The counterarguments tend to be vague. When this post says "various research studies" - links. Specifics. Names. This is something ivmmeta has that the post doesn't. And that is why ivmmeta is more persuasive communication.
And as far as I can tell, based on the geographic distributions, ivmmeta probably is reporting on a real effect. That helps the argument that they are just good communicators rather than malicious.
PS - fun anecdote, a close family member of mine was diagnosed with threadworms around the time they got their 3rd vaccine shot. Ironically, assuming Ivermectin works on threadworms, they might have had better chances with COVID if they'd taken Ivermectin at the same time as their shot.
PPS - If there is an ivmmeta equivalent for vaccines people should throw it around more. It is difficult to figure out how effective they actually are given the waning of shots and complexity of cross-country policy comparisons.
they literally strip out the paper's conclusions and substitute their own?
is there a long form write up on what ivnmeta did wrong? I couldn't find any, just comments here and there that, and instead of picking who to trust, it might be better if there is a long form going over what exactly and how they did wrong/incorrectly/deceptively.
I assumed they were just cherry-picking studies, but not faking conclusions.
https://twitter.com/gidmk/status/1422044335076306947 is probably the best source on this. GidMK has made something of a name for himself debunking this stuff, for better or for worse. If you want a source that's not associated with him but still critical, though not as detailed, you can check:
It has been criticized for relying too heavily on GidMK, but in my opinion that's reasonable - he is in fact the expert who has studied this in detail.
> A lot of it is just straight-up fraud. Gideon Meyerowitz-Katz has documented this in some detail.
Alexandros Marinos provides a counterpoint [1]
> Reading the article, I was surprised (but not really) by the central role Gideon Meyerowitz-Katz (henceforth GidMK as is his much shorter Twitter handle) had played in the analysis. The man has a way to apparate wherever a person of influence takes a position on ivermectin. This is at least the third time I’ve observed the same sequence of events.
> ...
> I wanted to avoid focusing on GidMK himself, but the way the analysis comes out, this won’t be possible. I’ll try to keep things as dispassionate as possible without being fake, but I beseech the reader to understand that this isn’t your standard “Ad Hominem” argument. If Scott’s analysis depends on his trust on GidMK, it is paramount that I demonstrate that GidMK’s track record is not one deserving of that trust.
> ...
> I have to also note that GidMK is highly conscious of his feed, and is probably applying some automated means of blocking anyone supporting opposing views to his. Not only has he blocked me on Twitter, he seems to have blocked a double-digit percentage of my followers, many of which were not aware of the block until I asked them to check. My best hypothesis is that anyone “liking” anything I posted opposing his positions would automatically get blocked.
There is more I could excerpt, but probably better to read the whole thing.
This is not a counter-point, this is an ad hominem attack (despite its protestation to the contrary) that doesn’t address any of the serious problems that Meyerowitz-Katz found with those studies. Problems severe enough to force retractions from the relevant journals.
The credibility of Meyerowitz-Katz (and others like him) rests on the quality of his claims and analyses, not on whether he blocks people on Twitter.
Many of the early studies weren’t high quality studies. And as I recall a couple were outright fabricated. It takes time to run randomized prospective studies and those are coming out now.
If we have lots of low quality studies that show Ivermectin works well in populations which probably have high parasite incidence, and not much obvious effect of anything in populations where there aren't many parasites (insert puns here about lawyers and politicians)...
What is the high quality study here to prove?
I don't see why the problem is evidence. AFAIK there seems to just be a shortage of people repeating "the helpful effect is geographically correlated" over and over again. Unless there is evidence of a positive effect that I'm not aware of?
I think the difference is that in places where ivermectin had efficacy (India, Sub Saharan Africa, South America), parasitic infection was a significant comorbidity. In much of the developed world, the most significant comorbidities are things like obesity and age (with all of its associated pulmonary and respiratory risks).
So in laymans terms, enough people had untreated and undiagnosed parasitic infections that "they got better" was curing an undiagnosed comorbidity to a positive C19 and since the parasite causes high risk problems eg with kidneys or pulmonary risk or breathing, it helped them survive.
I'd also say covid case/severity reporting is probably of questionable quality in those regions as well, as they struggle economically and probably don't have resources to do that well.
If we look at the secondary endpoints note that 3x as many died in the control group, 2.5x as many needed mechanical ventilation and one third more need to go to the ICU.
Ivermectin Control
n 247 249
Mech vent 4 10
ICU 6 8
Died 3 10
These may not have been primary endpoints and may not have been statistically significant but it does raise the question of whether they would have been significant had a larger sample size been used.
Once you start dealing with small numbers (e.g. 2% versus 3%) then you would need far, far more patients to reach statistical significance.
It's tempting to look at things like 8 people visiting the ICU in one group but only 6 people in the other group and see that 6 < 8, but the problem is that it's too small of a sample size to decide if it's significant. The article covers that:
> There were no significant differences between ivermectin and control groups for all the prespecified secondary outcomes
The only one that almost comes close is death rate:
> The 28-day in-hospital mortality rate was similar for the ivermectin and control groups (3 [1.2%] vs 10 [4.0%]; RR, 0.31; 95% CI, 0.09 to 1.11; P = .09)
If this was the only Ivermectin study out there, it would be worth following up on. But it's not, and when this is added to the rest of the (not-retracted) studies it doesn't really change the picture.
At this point it matters less and less anyway. Countries that already tried Ivermectin at scale are starting to abandon the approach. Legitimately effective COVID drugs like Paxlovid with highly significant differences are becoming readily available. It's time to stop grasping at straws and accept that it doesn't work.
You are right that the study simply isn't powered to detect a decrease in mortality, even if it is there! That said, if true, a 70% reduction in mortality would still be of significant benefit.
You are right that this study doesn't change the picture. It is is just another underpowered study showing a large but statistically insignificant reduction in mortality. Yes, Paxlovid is almost certainly better.
That said, I would like to understand the efficacy of ivermectin with an appropriately powered and designed study. I hope ACTIV-6 reports out this year and used a reasonable treatment dose and timing comparable to Paxlovid.
Not being statistically significant is not a proof that it doesn't work -- it only means they could not reject the possibility that the results were due to chance. The possibility that it slashed the death rate by 3x (which is what happened in the study) when projected to the world wide deaths of ~ 4.5 million would imply saving the lives of 3 million people so it certainly would be worthwhile to check it out. Maybe it was due to chance but maybe it was not.
> The possibility that it slashed the death rate by 3x (which is what happened in the study) when projected to the world wide deaths of ~ 4.5 million would imply saving the lives of 3 million people so it certainly would be worthwhile to check it out. Maybe it was due to chance but maybe it was not.
When you talk about 3x, you're talking about 10 vs. 3. Extrapolating that out to millions of people is not a great idea.
Let's say you run an ice cream company. You round up 490 friends and ask them to pick their favorite flavor of ice cream: chocolate or vanilla. 477 say they don't eat ice cream, 10 pick chocolate and 3 pick vanilla. You rework your ice cream production to be 3x chocolate : 1x vanilla based on your survey and promptly go out of business.
That's what's going on here as well, there's just not enough statistical significance between the two outcomes to infer any reduction in severe COVID cases.
> Findings: In this open-label randomized clinical trial of high-risk patients with COVID-19 in Malaysia, a 5-day course of oral ivermectin administered during the first week of illness did not reduce the risk of developing severe disease compared with standard of care alone.
Also they say they used the Fisher exact test and got a p value for mortality of 0.09 so it seems they were doing a two-sided test which is the default for fisher.test in R.
ivm <- c(3, 247-3)
con <- c(10, 249-10)
m <- rbind(ivm, con)
fisher.test(m)$p.value
## [1] 0.08809225
However, I think a one sided test could be justified and in that case it is significant at the 5% level.
fisher.test(m, alternative = "less")$p.value
## ivm
## 0.04541928
Furthermore a test just twice as large would be sufficient to determine significance at the 1% level even with a two sided test if the same death rate continued to hold.
ivm <- c(3, 247-3)
con <- c(10, 249-10)
m <- rbind(ivm, con)
fisher.test(2*m)$p.value # 2* so that it is twice as large
## [1] 0.008490957
So on the one hand I completely agree with you on the necessity of having enough people to dodge the problem of random chance. "the law of large numbers" on Wikipedia is good.
On the other hand you have three different categories where the numbers from one group are smaller than the numbers from the other group. Could it all be random chance? Sure! But that does kind of hint that there might be something there.
> But that does kind of hint that there might be something there.
The paper does not draw this conclusion. The data you're referencing is too small to be statistically significant.
> Findings: In this open-label randomized clinical trial of high-risk patients with COVID-19 in Malaysia, a 5-day course of oral ivermectin administered during the first week of illness did not reduce the risk of developing severe disease compared with standard of care alone.
> Meaning: The study findings do not support the use of ivermectin for patients with COVID-19.
> Results: Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups.
> Conclusions and Relevance: In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19.
On the one hand, you've made a rebuttal, quoting the paper. That's good.
On the other hand, you've utterly failed to understand what I'm attempting to say. So that's less good.
> The data you're referencing is too small to be statistically significant.
I explicitly acknowledge this.
>> So on the one hand I completely agree with you on the necessity of having enough people to dodge the problem of random chance. "the law of large numbers" on Wikipedia is good.
That's the acknowledgement.
>> But that does kind of hint that there might be something there.
And here's where I'm saying "if you have these three metrics which are independently all non-significant but they're all trending in the same direction, there might be a 'there' there"
Maybe I didn't say it clearly enough to begin with. I'm not alleging that Ivermectin is COVID Jesus and we all just gotta believe in him in order to be saved. I'm just trying to point out that the data previously quoted should probably get a person's "huh, what's that about?" sense going.
> Could it all be random chance? Sure! But that does kind of hint that there might be something there.
Right, which is why we have studies like this: Early studies showed similar "maybe there's something here" type results, which prompted more studies, which later showed that most likely there wasn't something there.
People also seem to have forgotten that all of the other COVID drug research has progressed significantly in the past two years. Drugs like Paxlovid have indisputably significant effects that leave no room for "maybes" like this and should be ramping up quickly. Even if we were to eventually run a study big enough to find some significant effects of Ivermectin, however small, it's already been left behind by other treatment advances.
For some reason Ivermectin sticks as a political talking point, though, so it continues to be debated to death while everyone in the medical research world has long since moved on to better things.
> which prompted more studies, which later showed that most likely there wasn't something there
Do you have a reference to such a study? I was not aware of any well controlled and appropriately sized studies showing a negative result, but I would be open to reading one.
The study says they were given treatment "within 7 days" of onset. The proponents of IVM have always said "early treatment" was required for it to work.
Serious question: Does "within 7 days" meet the definition of "early treatment"? My guess would be "no", but curious what others think.
NOTE: To be clear, I have no opinion here. Just like discussion and curious on thoughts.
In the vast majority of the anecdotes I know where the person developed serious symptoms, they first had quite mild symptoms for about a week or two, sometimes longer. Given how many people develop no serious symptoms at all, I think "within 7 days" is ambiguously but defensibly in the "early" category.
>In the vast majority of the anecdotes I know where the person developed serious symptoms, they first had quite mild symptoms for about a week or two, sometimes longer.
Serious symptoms arent usually caused by the virus, which peaks 3-5 days after symtoms, then dies out.
If you want to treat in the viral stage, early action is incredibly important. If you want to treat the after effects, it is less critical.
It is still a relevant point given recently approved medications like Paxlovid ran their trials with a even tighter window of <5 days and 50% of the trail was <3 days.
They're not using it. Those are Ivermectin conspiracy talking points that are spreading around the internet, but they're either not true or heavily distorted.
I'm still stunned by how these rumors continue to circulate as facts despite being so easily disproven. On the other hand, some of the top Google results I found while looking those up quickly were obvious conspiracy websites with false information. I suppose the misinformation is just flooding the internet so fast that the truth is getting diluted away.
Okay, I'm going to clear up a bit because "they're not using it" is basically a conspiracy theory itself. I think your response doesn't address the question, contradicts itself, and is poorly communicated because of the use of emotional/political buzzwords.
- On August 13th, 2021 The chairman of the Tokyo Medical Association approved the use of ivermectin for covid if a patient gives informed consent and asks to use it. See: https://www.tokyo-np.co.jp/article/123988
So, at least the Tokyo Medical Association in Japan has approved the use of it. Does that mean it's a standard treatment for covid? No, but it does mean that some tens of thousands of doctors in Japan are making it available.
- India stopped using it. That's accurate, and I had no idea this happened because I wasn't following it too closely, but the insinuation is: Well, they clearly were using it. How does that gel with "those are Ivermectin conspiracy talking points" and "I'm still stunned by how these rumors continue to circulate as facts"?
- Brazil, as you concede, is still using ivermectin to treat covid. I agree it's a mixed vibe over there. But again, how does this gel with "they're not using it", "those are Ivermectin conspiracy talking points", and "I'm still stunned by how these rumors continue to circulate as facts"?
So, can you answer the actual question? I'm not interested in what you think is a conspiracy theory. And well shit, I guess I answered the question myself with that last article I linked; it looks like it's a hedge or hopeful shot in the dark. Imagine all the problems we could avoid if you could just say that?
"Kowa (Nagoya City) announced today that it has confirmed that the parasitic drug "Ivermectin" is effective as a treatment for the mutant "Omicron type" of the novel coronavirus. Based on the non-clinical trial with Kitasato University, it was said that it had an antiviral effect."
If you dig into that story, it's just a lab result that IVM shows antiviral activity against Omicron. It does not support your implied claim that Japan is actually using IVM.
I've read that ivermectin is fantastic for treating parasite infections. And that these infections co-occuring with covid can make it much harder for your body to deal with covid. And thus in places where parasitic infections are common it can be a very effective treatment. But in places where they are not it doesn't seem to make any difference.
I suppose that the anti-parasitic effect could explain why doctors in South America and Africa are so adamant about it "working".
But the main idea behind ivermectin being used for covid is actually that it's a protease inhibitor. It essentially could directly prevent the virus from replicating.
They found a bunch of repurposable drugs which have that mechanism earlier on in the pandemic, and ivermectin was found to be extremely promising. Researchers just didn't know under what conditions and dosage it would be effective, since during the tests they blasted all of the drugs at maximum potency.
Since then, well... I have no idea. It seems like ivermectin would have to be given in very large doses to actually work, or modified to fix that issue. But instead everyone seems to just be trying to test/use the normal anti-parasitic doses, and I haven't seen anyone trying to modify it to bring out the protease inhibitor effect.
I think the cases in which it works are probably mostly in people with parasites, but there could be some other circumstance that makes it work sporadically - who knows.
Does any study ever suggest that a $0.10 drug with expired patents is better than the new and patented $30 alternative? If so which benevolent pharmaceutical company funds such studies?
Between doctors prescribing specific medicine "brands" when generic alternatives are available, insurance companies denying perfectly valid claims and forcing you to challenge their decisions in tribunals and similar venues, and pharmaceutical companies engaging in questionable behavior,[1] I am very reluctant to trust anything championed by this unholy nexus.
[1] There is a multivitamin product from Bayer called Supradyn that I have been using for years. Last year, the company changed the formulation and halved the doses of most of the ingredients while increasing the price by 50% resulting in an effective price increase of 300%.
Not all investigations like this are funded by drug companies.
For example, and as a perfectly balanced counterpoint to the one you are trying to make about ivermectin, dexamethasone was rapidly identified as a cheap, easily available, out of patent medication that significantly reduces morbidity and mortality in covid hospitalised patients early in the pandemic by NHS doctors
Better than an alternative? Probably not. Worth using at all? Sure, if the data supports that conclusion. In particular, a lot of labs have been trying a wide variety of drugs to see if any have efficacy against covid. Ivermectin... just doesn't.
Here are three meta-analyses indicating that an SSRI with an expired patent (fluvoxamine) is potentially effective at reducing hospitalization rates for covid:
If it worked, they'd study it to find out what the interaction was or if it was a metabolite that carried the action. Then they'd develop a targetted version of that drug, patent it, and cash in.
It doesn't work. So they haven't.
A good example is major clinical depression and ketamine.
> Does any study ever suggest that a $0.10 drug with expired patents is better than the new and patented $30 alternative? If so which benevolent pharmaceutical company funds such studies?
I hear this a lot to explain the lack of studies. What about this one here though? Isn't this finally a conclusive study debunking all the claims saying Ivermectin alone is a good prevention/treatment for COVID-19?
> Isn't this finally a conclusive study debunking all the claims saying Ivermectin alone is a good prevention/treatment for COVID-19?
No, because they didn't <administer some particular dosage>/<administer it at the right times>/<administer it when the moon was in the right phase/when Mercury was in retrograde>.
A true believer can always keep shifting the goalposts.
>Isn't this finally a conclusive study debunking all the claims saying Ivermectin alone is a good prevention/treatment for COVID-19?
It wont do a good job of that because the study reported 70% fewer deaths for the Ivermectin treated patients than control (3 vs 10), as well as reductions in ICU and ventilator with treatment.
What is far more interesting and useful is explanations of why there are a bunch of studies showing great COVID outcomes when patients are paired with Ivermectin (eg, https://ivmmeta.com/). The best answer I've heard is the geographic distribution of successful studies lines up with parasite-prone countries, so they are actually an interesting example of the base-rate effect.