36 ms·

Lesson of ivermectin: meta-analyses based on summary data alone are unreliable

217 points by 4512124672456 5y ago

eigengrau5150 5y ago
I've suspected that for years. I remember my undergrad biology prof coming down on students depending on meta-analysis and insisting they were no substitute for attempting to replicate the experiments themselves.
- dekhn 5y ago
  that doesn't make scientific sense. Replicating the original experiment and doing a meta-analysis have two completely different goals. I would have argued that back to the professor (and been right).
  - gorwell 5y ago
    How useful is meta analysis if half or more of the experiments don't replicate? As we increasingly discover with the replication crisis.
    - dekhn 5y ago
      Medical studies can't be replicated in experiments. They are almost always one-shot. That's not how medical studies (that we do meta analysis) work. It's too expensive and too complicated.
    - buescher 5y ago
      Bingo. Also the problem with meta-analysis of certain kinds of studies (say, observational ones) is the file-drawer effect: people don't report negative results. So you can go from a bunch of studies that show an effect (usually small) at marginal statistical significance to a meta-analysis that shows very high statistical significance when there is really no effect there. I don't think we have to worry about the file-drawer effect much with controversial COVID treatments, though. Do you?
    - dekhn 5y ago
      I said they had different goals, not that they don't overlap. If you're in a class teaching medical studies, and you tell people "go replicate the original experiment instead of doing meta analysis", you're doing your students a disservice. Instead say: "It's always important to be able to replicate experiments and I encourage everybody in the class who is going on to do science or medicine spend at least some time in the lab replicating a basic experiment. But medical studies are so large and complicated that we can't typically repeat them in a reproducible way. Instead, we use statistics and probability to make reasonable decisions based on the data we have. Sometimes that means removing a suspect paper from a meta-analysis because we lack confidence in its reproducibility." For some of the most sophisticated medical science experiments we have today, the only way to replicate an experiment is to be a postdoc and join the lab that does the research, master the technique there, then take your reagents and other material to your professor job, and then get your local set up to replicate what you did in the original lab. This is how it normally works, for example in labs like Mina Bissell's where few people in the work even have the skills to replicate her experiments.
  - marcodiego 5y ago
    Hmmm... How about meta-analysis considering only results that were successfully replicated? Why not consider an index that is higher with the number of successful replications and lower of number of replication tries?
- simonh 5y ago
  Ok you replicate the original study. Presumably you want to use this new result to increase your statistical power compared to the original result, combining the results of the two studies.... which... is.. er... meta analysis. The whole point of meta analysis is that you have multiple studies of the same experiment.
motoboi 5y ago
Someone said it and I totally agree: Society is not ready to watch science in realtime.
- greenonions 5y ago
  I agree, though there are two obvious courses of action that result from this: 1. Prevent the viewing 2. Increase the readiness Of which I think #2 is most preferable.
  - dataduck 5y ago
    Perhaps, but unfortunately #1 is more realistic.
    - evv555 5y ago
      Decaying trust in medical institutions says otherwise.
    - colordrops 5y ago
      Hiding science from the public has got to be one of the worst suggestions I've ever heard on this site.
  - toss1 5y ago
    #2 is for sure bviously preferable, but Good Luck With That. Once you get below the top N% in intelligence levels (5%-20% in my experience), the ability to 1) understand any kind of complex systems, 2) read, understand, contextualize and retain data, and maintain any rigorous logical thinking structure (e.g., keeping previously eliminated options eliminated) declines rapidly. The result is that, despite having absolute record numbers and percentages of people educated with college degrees, we have massive anti-science movements that are literally killing thousands of people daily, by ape-ing scientific-sounding terms & distorting concepts & data in order to more effectively broadcast disinformation - and hordes lap it up. We even have nurses and healthcare workers, who supposedly have been taught and passed tests on basic germ theory, actively resisting and campaigning against safe and effective public health measures. A related phenomenon is that college degrees are systematically being degraded. I personally know someone who was a visiting professor at a US State University, teaching introductory economics. He found that many of the students didn't even have the math skills (or motivation) to understand and wield the basic concepts on assignments, classroom discussion, and tests, and of course he was recommending them to remedial options and failing them. He was explicitly ordered by the administration to pass them or quit. He quit. Sadly, it is looking more and more like this great experiment in college for all is not working out as hoped. Instead of a culture of wisdom, we have a culture of sophomores - literally wise fools, who know very little, but think they know it all, and therefore don't have to listen to any expert who actually has real knowledge. It is considered obvious that at 5'6"/168cm, I was not born with the attributes necessary to engage in a professional basketball career. Yet the same kind of sorting based on intelligence is considered something to not discuss, perhaps getting too close to eugenics. I strongly believe that the opportunity should exist for any person to get whatever level education they want, without financial or other obstacles. But, with the caveat that it cannot be dumbed-down - either you can understand and do the work and pass, or you do not. The practices seen above, and grade inflation in general need to be reset. The problem is that failing your students is bad for business, so unlikely that most colleges will reform.
nradov 5y ago
Yes the quality of scientific research in this area has been rather bad with rushes to publish and ineffective peer review. Drs. Paul Marik and Pierre Kory recently updated their meta analysis to remove the retracted Elgazzar paper, and still found a significant effect. I'm not endorsing their letter, just pointing out that it exists and isn't mentioned in this Nature article. https://journals.lww.com/americantherapeutics/fulltext/2021/10000/ivermectin,_a_reanalysis_of_the_data.9.aspx https://journals.lww.com/americantherapeutics/fulltext/2021/... Ultimately we need a real large scale controlled trial to settle the issue so I'm looking forward to seeing results from NIH ACTIV-6. https://www.nih.gov/research-training/medical-research-initiatives/activ/covid-19-therapeutics-prioritized-testing-clinical-trials#activ6 https://www.nih.gov/research-training/medical-research-initi...
- saalweachter 5y ago
  That meta-analysis still includes the Carvallo studies, which some people have doubts about: https://www.buzzfeednews.com/article/stephaniemlee/ivermectin-covid-study-suspect-data https://www.buzzfeednews.com/article/stephaniemlee/ivermecti...
- cageface 5y ago
  This article also says that another trial that were included in previous meta-analyses should probably also be excluded and once all that's it's unlikely the meta-analysis will show an effect: As these two papers1,6 were the only studies included in that meta-analysis to demonstrate an independently significant reduction in mortality, the revision will probably show no mortality benefit for ivermectin.
- tptacek 5y ago
  This letter opens with a defense of the ElGazzar paper, but the analyses published by these researchers strongly suggests that the paper is indefensible and likely a simple fraud. I'm skeptical.
- Spellman 5y ago
  Looking at the two papers (original, and updated) they only removed the Elgazzer paper but not the contested Shakhsi Niaee also mentioned in the Nature article. This is noteworthy because it's also the only other RCT to show strong effect on mortality (see Fig3 in the two papers). Original Marik, Kory paper Fig3 is here: https://pubmed.ncbi.nlm.nih.gov/34375047/#&gid=article-figures&pid=figure-3-uid-2 https://pubmed.ncbi.nlm.nih.gov/34375047/#&gid=article-figur... Also, the Nature article is concerned that the underlying data isn't sound due to bad randomization and thus naive meta-analysis is inherently flawed in these cases.
ndr 5y ago
Mind that this is correspondence, not a peer reviewed paper. For what is worth most meta-study will check if they reach the same results leaving-n out (typically one), but I agree that they could do much better accessing the underlying data itself.
gonational 5y ago
Because there are so many studies of ivermectin and because it is so widely used, of course there are going to be bunk studies and scientifically invalid studies. Do you know how I know this? I know this because it was recently shown (within the past ten years) that something like 70% of scientific studies can't be reproduced (read: they're BS). So if were going to use scientific studies at all, to inform our decisions, as a society, then we have to accept that there's going to be flaws in some of them. And if we know that there are flaws in some of them, we can also conclude that a large quantity of corroborating studies is as important as the scale of each individual study. The same applies to meta-analyses. For example, it's going to be pretty difficult to publish over 100 studies[1] that all corroborate the almost-same set of basic facts, and then have all +100 of them be completely invalid. However, having over 100 different studies of a 50-year old medicine, from different scientists in different parts of the world based on different data sets over different spans of time and under different circumstances, and having the data corroborate the same key facts and numbers, I would trust this any day over a government funded study of a brand new medicine that is in a brand new category of medicines which has never been used in history. There are literally hundreds of studies at this point proving that ivermectin is safe and effective for treating many things, including influenza and coronavirus, including COVID-19. There are literally no studies proving that the Pfizer or Moderna gene therapies are safe and effective, or even that they are safe or effective, at both treating and preventing the spread of COVID-19. The latter of the two is the most important in the debate over whether people should be forced to take said medicines. And it is the inverse of that which has been proven through many studies now. 1. https://c19ivermectin.com/ https://c19ivermectin.com/
- dreyfan 5y ago
  I think you’re late for your chiropractor appointment.
- creddit 5y ago
  > There are literally no studies proving that the Pfizer or Moderna gene therapies are safe and effective, or even that they are safe or effective, at both treating and preventing the spread of COVID-19. This is... wildly incorrect.
gambler 5y ago
So, they demand to change an established scientific practice because they don't like the results it produced in a particular case. And then everyone wonders why people no longer "trust the science".
- nostoc 5y ago
  Is meta analysis of unpublished result really such an established scientific practice?
  - tptacek 5y ago
    I think you're dignifying this comment, which objects to the authors request that meta-studies not include fraudulent analyses in their inputs as an unwarranted "change to established practice".
  - gambler 5y ago
    From the article you're commenting on: "We recognize that this is a change to long-accepted practice and is substantially more rigorous than the standards that are typically currently applied" Meta-analyses generally follow certain pre-established standards. That's the whole point of such studies. It's one thing to claim that authors of a particular meta-study broke the standards. This is not being claimed here. It's an entirely different thing to claim that the standards themselves are broken and need to be changed generally. This is a huge claim that casts doubt on tons of prior research. Maybe we do need more rigorous rules for meta-analysis. However, if that's the case, it should be true for all research of this type, not just papers examining "interventions for COVID-19" (as the article suggests). Hence, my take on this. It's reasonable to question scientific standards if you are willing to demonstrate that they are really broken. (This was done with p-hacking, for example.) It's not reasonable to say that a specific subject in research should have different evidentiary standards because of controversy around one drug.
- simonh 5y ago
  The asked for the papers to be revised because they found and presented specific clear evidence the data was invalid. If by "don't like results" you mean "don't like clearly invalid and possibly fraudulent results", then yes. Correct.
programmarchy 5y ago
How does the current field of studies compare to Remdesivir? Remdesivir is a repurposed antiviral (originally designed for Ebola) with fairly low efficacy, and very severe side effects, and it breezed through FDA emergency authorization. I don't understand why it seems that the bar is set so low for Remdesivir, but so high for Ivermectin.
- droptablemain 5y ago
  I think you answered your own question -- Remdesivir is an antiviral and Ivermectin is an antiparasite.
  - programmarchy 5y ago
    It's not that simple. For example, a protease inhibitor could have effects on biological functions that exist in viral and parasitic infections. And both Remdesivir and Ivermectin [1] have been observed to have antiviral properties in vitro. [1] https://www.sciencedirect.com/science/article/pii/S0166354220302011 https://www.sciencedirect.com/science/article/pii/S016635422...
    - veemjeem 5y ago
      Many things are effective against covid-19 in-vitro. When it was administered in hamsters, there was no effect on viral load. https://www.biorxiv.org/content/10.1101/2020.11.21.392639v1 https://www.biorxiv.org/content/10.1101/2020.11.21.392639v1
      - programmarchy 5y ago
        I hadn’t seen that paper, but isn’t your statement missing the forest for the trees? If pathology was attenuated, that would help patient recovery, even if viral load wasn’t directly reduced. > Even though ivermectin had no effect on viral load, SARS-Cov-2-associated pathology was greatly attenuated. IVM had a sex-dependent and compartmentalized immunomodulatory effect, preventing clinical deterioration and reducing olfactory deficit in infected animals. Importantly, ivermectin dramatically reduced the Il-6/Il-10 ratio in lung tissue, which likely accounts for the more favorable clinical presentation in treated animals. Our data support IVM as a promising anti-COVID-19 drug candidate.
input_sh 5y ago
https://archive.is/9EVIv https://archive.is/9EVIv
- deleted 5y ago
  [deleted]
  - deleted 5y ago
    [deleted]
twofornone 5y ago
The premature smear of potentially effective medications like HCQ and Ivermectin by scientifically illiterate media is unforgivable. Especially in the case of Ivermectin, given that it has one of the most benign safety profiles of any known drug. There is no excuse. There should have been federally funded widespread trials a year ago, there is no downside. Instead you now have hospitals forbidding off label prescription with threats of termination. None of it makes any sense; people are treating science as though it were a religion, and the safety and efficacy of the vaccines as some sort of core, unquestionable tenet, complete with shaming and excommunication for nonbelievers. All over a virus which has a complication rate on par with a moderate flu year.
- burkaman 5y ago
  There is a federally funded widespread trial, but they take a while to do correctly: https://www.nih.gov/research-training/medical-research-initiatives/activ/covid-19-therapeutics-prioritized-testing-clinical-trials#activ6 https://www.nih.gov/research-training/medical-research-initi... There was also a federally funded trial of hydroxychloroquine last year which has since concluded: https://www.nih.gov/news-events/news-releases/nih-halts-clinical-trial-hydroxychloroquine https://www.nih.gov/news-events/news-releases/nih-halts-clin...
  - sjwalter 5y ago
    And in the meantime, if you buy into the crazed insanity of "pandemic! pandemic! omg we'll all die", then it makes tonnes of sense to treat people with a highly-available, incredibly safe medication that frontline clinicians all over earth are reporting success with, especially a drug that has been dosed ~4 billion times over two generations, that has been most often dosed by illiterate people and delivered by non-doctor NGO workers.
    - burkaman 5y ago
      I guess the reason doctors aren't prescribing Ivermectin is that they don't buy into "crazed insanity" and don't feel the need to try anything that might work. And I can only speak for myself, but the attitude I'm seeing is "a lot of people are dying and we should try to work together as a society to stop that from happening", not "omg we're all gonna die".
lez 5y ago
Looking at the greyed out comments it seems HN is not pro, but against scientific debate. Questioning science IS part of the scientific method. https://c19ivermectin.com/ https://c19ivermectin.com/ is a very adequate counter-argument to the article, and it's unfair to the whole scientific community that comments are greyed out that mention it.
- narrator 5y ago
  I think a certain segment of the population refuses to believe that there would be purposeful suppression of information that could potentially save millions. They will not believe any information that leads to that conclusion no matter what the evidence. Period. Full stop.
- katbyte 5y ago
  ivermectin in the end after all the bad studies were redacted had no affect: https://www.iheart.com/podcast/105-behind-the-bastards-29236323/episode/part-one-the-ivermectin-episode-86648655/ https://www.iheart.com/podcast/105-behind-the-bastards-29236...
rory 5y ago
Ivermectin probably doesn't do anything to fight Covid-19, but the American media has really shown their corruption in the way they've treated it. It's clearly a safe drug to take in human-designed doses, and it's cheap to produce. Laughing at people for poisoning themselves with "horse dewormer" instead of pointing out that they are turning to the vet store because their access to medicine has been marginalized is sick. And maybe it does help, I don't know. Unproven != disproven.
- tptacek 5y ago
  It matters a lot if ivermectin doesn't do anything to stop C19, even if it is otherwise safe (it surely is, dosed professionally). People take ivermectin instead of vaccinating or complying with NPIs. If ivermectin doesn't work, that is a very, very big deal.
  - rory 5y ago
    > People take ivermectin instead of vaccinating or complying with NPIs Doing one thing but not another doesn't imply you're doing one thing instead of another. Do you truly believe the people ODing on ivermectin would be lining up for vaccinations if it didn't exist?
    - myrmidon 5y ago
      Lining up? Not necessarily. But it seems almost certain to me that at least some people feel safe thanks to taking ivermectin (while distrusting mainstream vaccines), and those people would turn eventually to the vaccines if those were the only perceived path towards C19 safety.
      - rory 5y ago
        Perhaps on the margin some would, but I suspect most would fall into the "natural immunity" camp. So in my mind, we need to weigh the damage done by blocking safe ivermectin use for some number of people to the damage done by a much-smaller number of people remaining unvaccinated when they otherwise would get the jab. Seems like it could go either way depending on your specific assumptions.
ashtonkem 5y ago
The other takeaway is that preprint publication is a pathway ripe for abuse. The major paper that drove most of this situation, and the meta analysis, appears to have been a straight up fraud. But it got circulated a lot as a preprint to people who didn’t understand the difference between a preprint and a peer reviewed paper. If the preprint had been more private, this might have been averted.
- scoopertrooper 5y ago
  What's the motivation for this sort of thing? It seems the very thing they crave (attention) will invariably bring them undone as attention invites scrutiny.
  - avhon1 5y ago
    For one, money. There is an organized group that charges $90 online for hocus-pocus covid medication prescriptions [1]. The more people that can be convinced that this is a worthwhile purchase, the more money they get. https://americasfrontlinedoctors.org/treatments/how-do-i-get-covid-19-medication/ https://americasfrontlinedoctors.org/treatments/how-do-i-get...
    - ashtonkem 5y ago
      That and politics. The frontline group was also involved in the Hydroxychloroquine debacle, and they were selected specifically by political actors as a pro-trump solution to the pandemic. With any of these politically connected things, there’s always a mix of grift, political opportunism, and true believers.
- sjwalter 5y ago
  > The major paper that drove most of this situation, and the meta analysis, appears to have been a straight up fraud. Umm, wat?! The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians. Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs. The evidence for IVM as a treatment for covid (and many other viruses) is quite strong. There is, no, no large-scale RCT for IVM. However, it is inherently obvious that none will happen, none that give it a fair shake. The entire public health apparatus in the West has a huge desire to treat all illness with only on-patent, new medications. Do you not thin that this incentive influences what gets into the news? Do you think the public health authorities in Uttar Pradesh (https://indianexpress.com/article/cities/lucknow/uttar-pradesh-government-says-ivermectin-helped-to-keep-deaths-low-7311786/ https://indianexpress.com/article/cities/lucknow/uttar-prade...) are lying?
EnlightenedBro 5y ago
For those interested to learn more about Ivermectin, watch JRE#1671 podcast episode. Lots of interesting information covered about the drug by 2 biologists. It may change your views on this for the better, or the worse.
- vernie 5y ago
  You're better off if you only associate "JRE" with Java.
  - xdennis 5y ago
    People shouldn't be taking medical advice from JRE (or celebrities (or politicians)), but what's wrong with his podcast?
- veemjeem 5y ago
  Dr. Pierre Kory was one of the main dudes promoting ivermectin -- he references the meta-analysis study on ivermectin that was later redacted. Of course when this interview was released (june 22), the study was not yet redacted (july 14) so it looked like the drug worked far better all the drugs including steroids & antibody treatment.
buescher 5y ago
The lesson of ivermectin: a lot of medical studies that go uncriticized because they're less controversial probably have problems similar to the problems of the retracted Elgazzar study and the other studies mentioned. Why else would these people think they would get away with it?
gwerbret 5y ago
I'm going to make what is probably a controversial statement, which is that, in my experience, most meta-analyses are trash. A meta-analysis is usually grounded on the assumption that an aggregation of multiple, well-conducted studies can provide significant information that may not be evident by taking each study individually. Essential to this assumption is the premise that those studies included in the meta-analysis be scientifically rigorous in themselves. Unfortunately, this is almost never the case. The great utility of the meta-analysis in the clinical literature is such that there have emerged a series of standards for how to conduct such analyses, such as controlling for bias, controlling for variability, etc. These seldom include actual assessment of the scientific quality of the studies, as this is harder to standardize. Consequently, there is a preponderance of meta-analyzes that come to conclusions that are simply not justified, because the studies themselves were not scientifically rigorous. I believe this applies to the situation of ivermectin, and it just so happens that this is the thrust of the point raised in the Nature article cited here.
- tantalor 5y ago
  FiveThirtyEight weights its averages by pollster accuracy/methodology. Next, we determine how much weight to give each poll in our average. First, polls conducted by pollsters with higher FiveThirtyEight pollster ratings — a letter grade measuring how accurate and methodologically sound pollsters are — are given more weight https://fivethirtyeight.com/features/how-were-tracking-joe-bidens-approval-rating/ https://fivethirtyeight.com/features/how-were-tracking-joe-b...
  - nradov 5y ago
    There is no equivalent feedback mechanism in medical research. Other than looking for retracted papers, we don't have a reliable way to quantify whether a particular author is "correct" more often than another.
    - antman 5y ago
      The author’s Hindex could be an initial weighting factor
mechE321 5y ago
The Bayesian gambler in me wants to think this: The studies on ivermectin seem to be split between "good effect" and "no effect," and there don't seem to be any (by my extremely informal review! going off of memory here) in the camp of "bad effect." Seems reasonable to take ivermectin as a decent gamble to me while we wait on the dang science to get its head out of its butt.
- simpleguitar 5y ago
  If iver is a good gamble, then wouldn't the vaccine be a better gamble? After all, unlike iver, there is very good hospitalization data about vaccinated vs unvaccinated now.
  - rory 5y ago
    This is true, but just because the two are on opposite sides of the culture war doesn't mean they're medically mutually exclusive.
    - simpleguitar 5y ago
      Actually, it does. The only reason one would be taking iver prophylactically, is because one wasn't vaccinated. And the only reason to take iver after covid symptoms develop is because you didn't take the vaccine. If one was vaccinated and are feeling sick enough to take iver, she would be better off with oxygen and hospital SOC.
      - rory 5y ago
        It seems like you're just saying you don't believe ivermectin works? That's fine and likely correct, but logically it's completely unrelated to its mutual exclusivity to the vaccine. For instance, if you get tetanus after having the vaccine, you'll still be given antibiotics. If someday ivermectin is proven to have a positive effect against Covid, we won't withhold it from vaccinated patients.
      - bongcloud420 5y ago
corona-research 5y ago
You shall have no other medicine besides me.
hackingforfun 5y ago
With all the criticism of the mRNA and other COVID vaccines, which actually do have science backing them up, what is the science that would make ivermectin actually work? It's an antiparasitic drug. I see a lot of criticism of the COVID vaccines, especially from the right, but then they are fine taking hydroxychloroquine or ivermectin if there is any glimmer of hope that they will work. I just don't get it. Maybe, just maybe, it's not all some big conspiracy, and the vaccines were actually designed to help people? Is that so far fetched? Doesn't taking something random like hydroxychloroquine or ivermectin seem more far fetched? It does to me.
- tzs 5y ago
  Here is an article from May 2020 about 15 drugs [1], including hydroxychloroquine and ivermectin, that were being looked into to see if they might help COVID. It goes into the mechanisms that led researchers to believe they were worth looking at. [1] https://www.nature.com/articles/d41591-020-00019-9 https://www.nature.com/articles/d41591-020-00019-9 Edit: Oops...forgot to link the article. Added.
  - deleted 5y ago
    [deleted]
  - hackingforfun 5y ago
    Interesting, thanks.
    - winocm 5y ago
      I really don't want to go back rehashing the point as to why it doesn't work, mainly because finding all of the references again and double checking the wording to make sure it matches the literature is rather time consuming... https://news.ycombinator.com/item?id=28544765 https://news.ycombinator.com/item?id=28544765
      - hackingforfun 5y ago
        I'm not saying they do work. I just appreciated the reference and thought it was interesting to read through. I am pro-vaccine and think that is the most effective course of action. Anyway, thanks for the link to your other post.
defaultprimate 5y ago
Studies are irrelevant at this point, when we have population level data of over a billion people across India and Africa, and the massive disparities between states/countries that utilized Ivermectin, and those that did not. The drug is safe enough to be used based on this data alone. https://www.thedesertreview.com/opinion/columnists/indias-ivermectin-blackout/article_e3db8f46-f942-11eb-9eea-77d5e2519364.html https://www.thedesertreview.com/opinion/columnists/indias-iv... https://www.thedesertreview.com/news/national/indias-ivermectin-blackout-part-ii/article_a0b6c378-fc78-11eb-83c0-93166952f425.html https://www.thedesertreview.com/news/national/indias-ivermec... https://www.thedesertreview.com/opinion/columnists/indias-ivermectin-blackout---part-iii-the-lesson-of-kerala/article_ccecb97e-044e-11ec-9112-2b31ae87887a.html https://www.thedesertreview.com/opinion/columnists/indias-iv... https://www.thedesertreview.com/opinion/columnists/indias-ivermectin-blackout---part-iv-keralas-vaccinated-surge/article_8a8c481c-09d3-11ec-a51c-fb063e1a3e3b.html https://www.thedesertreview.com/opinion/columnists/indias-iv... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968425/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968425/ https://journals.lww.com/americantherapeutics/fulltext/2021/06000/review_of_the_emerging_evidence_demonstrating_the.4.aspx https://journals.lww.com/americantherapeutics/fulltext/2021/...
- walterbell 5y ago
  At this point, news articles should include a bar chart for health interventions, including a three year projection of vendor revenue, tax costs, quality-adjusted life years, societal collateral damage, and risks based on prior usage. When one option has billions of revenue at stake, investors will pay for more/focused studies vs an option to reuse low-cost generics. Unfortunately, or fortunately, desperate humans have skipped trials of both vaccines and early treatments, so there is data on both.
- NotSammyHagar 5y ago
  If you are fixated on conspiracy claims against your amazing scientific discovery - pretty much you are always wrong, that's true for perpetual motion machines, faster than light drives (that's the one I hope could be right), extra-ordinary life extensions for microbes applies to humans (wish that one could be right), and covid. If you use opinion columns from obscure news sources to prove you are right, almost always wrong too. Ivermectin is safe enough to take, the important question is does it do any good against covid. At best it doesn't hurt you and it's unclear, but probably does nothing. It's certain there is no international pharmaceutical conspiracy trying to block discussion of it. That's different than trying to avoid showing incorrect medical information to people during a worldwide medical emergency. The hospitals in my state are full of idiotic non-vaxed covid victims. The latest thing is a conspiracy that the hospital won't treat them with ivermectin because they want them to die. People are just killing themselves because of their bizarre and irrational resistance to safe, life-saving vaccinations and preference for random spoutings on the internet to research proven treatments. Do people challenge their math professors in college because they don't consult fox news for the truth? No. I don't have much hope for our future when we can't get these simple things right. It's like a new dark ages has come upon us. But the truth is we humans were always this foolish.
The_rationalist 5y ago
https://ivmmeta.com/ https://ivmmeta.com/
atty 5y ago
What I find almost more interesting than the article itself is the comments that show a non-zero portion of the HN community (which I think is generally more intellectually curious and educated than average) are actually strongly arguing that ivermectin has strong effect, and even crazier, that it may be safer or more effective than the mRNA vaccines. Is this from being incapable of following science and drawing rational conclusions? Or is it more of a tribal thing, where they are exposed to a biased subset of information/misinformation, and are now emotionally invested in the success of ivermectin because their tribe is? Either way, like someone else in the comments said, these past 2 years have shown us that laypeople are incapable of following active science in real time and drawing reasoned conclusions. Frankly, this is probably true of everyone who is not an expert in the field in question. We need organizations like the CDC and FDA to be much better about their messaging (remember the no-mask debacle? Great way to lose credibility, guys and gals), and we need much better tools to shut down the spread and weaponization of misinformation from the anti-vax crowd et al. I honestly don’t have any idea of how either of those get fixed, however.
- rajin444 5y ago
  Your post is assuming a lot of this science is "settled". I don't think science is settled - especially in this field. Acknowledging that your own statements may be incorrect might help you down the path to figuring out a fix. Hint: as soon as you know you're right, and you make statements based on that, when you're inevitably wrong (not saying this in a disparaging way - making sense and being right through all this is nearly impossible), you will lose all trust.
  - atty 5y ago
    Settled is a strong claim, but as far as I’m aware (I have many connections amongst the medical and epidemiological communities), the general consensus is that ivermectin does not work. For instance, the FDA, WHO, the AMA, the American Pharmacists Association, and the American Society of Health-System Pharmacists all say it should not be used outside of clinical trials because there is no good evidence for it, and even Merck, the manufacturer, specifically states it should not be used for COVID at all. I’m not saying no discourse or testing should happen. I’m a scientist, I believe scientific freedom, and of course, that includes a lot of disagreements. But those disagreements happen in the scientific community, not in the general public. What’s happening in the general public is not at all connected to what’s happening in the research. Instead, I’m interested in how these “treatments” with no strong evidence are getting weaponized by motivated agents (like the anti-vax crowd) to sow distrust both in scientific organizations (the CDC, and the FDA, Pfizer, Moderna, et al), and in the use of tools with proven effectiveness, like the vaccines themselves.
cyounkins 5y ago
There is a lot of confusion on whether there actually was a significant increase in calls to poison control centers due to ingestion of ivermectin. This [1] official Mississippi government document says, "At least 70% of the recent calls have been related to ingestion of livestock or animal formulations of ivermectin purchased at livestock supply centers." But then the AP [2] seemed to say that was incorrect: "The Associated Press erroneously reported based on information provided by the Mississippi Department of Health that 70% of recent calls to the Mississippi Poison Control Center were from people who had ingested ivermectin to try to treat COVID-19. State Epidemiologist Dr. Paul Byers said Wednesday the number of calls to poison control about ivermectin was about 2%. He said of the calls that were about ivermectin, 70% were by people who had ingested the veterinary version of the medicine." Does anyone have additional clarification? [1] https://msdh.ms.gov/msdhsite/_static/resources/15400.pdf https://msdh.ms.gov/msdhsite/_static/resources/15400.pdf [2] https://www.sfgate.com/news/amp/Health-Dept-Stop-taking-livestock-medicine-to-16405982.php https://www.sfgate.com/news/amp/Health-Dept-Stop-taking-live...
- tedunangst 5y ago
  There was an absurd rush to report that ivermectin is bad that resulted in a pretty bad breakdown of the fact checking process. A lot of semi-adjacent facts and statements got merged. A hospital is full and a hospital treated someone for overdose became all the hospitals are filled with overdose victims. (I think eating horse paste is dumb, but that doesn't excuse rolling stone lying about the consequences of doing so.)
  - OrvalWintermute 5y ago
    > A lot of semi-adjacent facts and statements got merged. A hospital is full and a hospital treated someone for overdose became all the hospitals are filled with overdose victims. I thought they said gunshot victims weren't getting treated in some podunk tiny town of less than 10k residents, then they plagiarized a photo to add a racial element, using African Americans, then spread the story everywhere? https://www.msn.com/en-us/news/us/rolling-stone-covid-19-debacle-is-indicative-of-a-larger-problem-in-media/ar-AAOcqzS https://www.msn.com/en-us/news/us/rolling-stone-covid-19-deb...
mgamache 5y ago
And yet the Authors of this letter fail to address the most cited meta-analyses (by Dr Lawrie). She's publicly stated the removing the Elgazzar data did effect her numbers, but not the conclusion. Also, if you read the paper she downgrades the Niaee data for several potential biases. https://pubmed.ncbi.nlm.nih.gov/34145166/ https://pubmed.ncbi.nlm.nih.gov/34145166/
- unanswered 5y ago
  In this polarized world of clickbait headlines, it's never necessary to attack your opponent's strongest argument, only their weakest. (If they don't have a weakest argument you can always publish a straw man as a false flag.) Now the totally true headlines say that ivermectin studies are discredited, and it matters not one jot that the study that was discredited was already of low credibility to begin with and was never a substantial reason for believing one way or the other.
sydthrowaway 5y ago
There is no good faith argument against the vaccine. Just take it.
- brigandish 5y ago
  > First: the opinion which it is attempted to suppress by authority may possibly be true. Those who desire to suppress it, of course deny its truth; but they are not infallible. They have no authority to decide the question for all mankind, and exclude every other person from the means of judging. To refuse a hearing to an opinion, because they are sure that it is false, is to assume that their certainty is the same thing as absolute certainty. All silencing of discussion is an assumption of infallibility. Its condemnation may be allowed to rest on this common argument, not the worse for being common. J. S. Mill wrote the rebuttal to your argument 160+ years ago. He wasn't using it as an anti-vaxx argument either, so it might be time to stop the moralising and simply try to make a persuasive case. I'd wager it's easier without the moralising anyway.
- NaturalPhallacy 5y ago
  >There is no good faith argument against the vaccine. Factually false. 1. It isn't a vaccine. It's a chemical signal to make your body make things. 2. It doesn't have the efficacy against the plethora of variants that all coronaviruses like the cold continuously create. You can still get COVID-19 after being "fully vaccinated". Human beings lack the technology to vaccinate against coronaviruses, including COVID and the cold. 3. It has caused blood clots. And the proteins created cluster in reproductive organs. 4. There are no long term studies of its effects. 5. If it kills your spouse, you can't sue the manufacturer. Stop spreading misinformation about this pseudo-vaccine.
  - brigandish 5y ago
    It seems that the second half of (3), and (5) are myths. https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/covid-19-vaccines-myth-versus-fact https://www.hopkinsmedicine.org/health/conditions-and-diseas...
sunkenvicar 5y ago
The vaccines become less effective over time. Just like other gene therapies which are correctly classified by the FDA as drugs. Mean age of permanent heart damage from the vaccines (DNA or RNA) is 33. No thanks. I will keep taking ivermectin prophylactically based on overwhelming anecdotal evidence from front-line doctors. We know ivermectin is safe because Merck hands it out like candy in the third world. It is 4 billion doses in 40 years safe. I accept the potential unknown risk of frequent long-term use because of the significant likely upsides. My body my choice.
pier25 5y ago
Here in Mexico most doctors are giving Ivermectin to their COVID patients.
X3h7P4icntav 5y ago
The question of whether ivermectin treats Covid19 in humans is utterly independent of vaccines, HCQ, the state of modern science, whether ivermectin treats other diseases, ivermectin's use in animals, politics, any corrupt ivermectin studies (if you ignore them), and the price of cheese on the moon. I have learned there are many idiots among us. Many, many idiots.
- ivm_man 5y ago
  So true...
deleted 5y ago
[deleted]

217 points by 4512124672456 5y ago

I've suspected that for years. I remember my undergrad biology prof coming down on students depending on meta-analysis and insisting they were no substitute for attempting to replicate the experiments themselves.

dekhn 5y ago
that doesn't make scientific sense. Replicating the original experiment and doing a meta-analysis have two completely different goals. I would have argued that back to the professor (and been right).
- gorwell 5y ago
  How useful is meta analysis if half or more of the experiments don't replicate? As we increasingly discover with the replication crisis.
  - dekhn 5y ago
    Medical studies can't be replicated in experiments. They are almost always one-shot. That's not how medical studies (that we do meta analysis) work. It's too expensive and too complicated.
  - buescher 5y ago
    Bingo. Also the problem with meta-analysis of certain kinds of studies (say, observational ones) is the file-drawer effect: people don't report negative results. So you can go from a bunch of studies that show an effect (usually small) at marginal statistical significance to a meta-analysis that shows very high statistical significance when there is really no effect there. I don't think we have to worry about the file-drawer effect much with controversial COVID treatments, though. Do you?
  - dekhn 5y ago
    I said they had different goals, not that they don't overlap. If you're in a class teaching medical studies, and you tell people "go replicate the original experiment instead of doing meta analysis", you're doing your students a disservice. Instead say: "It's always important to be able to replicate experiments and I encourage everybody in the class who is going on to do science or medicine spend at least some time in the lab replicating a basic experiment. But medical studies are so large and complicated that we can't typically repeat them in a reproducible way. Instead, we use statistics and probability to make reasonable decisions based on the data we have. Sometimes that means removing a suspect paper from a meta-analysis because we lack confidence in its reproducibility." For some of the most sophisticated medical science experiments we have today, the only way to replicate an experiment is to be a postdoc and join the lab that does the research, master the technique there, then take your reagents and other material to your professor job, and then get your local set up to replicate what you did in the original lab. This is how it normally works, for example in labs like Mina Bissell's where few people in the work even have the skills to replicate her experiments.
- marcodiego 5y ago
  Hmmm... How about meta-analysis considering only results that were successfully replicated? Why not consider an index that is higher with the number of successful replications and lower of number of replication tries?
simonh 5y ago
Ok you replicate the original study. Presumably you want to use this new result to increase your statistical power compared to the original result, combining the results of the two studies.... which... is.. er... meta analysis. The whole point of meta analysis is that you have multiple studies of the same experiment.

motoboi 5y ago

Someone said it and I totally agree: Society is not ready to watch science in realtime.

greenonions 5y ago
I agree, though there are two obvious courses of action that result from this: 1. Prevent the viewing 2. Increase the readiness Of which I think #2 is most preferable.
- dataduck 5y ago
  Perhaps, but unfortunately #1 is more realistic.
  - evv555 5y ago
    Decaying trust in medical institutions says otherwise.
  - colordrops 5y ago
    Hiding science from the public has got to be one of the worst suggestions I've ever heard on this site.
- toss1 5y ago
  #2 is for sure bviously preferable, but Good Luck With That. Once you get below the top N% in intelligence levels (5%-20% in my experience), the ability to 1) understand any kind of complex systems, 2) read, understand, contextualize and retain data, and maintain any rigorous logical thinking structure (e.g., keeping previously eliminated options eliminated) declines rapidly. The result is that, despite having absolute record numbers and percentages of people educated with college degrees, we have massive anti-science movements that are literally killing thousands of people daily, by ape-ing scientific-sounding terms & distorting concepts & data in order to more effectively broadcast disinformation - and hordes lap it up. We even have nurses and healthcare workers, who supposedly have been taught and passed tests on basic germ theory, actively resisting and campaigning against safe and effective public health measures. A related phenomenon is that college degrees are systematically being degraded. I personally know someone who was a visiting professor at a US State University, teaching introductory economics. He found that many of the students didn't even have the math skills (or motivation) to understand and wield the basic concepts on assignments, classroom discussion, and tests, and of course he was recommending them to remedial options and failing them. He was explicitly ordered by the administration to pass them or quit. He quit. Sadly, it is looking more and more like this great experiment in college for all is not working out as hoped. Instead of a culture of wisdom, we have a culture of sophomores - literally wise fools, who know very little, but think they know it all, and therefore don't have to listen to any expert who actually has real knowledge. It is considered obvious that at 5'6"/168cm, I was not born with the attributes necessary to engage in a professional basketball career. Yet the same kind of sorting based on intelligence is considered something to not discuss, perhaps getting too close to eugenics. I strongly believe that the opportunity should exist for any person to get whatever level education they want, without financial or other obstacles. But, with the caveat that it cannot be dumbed-down - either you can understand and do the work and pass, or you do not. The practices seen above, and grade inflation in general need to be reset. The problem is that failing your students is bad for business, so unlikely that most colleges will reform.

nradov 5y ago

Yes the quality of scientific research in this area has been rather bad with rushes to publish and ineffective peer review. Drs. Paul Marik and Pierre Kory recently updated their meta analysis to remove the retracted Elgazzar paper, and still found a significant effect. I'm not endorsing their letter, just pointing out that it exists and isn't mentioned in this Nature article. https://journals.lww.com/americantherapeutics/fulltext/2021/10000/ivermectin,_a_reanalysis_of_the_data.9.aspx https://journals.lww.com/americantherapeutics/fulltext/2021/... Ultimately we need a real large scale controlled trial to settle the issue so I'm looking forward to seeing results from NIH ACTIV-6. https://www.nih.gov/research-training/medical-research-initiatives/activ/covid-19-therapeutics-prioritized-testing-clinical-trials#activ6 https://www.nih.gov/research-training/medical-research-initi...

saalweachter 5y ago
That meta-analysis still includes the Carvallo studies, which some people have doubts about: https://www.buzzfeednews.com/article/stephaniemlee/ivermectin-covid-study-suspect-data https://www.buzzfeednews.com/article/stephaniemlee/ivermecti...
cageface 5y ago
This article also says that another trial that were included in previous meta-analyses should probably also be excluded and once all that's it's unlikely the meta-analysis will show an effect: As these two papers1,6 were the only studies included in that meta-analysis to demonstrate an independently significant reduction in mortality, the revision will probably show no mortality benefit for ivermectin.
tptacek 5y ago
This letter opens with a defense of the ElGazzar paper, but the analyses published by these researchers strongly suggests that the paper is indefensible and likely a simple fraud. I'm skeptical.
Spellman 5y ago
Looking at the two papers (original, and updated) they only removed the Elgazzer paper but not the contested Shakhsi Niaee also mentioned in the Nature article. This is noteworthy because it's also the only other RCT to show strong effect on mortality (see Fig3 in the two papers). Original Marik, Kory paper Fig3 is here: https://pubmed.ncbi.nlm.nih.gov/34375047/#&gid=article-figures&pid=figure-3-uid-2 https://pubmed.ncbi.nlm.nih.gov/34375047/#&gid=article-figur... Also, the Nature article is concerned that the underlying data isn't sound due to bad randomization and thus naive meta-analysis is inherently flawed in these cases.

ndr 5y ago

Mind that this is correspondence, not a peer reviewed paper. For what is worth most meta-study will check if they reach the same results leaving-n out (typically one), but I agree that they could do much better accessing the underlying data itself.

gonational 5y ago

Because there are so many studies of ivermectin and because it is so widely used, of course there are going to be bunk studies and scientifically invalid studies. Do you know how I know this? I know this because it was recently shown (within the past ten years) that something like 70% of scientific studies can't be reproduced (read: they're BS). So if were going to use scientific studies at all, to inform our decisions, as a society, then we have to accept that there's going to be flaws in some of them. And if we know that there are flaws in some of them, we can also conclude that a large quantity of corroborating studies is as important as the scale of each individual study. The same applies to meta-analyses. For example, it's going to be pretty difficult to publish over 100 studies[1] that all corroborate the almost-same set of basic facts, and then have all +100 of them be completely invalid. However, having over 100 different studies of a 50-year old medicine, from different scientists in different parts of the world based on different data sets over different spans of time and under different circumstances, and having the data corroborate the same key facts and numbers, I would trust this any day over a government funded study of a brand new medicine that is in a brand new category of medicines which has never been used in history. There are literally hundreds of studies at this point proving that ivermectin is safe and effective for treating many things, including influenza and coronavirus, including COVID-19. There are literally no studies proving that the Pfizer or Moderna gene therapies are safe and effective, or even that they are safe or effective, at both treating and preventing the spread of COVID-19. The latter of the two is the most important in the debate over whether people should be forced to take said medicines. And it is the inverse of that which has been proven through many studies now. 1. https://c19ivermectin.com/ https://c19ivermectin.com/

dreyfan 5y ago
I think you’re late for your chiropractor appointment.
creddit 5y ago
> There are literally no studies proving that the Pfizer or Moderna gene therapies are safe and effective, or even that they are safe or effective, at both treating and preventing the spread of COVID-19. This is... wildly incorrect.

gambler 5y ago

So, they demand to change an established scientific practice because they don't like the results it produced in a particular case. And then everyone wonders why people no longer "trust the science".

nostoc 5y ago
Is meta analysis of unpublished result really such an established scientific practice?
- tptacek 5y ago
  I think you're dignifying this comment, which objects to the authors request that meta-studies not include fraudulent analyses in their inputs as an unwarranted "change to established practice".
- gambler 5y ago
  From the article you're commenting on: "We recognize that this is a change to long-accepted practice and is substantially more rigorous than the standards that are typically currently applied" Meta-analyses generally follow certain pre-established standards. That's the whole point of such studies. It's one thing to claim that authors of a particular meta-study broke the standards. This is not being claimed here. It's an entirely different thing to claim that the standards themselves are broken and need to be changed generally. This is a huge claim that casts doubt on tons of prior research. Maybe we do need more rigorous rules for meta-analysis. However, if that's the case, it should be true for all research of this type, not just papers examining "interventions for COVID-19" (as the article suggests). Hence, my take on this. It's reasonable to question scientific standards if you are willing to demonstrate that they are really broken. (This was done with p-hacking, for example.) It's not reasonable to say that a specific subject in research should have different evidentiary standards because of controversy around one drug.
simonh 5y ago
The asked for the papers to be revised because they found and presented specific clear evidence the data was invalid. If by "don't like results" you mean "don't like clearly invalid and possibly fraudulent results", then yes. Correct.

programmarchy 5y ago

How does the current field of studies compare to Remdesivir? Remdesivir is a repurposed antiviral (originally designed for Ebola) with fairly low efficacy, and very severe side effects, and it breezed through FDA emergency authorization. I don't understand why it seems that the bar is set so low for Remdesivir, but so high for Ivermectin.

droptablemain 5y ago
I think you answered your own question -- Remdesivir is an antiviral and Ivermectin is an antiparasite.
- programmarchy 5y ago
  It's not that simple. For example, a protease inhibitor could have effects on biological functions that exist in viral and parasitic infections. And both Remdesivir and Ivermectin [1] have been observed to have antiviral properties in vitro. [1] https://www.sciencedirect.com/science/article/pii/S0166354220302011 https://www.sciencedirect.com/science/article/pii/S016635422...
  - veemjeem 5y ago
    Many things are effective against covid-19 in-vitro. When it was administered in hamsters, there was no effect on viral load. https://www.biorxiv.org/content/10.1101/2020.11.21.392639v1 https://www.biorxiv.org/content/10.1101/2020.11.21.392639v1
    - programmarchy 5y ago
      I hadn’t seen that paper, but isn’t your statement missing the forest for the trees? If pathology was attenuated, that would help patient recovery, even if viral load wasn’t directly reduced. > Even though ivermectin had no effect on viral load, SARS-Cov-2-associated pathology was greatly attenuated. IVM had a sex-dependent and compartmentalized immunomodulatory effect, preventing clinical deterioration and reducing olfactory deficit in infected animals. Importantly, ivermectin dramatically reduced the Il-6/Il-10 ratio in lung tissue, which likely accounts for the more favorable clinical presentation in treated animals. Our data support IVM as a promising anti-COVID-19 drug candidate.

input_sh 5y ago

https://archive.is/9EVIv https://archive.is/9EVIv

deleted 5y ago
[deleted]
- deleted 5y ago
  [deleted]

twofornone 5y ago

The premature smear of potentially effective medications like HCQ and Ivermectin by scientifically illiterate media is unforgivable. Especially in the case of Ivermectin, given that it has one of the most benign safety profiles of any known drug. There is no excuse. There should have been federally funded widespread trials a year ago, there is no downside. Instead you now have hospitals forbidding off label prescription with threats of termination. None of it makes any sense; people are treating science as though it were a religion, and the safety and efficacy of the vaccines as some sort of core, unquestionable tenet, complete with shaming and excommunication for nonbelievers. All over a virus which has a complication rate on par with a moderate flu year.

burkaman 5y ago
There is a federally funded widespread trial, but they take a while to do correctly: https://www.nih.gov/research-training/medical-research-initiatives/activ/covid-19-therapeutics-prioritized-testing-clinical-trials#activ6 https://www.nih.gov/research-training/medical-research-initi... There was also a federally funded trial of hydroxychloroquine last year which has since concluded: https://www.nih.gov/news-events/news-releases/nih-halts-clinical-trial-hydroxychloroquine https://www.nih.gov/news-events/news-releases/nih-halts-clin...
- sjwalter 5y ago
  And in the meantime, if you buy into the crazed insanity of "pandemic! pandemic! omg we'll all die", then it makes tonnes of sense to treat people with a highly-available, incredibly safe medication that frontline clinicians all over earth are reporting success with, especially a drug that has been dosed ~4 billion times over two generations, that has been most often dosed by illiterate people and delivered by non-doctor NGO workers.
  - burkaman 5y ago
    I guess the reason doctors aren't prescribing Ivermectin is that they don't buy into "crazed insanity" and don't feel the need to try anything that might work. And I can only speak for myself, but the attitude I'm seeing is "a lot of people are dying and we should try to work together as a society to stop that from happening", not "omg we're all gonna die".

lez 5y ago

Looking at the greyed out comments it seems HN is not pro, but against scientific debate. Questioning science IS part of the scientific method. https://c19ivermectin.com/ https://c19ivermectin.com/ is a very adequate counter-argument to the article, and it's unfair to the whole scientific community that comments are greyed out that mention it.

narrator 5y ago
I think a certain segment of the population refuses to believe that there would be purposeful suppression of information that could potentially save millions. They will not believe any information that leads to that conclusion no matter what the evidence. Period. Full stop.
katbyte 5y ago
ivermectin in the end after all the bad studies were redacted had no affect: https://www.iheart.com/podcast/105-behind-the-bastards-29236323/episode/part-one-the-ivermectin-episode-86648655/ https://www.iheart.com/podcast/105-behind-the-bastards-29236...

rory 5y ago

Ivermectin probably doesn't do anything to fight Covid-19, but the American media has really shown their corruption in the way they've treated it. It's clearly a safe drug to take in human-designed doses, and it's cheap to produce. Laughing at people for poisoning themselves with "horse dewormer" instead of pointing out that they are turning to the vet store because their access to medicine has been marginalized is sick. And maybe it does help, I don't know. Unproven != disproven.

tptacek 5y ago
It matters a lot if ivermectin doesn't do anything to stop C19, even if it is otherwise safe (it surely is, dosed professionally). People take ivermectin instead of vaccinating or complying with NPIs. If ivermectin doesn't work, that is a very, very big deal.
- rory 5y ago
  > People take ivermectin instead of vaccinating or complying with NPIs Doing one thing but not another doesn't imply you're doing one thing instead of another. Do you truly believe the people ODing on ivermectin would be lining up for vaccinations if it didn't exist?
  - myrmidon 5y ago
    Lining up? Not necessarily. But it seems almost certain to me that at least some people feel safe thanks to taking ivermectin (while distrusting mainstream vaccines), and those people would turn eventually to the vaccines if those were the only perceived path towards C19 safety.
    - rory 5y ago
      Perhaps on the margin some would, but I suspect most would fall into the "natural immunity" camp. So in my mind, we need to weigh the damage done by blocking safe ivermectin use for some number of people to the damage done by a much-smaller number of people remaining unvaccinated when they otherwise would get the jab. Seems like it could go either way depending on your specific assumptions.

ashtonkem 5y ago

The other takeaway is that preprint publication is a pathway ripe for abuse. The major paper that drove most of this situation, and the meta analysis, appears to have been a straight up fraud. But it got circulated a lot as a preprint to people who didn’t understand the difference between a preprint and a peer reviewed paper. If the preprint had been more private, this might have been averted.

scoopertrooper 5y ago
What's the motivation for this sort of thing? It seems the very thing they crave (attention) will invariably bring them undone as attention invites scrutiny.
- avhon1 5y ago
  For one, money. There is an organized group that charges $90 online for hocus-pocus covid medication prescriptions [1]. The more people that can be convinced that this is a worthwhile purchase, the more money they get. https://americasfrontlinedoctors.org/treatments/how-do-i-get-covid-19-medication/ https://americasfrontlinedoctors.org/treatments/how-do-i-get...
  - ashtonkem 5y ago
    That and politics. The frontline group was also involved in the Hydroxychloroquine debacle, and they were selected specifically by political actors as a pro-trump solution to the pandemic. With any of these politically connected things, there’s always a mix of grift, political opportunism, and true believers.
sjwalter 5y ago
> The major paper that drove most of this situation, and the meta analysis, appears to have been a straight up fraud. Umm, wat?! The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians. Prior to 2020, basically everyone on earth agreed (including the WHO, who STILL agrees) that front-line clinicians and observational studies are excellent signals that can lead to scientific investigations that can lead to medical breakthroughs. The evidence for IVM as a treatment for covid (and many other viruses) is quite strong. There is, no, no large-scale RCT for IVM. However, it is inherently obvious that none will happen, none that give it a fair shake. The entire public health apparatus in the West has a huge desire to treat all illness with only on-patent, new medications. Do you not thin that this incentive influences what gets into the news? Do you think the public health authorities in Uttar Pradesh (https://indianexpress.com/article/cities/lucknow/uttar-pradesh-government-says-ivermectin-helped-to-keep-deaths-low-7311786/ https://indianexpress.com/article/cities/lucknow/uttar-prade...) are lying?

EnlightenedBro 5y ago

For those interested to learn more about Ivermectin, watch JRE#1671 podcast episode. Lots of interesting information covered about the drug by 2 biologists. It may change your views on this for the better, or the worse.

vernie 5y ago
You're better off if you only associate "JRE" with Java.
- xdennis 5y ago
  People shouldn't be taking medical advice from JRE (or celebrities (or politicians)), but what's wrong with his podcast?
veemjeem 5y ago
Dr. Pierre Kory was one of the main dudes promoting ivermectin -- he references the meta-analysis study on ivermectin that was later redacted. Of course when this interview was released (june 22), the study was not yet redacted (july 14) so it looked like the drug worked far better all the drugs including steroids & antibody treatment.

buescher 5y ago

The lesson of ivermectin: a lot of medical studies that go uncriticized because they're less controversial probably have problems similar to the problems of the retracted Elgazzar study and the other studies mentioned. Why else would these people think they would get away with it?

gwerbret 5y ago

I'm going to make what is probably a controversial statement, which is that, in my experience, most meta-analyses are trash. A meta-analysis is usually grounded on the assumption that an aggregation of multiple, well-conducted studies can provide significant information that may not be evident by taking each study individually. Essential to this assumption is the premise that those studies included in the meta-analysis be scientifically rigorous in themselves. Unfortunately, this is almost never the case. The great utility of the meta-analysis in the clinical literature is such that there have emerged a series of standards for how to conduct such analyses, such as controlling for bias, controlling for variability, etc. These seldom include actual assessment of the scientific quality of the studies, as this is harder to standardize. Consequently, there is a preponderance of meta-analyzes that come to conclusions that are simply not justified, because the studies themselves were not scientifically rigorous. I believe this applies to the situation of ivermectin, and it just so happens that this is the thrust of the point raised in the Nature article cited here.

tantalor 5y ago
FiveThirtyEight weights its averages by pollster accuracy/methodology. Next, we determine how much weight to give each poll in our average. First, polls conducted by pollsters with higher FiveThirtyEight pollster ratings — a letter grade measuring how accurate and methodologically sound pollsters are — are given more weight https://fivethirtyeight.com/features/how-were-tracking-joe-bidens-approval-rating/ https://fivethirtyeight.com/features/how-were-tracking-joe-b...
- nradov 5y ago
  There is no equivalent feedback mechanism in medical research. Other than looking for retracted papers, we don't have a reliable way to quantify whether a particular author is "correct" more often than another.
  - antman 5y ago
    The author’s Hindex could be an initial weighting factor

mechE321 5y ago

The Bayesian gambler in me wants to think this: The studies on ivermectin seem to be split between "good effect" and "no effect," and there don't seem to be any (by my extremely informal review! going off of memory here) in the camp of "bad effect." Seems reasonable to take ivermectin as a decent gamble to me while we wait on the dang science to get its head out of its butt.

simpleguitar 5y ago
If iver is a good gamble, then wouldn't the vaccine be a better gamble? After all, unlike iver, there is very good hospitalization data about vaccinated vs unvaccinated now.
- rory 5y ago
  This is true, but just because the two are on opposite sides of the culture war doesn't mean they're medically mutually exclusive.
  - simpleguitar 5y ago
    Actually, it does. The only reason one would be taking iver prophylactically, is because one wasn't vaccinated. And the only reason to take iver after covid symptoms develop is because you didn't take the vaccine. If one was vaccinated and are feeling sick enough to take iver, she would be better off with oxygen and hospital SOC.
    - rory 5y ago
      It seems like you're just saying you don't believe ivermectin works? That's fine and likely correct, but logically it's completely unrelated to its mutual exclusivity to the vaccine. For instance, if you get tetanus after having the vaccine, you'll still be given antibiotics. If someday ivermectin is proven to have a positive effect against Covid, we won't withhold it from vaccinated patients.
    - bongcloud420 5y ago

corona-research 5y ago

You shall have no other medicine besides me.

hackingforfun 5y ago

With all the criticism of the mRNA and other COVID vaccines, which actually do have science backing them up, what is the science that would make ivermectin actually work? It's an antiparasitic drug. I see a lot of criticism of the COVID vaccines, especially from the right, but then they are fine taking hydroxychloroquine or ivermectin if there is any glimmer of hope that they will work. I just don't get it. Maybe, just maybe, it's not all some big conspiracy, and the vaccines were actually designed to help people? Is that so far fetched? Doesn't taking something random like hydroxychloroquine or ivermectin seem more far fetched? It does to me.

tzs 5y ago
Here is an article from May 2020 about 15 drugs [1], including hydroxychloroquine and ivermectin, that were being looked into to see if they might help COVID. It goes into the mechanisms that led researchers to believe they were worth looking at. [1] https://www.nature.com/articles/d41591-020-00019-9 https://www.nature.com/articles/d41591-020-00019-9 Edit: Oops...forgot to link the article. Added.
- deleted 5y ago
  [deleted]
- hackingforfun 5y ago
  Interesting, thanks.
  - winocm 5y ago
    I really don't want to go back rehashing the point as to why it doesn't work, mainly because finding all of the references again and double checking the wording to make sure it matches the literature is rather time consuming... https://news.ycombinator.com/item?id=28544765 https://news.ycombinator.com/item?id=28544765
    - hackingforfun 5y ago
      I'm not saying they do work. I just appreciated the reference and thought it was interesting to read through. I am pro-vaccine and think that is the most effective course of action. Anyway, thanks for the link to your other post.

defaultprimate 5y ago

Studies are irrelevant at this point, when we have population level data of over a billion people across India and Africa, and the massive disparities between states/countries that utilized Ivermectin, and those that did not. The drug is safe enough to be used based on this data alone. https://www.thedesertreview.com/opinion/columnists/indias-ivermectin-blackout/article_e3db8f46-f942-11eb-9eea-77d5e2519364.html https://www.thedesertreview.com/opinion/columnists/indias-iv... https://www.thedesertreview.com/news/national/indias-ivermectin-blackout-part-ii/article_a0b6c378-fc78-11eb-83c0-93166952f425.html https://www.thedesertreview.com/news/national/indias-ivermec... https://www.thedesertreview.com/opinion/columnists/indias-ivermectin-blackout---part-iii-the-lesson-of-kerala/article_ccecb97e-044e-11ec-9112-2b31ae87887a.html https://www.thedesertreview.com/opinion/columnists/indias-iv... https://www.thedesertreview.com/opinion/columnists/indias-ivermectin-blackout---part-iv-keralas-vaccinated-surge/article_8a8c481c-09d3-11ec-a51c-fb063e1a3e3b.html https://www.thedesertreview.com/opinion/columnists/indias-iv... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968425/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968425/ https://journals.lww.com/americantherapeutics/fulltext/2021/06000/review_of_the_emerging_evidence_demonstrating_the.4.aspx https://journals.lww.com/americantherapeutics/fulltext/2021/...

walterbell 5y ago
At this point, news articles should include a bar chart for health interventions, including a three year projection of vendor revenue, tax costs, quality-adjusted life years, societal collateral damage, and risks based on prior usage. When one option has billions of revenue at stake, investors will pay for more/focused studies vs an option to reuse low-cost generics. Unfortunately, or fortunately, desperate humans have skipped trials of both vaccines and early treatments, so there is data on both.
NotSammyHagar 5y ago
If you are fixated on conspiracy claims against your amazing scientific discovery - pretty much you are always wrong, that's true for perpetual motion machines, faster than light drives (that's the one I hope could be right), extra-ordinary life extensions for microbes applies to humans (wish that one could be right), and covid. If you use opinion columns from obscure news sources to prove you are right, almost always wrong too. Ivermectin is safe enough to take, the important question is does it do any good against covid. At best it doesn't hurt you and it's unclear, but probably does nothing. It's certain there is no international pharmaceutical conspiracy trying to block discussion of it. That's different than trying to avoid showing incorrect medical information to people during a worldwide medical emergency. The hospitals in my state are full of idiotic non-vaxed covid victims. The latest thing is a conspiracy that the hospital won't treat them with ivermectin because they want them to die. People are just killing themselves because of their bizarre and irrational resistance to safe, life-saving vaccinations and preference for random spoutings on the internet to research proven treatments. Do people challenge their math professors in college because they don't consult fox news for the truth? No. I don't have much hope for our future when we can't get these simple things right. It's like a new dark ages has come upon us. But the truth is we humans were always this foolish.

The_rationalist 5y ago

https://ivmmeta.com/ https://ivmmeta.com/

atty 5y ago

What I find almost more interesting than the article itself is the comments that show a non-zero portion of the HN community (which I think is generally more intellectually curious and educated than average) are actually strongly arguing that ivermectin has strong effect, and even crazier, that it may be safer or more effective than the mRNA vaccines. Is this from being incapable of following science and drawing rational conclusions? Or is it more of a tribal thing, where they are exposed to a biased subset of information/misinformation, and are now emotionally invested in the success of ivermectin because their tribe is? Either way, like someone else in the comments said, these past 2 years have shown us that laypeople are incapable of following active science in real time and drawing reasoned conclusions. Frankly, this is probably true of everyone who is not an expert in the field in question. We need organizations like the CDC and FDA to be much better about their messaging (remember the no-mask debacle? Great way to lose credibility, guys and gals), and we need much better tools to shut down the spread and weaponization of misinformation from the anti-vax crowd et al. I honestly don’t have any idea of how either of those get fixed, however.

rajin444 5y ago
Your post is assuming a lot of this science is "settled". I don't think science is settled - especially in this field. Acknowledging that your own statements may be incorrect might help you down the path to figuring out a fix. Hint: as soon as you know you're right, and you make statements based on that, when you're inevitably wrong (not saying this in a disparaging way - making sense and being right through all this is nearly impossible), you will lose all trust.
- atty 5y ago
  Settled is a strong claim, but as far as I’m aware (I have many connections amongst the medical and epidemiological communities), the general consensus is that ivermectin does not work. For instance, the FDA, WHO, the AMA, the American Pharmacists Association, and the American Society of Health-System Pharmacists all say it should not be used outside of clinical trials because there is no good evidence for it, and even Merck, the manufacturer, specifically states it should not be used for COVID at all. I’m not saying no discourse or testing should happen. I’m a scientist, I believe scientific freedom, and of course, that includes a lot of disagreements. But those disagreements happen in the scientific community, not in the general public. What’s happening in the general public is not at all connected to what’s happening in the research. Instead, I’m interested in how these “treatments” with no strong evidence are getting weaponized by motivated agents (like the anti-vax crowd) to sow distrust both in scientific organizations (the CDC, and the FDA, Pfizer, Moderna, et al), and in the use of tools with proven effectiveness, like the vaccines themselves.

cyounkins 5y ago

There is a lot of confusion on whether there actually was a significant increase in calls to poison control centers due to ingestion of ivermectin. This [1] official Mississippi government document says, "At least 70% of the recent calls have been related to ingestion of livestock or animal formulations of ivermectin purchased at livestock supply centers." But then the AP [2] seemed to say that was incorrect: "The Associated Press erroneously reported based on information provided by the Mississippi Department of Health that 70% of recent calls to the Mississippi Poison Control Center were from people who had ingested ivermectin to try to treat COVID-19. State Epidemiologist Dr. Paul Byers said Wednesday the number of calls to poison control about ivermectin was about 2%. He said of the calls that were about ivermectin, 70% were by people who had ingested the veterinary version of the medicine." Does anyone have additional clarification? [1] https://msdh.ms.gov/msdhsite/_static/resources/15400.pdf https://msdh.ms.gov/msdhsite/_static/resources/15400.pdf [2] https://www.sfgate.com/news/amp/Health-Dept-Stop-taking-livestock-medicine-to-16405982.php https://www.sfgate.com/news/amp/Health-Dept-Stop-taking-live...

tedunangst 5y ago
There was an absurd rush to report that ivermectin is bad that resulted in a pretty bad breakdown of the fact checking process. A lot of semi-adjacent facts and statements got merged. A hospital is full and a hospital treated someone for overdose became all the hospitals are filled with overdose victims. (I think eating horse paste is dumb, but that doesn't excuse rolling stone lying about the consequences of doing so.)
- OrvalWintermute 5y ago
  > A lot of semi-adjacent facts and statements got merged. A hospital is full and a hospital treated someone for overdose became all the hospitals are filled with overdose victims. I thought they said gunshot victims weren't getting treated in some podunk tiny town of less than 10k residents, then they plagiarized a photo to add a racial element, using African Americans, then spread the story everywhere? https://www.msn.com/en-us/news/us/rolling-stone-covid-19-debacle-is-indicative-of-a-larger-problem-in-media/ar-AAOcqzS https://www.msn.com/en-us/news/us/rolling-stone-covid-19-deb...

mgamache 5y ago

And yet the Authors of this letter fail to address the most cited meta-analyses (by Dr Lawrie). She's publicly stated the removing the Elgazzar data did effect her numbers, but not the conclusion. Also, if you read the paper she downgrades the Niaee data for several potential biases. https://pubmed.ncbi.nlm.nih.gov/34145166/ https://pubmed.ncbi.nlm.nih.gov/34145166/

unanswered 5y ago
In this polarized world of clickbait headlines, it's never necessary to attack your opponent's strongest argument, only their weakest. (If they don't have a weakest argument you can always publish a straw man as a false flag.) Now the totally true headlines say that ivermectin studies are discredited, and it matters not one jot that the study that was discredited was already of low credibility to begin with and was never a substantial reason for believing one way or the other.

sydthrowaway 5y ago

There is no good faith argument against the vaccine. Just take it.

brigandish 5y ago
> First: the opinion which it is attempted to suppress by authority may possibly be true. Those who desire to suppress it, of course deny its truth; but they are not infallible. They have no authority to decide the question for all mankind, and exclude every other person from the means of judging. To refuse a hearing to an opinion, because they are sure that it is false, is to assume that their certainty is the same thing as absolute certainty. All silencing of discussion is an assumption of infallibility. Its condemnation may be allowed to rest on this common argument, not the worse for being common. J. S. Mill wrote the rebuttal to your argument 160+ years ago. He wasn't using it as an anti-vaxx argument either, so it might be time to stop the moralising and simply try to make a persuasive case. I'd wager it's easier without the moralising anyway.
NaturalPhallacy 5y ago
>There is no good faith argument against the vaccine. Factually false. 1. It isn't a vaccine. It's a chemical signal to make your body make things. 2. It doesn't have the efficacy against the plethora of variants that all coronaviruses like the cold continuously create. You can still get COVID-19 after being "fully vaccinated". Human beings lack the technology to vaccinate against coronaviruses, including COVID and the cold. 3. It has caused blood clots. And the proteins created cluster in reproductive organs. 4. There are no long term studies of its effects. 5. If it kills your spouse, you can't sue the manufacturer. Stop spreading misinformation about this pseudo-vaccine.
- brigandish 5y ago
  It seems that the second half of (3), and (5) are myths. https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/covid-19-vaccines-myth-versus-fact https://www.hopkinsmedicine.org/health/conditions-and-diseas...

sunkenvicar 5y ago

The vaccines become less effective over time. Just like other gene therapies which are correctly classified by the FDA as drugs. Mean age of permanent heart damage from the vaccines (DNA or RNA) is 33. No thanks. I will keep taking ivermectin prophylactically based on overwhelming anecdotal evidence from front-line doctors. We know ivermectin is safe because Merck hands it out like candy in the third world. It is 4 billion doses in 40 years safe. I accept the potential unknown risk of frequent long-term use because of the significant likely upsides. My body my choice.

pier25 5y ago

Here in Mexico most doctors are giving Ivermectin to their COVID patients.

X3h7P4icntav 5y ago

The question of whether ivermectin treats Covid19 in humans is utterly independent of vaccines, HCQ, the state of modern science, whether ivermectin treats other diseases, ivermectin's use in animals, politics, any corrupt ivermectin studies (if you ignore them), and the price of cheese on the moon. I have learned there are many idiots among us. Many, many idiots.

ivm_man 5y ago
So true...

deleted 5y ago

[deleted]