Without randomized trials you cannot recommend a drug because you cannot exclude confounders. It seems wrong to me to even speak of "overwhelming evidence" without a randomized trial or other sound ways to control or identify for confounders (e.g. causal models).
I’ve included every double-blind randomized placebo-controlled trial I could find of ivermectin as a treatment for covid. Using only double-blind placebo-controlled trials means that only the highest quality studies are included in this meta-analysis, which minimizes the risk of biases messing up the results as far as possible. In order to be included, a study also had to provide mortality data, since the goal of the meta-analysis is to see if there is any difference in mortality
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What we see is a 62% reduction in the relative risk of dying among covid patients treated with ivermectin. That would mean that ivermectin prevents roughly three out of five covid deaths. The reduction is statistically significant (p-value 0,004). In other words, the weight of evidence supporting ivermectin continues to pile up. It is now far stronger than the evidence that led to widespred use of remdesivir earlier in the pandemic, and the effect is much larger and more important (remdesivir was only ever shown to marginally decrease length of hospital stay, it was never shown to have any effect on risk of dying).
I understand why pharmaceutical companies don’t like ivermectin. It’s a cheap generic drug. Even Merck, the company that invented ivermectin, is doing it’s best to destroy the drug’s reputation at the moment. This can only be explained by the fact that Merck is currently developing two expensive new covid drugs, and doesn’t want an off-patent drug, which it can no longer make any profit from, competing with them.
While randomized trials are certainly the gold-standard for determining if you should give a new drug to treat an arbitrary disease, that process is far too conservative during a pandemic where a huge majority of the world cannot access proper medical care. Ivermectin is already massively produced, used throughout the world, and cheap to manufacture (compared to new anti-Covid drugs). Even months ago before the benefits were known, the risks of taking the drug were very small, especially when the treatment guidelines were to do practically nothing.
Still, the many pieces of non-randomized evidence can still clearly point towards this drugs efficacy. The sudden drop in Covid cases in India as the clearest indicator to me.
Ivermectin has been trialed also and has been available on experimental basis even in Europe - and it was found ineffective and is not recommended anymore.
Also similar non-randomized evidence was strongly suggesting that hydroxychloroquine was very effective (e.g. Raoult in France) - until proper randomized trials found it was not effective at all.
So you really can't rely on such evidence. That someone gets better after they got some drug doesn't automatically mean they got better because of the drug. In the absence of controls for other factors (other drugs, spontaneous recovery on their own, etc.) it only means that the drug didn't make their affliction worse.
Not everything has to be immediately a conspiracy of big pharma (or worse).
I read the french research at the time, and it was immediately obvious that it was deeply flawed. Asking around in more expert circles, that did seem to be the uniformly echoed initial reaction even then, from day 1 (not that that means it couldn't have worked, just that the paper that sparked it all was not convincing, at all - but absence of evidence isn't strong evidence of absence in such cases). In retrospect it seems obvious people were looking for some kind of light at the end of the tunnel, and too willing to ignore the warning signs.
The case for ivermectin is not a slam dunk. But it's definitely surpassed the low bar that HCQ set. There is at least quite a lot of suggestive correlation without trivially obvious other explanations, and the data set isn't just "a few people non-randomly selected".
To my non expert opinion the ivermectin case seems at least plausible, whereas HCQ was clearly and obviously nonsense. Still, I'm skeptical, partly precisely because there still hasn't been a slam dunk study and because quite a few proponents seem to have a worryingly conspiratorial view of the world. Stuff like assuming it's not being pushed because it's off patent screams conspiratorial thinking to me, and you hear that quite a lot. And that's a warning sign, because there are quite a lot of interested parties here that really don't care about some pharmaceutical companies profit, and in any case - just because they don't fund it doesn't mean they'll go all Machiavellian and intentionally prolong the pandemic just to sell a future drug, and actually get away with it to boot. At best, the lack of exclusivity might explain why there isn't a specific corporate backer for this research, but it doesn't explain why all of the governments and universities and hospitals etc aren't finding convincing data. So when people see a conspiracy here, I wonder how rationally they're looking at the evidence for Ivermectin, too - and at the end of the day, I'm just a random worried person without the capacity to deeply understand every single relevant bit of data, so I need to be able to find trustworthy sources and research. People that see conspiracies everywhere (without data and without real reason) don't inspire great trust in their analyses.
Still, it's hard to resist the lure of the cheap and affordable silver bullet...
The López-Medina trial was one of the biggest RCTs for Ivermectin. Out of the 60 trials for Ivermectin, it was one of the few that didn't show statistical significance.
It was also seriously flawed - a large percentage of the placebo group was self-medicating using Ivermectin, they mixed up the treatment and placebo group, and they switched the primary outcome in the middle of the trial. That trial still showed improvement, but it didn't reach statistical significance.
"[López-Medina] has many issues. The primary outcome was changed mid-trial from clinical deterioration to complete resolution of symptoms including "not hospitalized and no limitation of activities" as a negative outcome. Critically, temporary side effects of a successful treatment may be considered as a negative outcome, which could result in falsely concluding that the treatment is not effective. Such an outcome is also not very meaningful in terms of assessing how treatment affects the incidence of serious outcomes. With the low risk patient population in this study, there is also little room for improvement - 58% recovered within the first 2 days to "not hospitalized and no limitation of activities" or better. There was only one death (in the control arm). This study also gave ivermectin to the control arm for 38 patients and it is unknown if the full extent of the error was identified, or if there were additional undiscovered errors. The side effect data reported in this trial raises major concerns, with more side effects reported in the placebo arm, suggesting that more placebo patients may have received treatment. Ivermectin was widely used in the population and available OTC at the time of the study. The study protocol allows other treatments but does not report on usage. The name of the study drug was concealed by refering to it as "D11AX22". The presentation of this study also appears to be significantly biased. While all outcomes show a benefit for ivermectin, the abstract fails to mention that much larger benefits are seen for serious outcomes, including the original primary outcome, and that the reason for not reaching statistical signficance is the low number of events in a low risk population where most recover quickly without treatment."
I had the same opinion until my friend convinced me otherwise. The scientific community is taking a long-term approach here. If they were to recommend a drug based without a scientific trial, they risk losing the trust of the world (either from people who want them to only follow the science, and the risk that it is incorrect).
The anti-science block is growing, and they are loud. If they continue to grow it could be an even greater threat to humanity than COVID-19. Science is attempting to fight against it by retreating to a science-only corner, for better or for worse.
It would be nice if we somehow found a way as society to get the message out that scientists often just don't know. Because too often stories like this are interpreted by quite a few people as "science says ivermectin doesn't work". And perhaps that conclusion will turn out to be right, but the point is the jury is still out - and often enough it turns out wrong, and when such a false statement turns out to be wrong, people lose faith in science regardless, even though a reasonable interpretation of the science actually said "don't know" not "doesn't work".
This is kind of a corollary to the issues with rejecting conspiracies - when we reject a supposed conspiracy, due to lack of evidence, that can easily come across as claiming the conspiratorial claim is outright false - but in a sea of such claims, some then turn out to have at least a kernel of truth, which then turns into a big gotcha moment: "see, they're repressing us, we were right all along!"
So while I understand the idea of maintaining trust by not backing anything uncertain, I'm not sure it's the right call. Maybe communicating that uncertainty is better, and even communicating hints and possibilities - instead of trying to control the narrative but thereby ceding the ground to nutjobs until certainty arrives, often granting them considerable prestige if they guess sort of correctly ahead of time.
> The sudden drop in Covid cases in India as the clearest indicator to me.
What's the alleged connection here? Are you claiming that some non-trivial number of patients in India were treated with this? How many, and at what point after being infected? And just how did the treatment affect the case numbers? Generally you'd expect the vast majority of secondary infections to happen before the diagnosis, not after, so a treatment seems totally irrelevant to the case numbers.
Not a primary source, so FWIW. The article compares states in India using ivermectin against those which are not. Some digging in the sources listed might get what you are looking for.
I see no numbers on how many people were treated on either of the first two links, and certainly don't intend to comb through the dross on the third link. So do you actually have a number? It doesn't need to be exact, just a credible source on the order of magnitude will be enough. Are we talking a thousand, a million, or a billion here?
To reduce R by a factor of 2 by the use of a prophylactic drug, you'd need to have half of the population on a regime of the drug. It seems pretty obvious that did not happen if this kind of reporting is the most impactful there is. Just think of the logistics of trying to do that! India has a population of 1.4 billion.
On the other hand, if they only gave the snakeoil to e.g. a single digit number of millions of people the reduction in the number of infections would be imperceptible.
This is a great comment, and an example of why discussion of ivermectin should not be CENSORED but instead debated. These would be good questions to ask the creators of any videos on the topic and from what I can see, the most popular creators would probably be open to the discussion.
Its the governments of the two states that are making the claims in the news articles.
I think it is safe to suppose they or the associated medical authorities have observed a big enough benefit before making that claim.
But no, no concrete numbers, as I think there was not much of tracking the number of patients who were given the drug. May be it is because such numbers are not much of a value in terms of research data due to lack of controls.
>India wouldn't have taken it off the recommended drugs list.
Normally authorities are afraid to go against W.H.O recommendations, because if it didn't work out, it would be hard to justify it on the basis of local observations alone, at least on paper.
But the important thing is that some states still did it, which might indicate there was very observable benefit.
Wait a minute... This post is a debate between two opposing viewpoints. So it also makes the exact opposite point:
The primary difference between a randomized controlled trial and meta-analysis is that the former “provide the highest level of evidence because they contain the least amount of bias. Randomized controlled trials reduce bias, while meta-analyses increase bias."
This Hacker News story is about a recent meta-analysis. But an actual randomized control trial of Ivermectin in March (on 476 patients) found the duration of symptoms on treated and untreated patients "was not significantly different."
Important thing to know about that study is they are testing time to recovery for people with mild covid.
I'm not anywhere near an expert, but two things stood out to me reading this study. First, time to recover in the ivermectin group was 10 days versus 12 in the placebo. The paper calls this "not significant" but it's not clear to me whether that's statistically not significant, and if so, why wouldn't it be, or if knocking two days off recovery isn't that meaningful. The other thing I noticed reading it was that only one person out of 400 died and that person was in the placebo group.
I think the Brett Weinstein response would be something like -
A. Ivermectin's best benefit is as a prophylactic not a treatment.
B. Ivermectin should be administered as early after onset as possible to treat, whereas here there was some delay to get people organized, enrolled in trial, etc.
C. It's hard to measure effect when the disease is mild.
I didn't see the standard deviation reported in the paper. Is it?
I did see the innerquartile range and it was the same for both the ivermectin group and the placebo. To me that suggests that variation in outcomes is probably similar between the two groups.
"hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]"
So statistically, those on ivermectin recovered 1.07 times as quickly as those on placebo, but the uncertainty bounds are from 0.87 times as fact to 1.32 times as fast.
Does that mean that the covid vaccines shouldn't be recommended as there's no randomized trials on their long-term effects? Just curious as I'm not well versed on this topic.
Covid vaccines have been tested with randomized trials (Phase 3 of the testing phase). Regarding "long-term", that obviously depends on how you define "long-term but there is no need to move the goalpost.
Generally speaking, in evidence-based medicine drugs and vaccines are not recommended based on incomplete statistics or hunches.
