What worries me the most is that both Lowe's and the WHO's judgement were highly influenced by the Lopez study, which has a striking list of protocol violations.
Lowe mentions: "Objections have been raised to that trial’s use of an oral suspension formulation, I should note.".
But by reading the linked article we can see that there is much more to note:
"In the statistical analysis subsection of the article, the authors acknowledged 2 RCT issues: i) they modified the primary end point to time from randomization to complete resolution of symptoms within the 21-day follow-up period and ii) a labeling error occurred between September 29 and October 15, 2020, resulting in an unblinded protocol during this time frame."
Seems weird that while everyone is pushing hard on the limitations of the studies that favor IVM, we get a pass for this study by making it so influential.
Nicely written. But, as predicted in the responses on the blog the rebuttal is going to be "but I watched this video..."
The basics here are very strong for me: run larger tests (which btw, are still too small) and the numbers become at BEST equivocal. Run small tests, you can get some "stunning" evidence it works.
Stunning, because 6/10 vs 5/10 is an apparent huge leap in efficacy, when in fact, its a single flip in the margins. 6/10 is probably 5.01/10 when you do it to 100+ test subjects. 60/100 vs 40/100 would of course be more interesting, but the likelihood of 6/10 converting to 60/100 is actually low: it was most likely a single flip, not a statistical flip of a cohort. Thats what the bigger studies appear to be telling us.
"Big RCT Fundamentalism" is an interesting term. Reductionist positions are not uncommon.
A test of 20 people would very probably not have uncovered the unusual clotting problem in AZ, which is 1:100,000 order occurance. Yet, it has shaped public policy.
Tests of the order 1,000 would confirm AZ worked. Tests of the order 10,000 confirmed Pfizer and Moderna worked "better"
The PEG problem in mRNA, like the clotting problem, needs tests of the order 1m to become apparent.
If Ivermectin and HCQ had benefits, they'd be clearer if better RCT at scale were done. The benefit of steroids (for instance) were so clear, they were able to decide the protocols from thousands of tests (from what I read) which is maybe what "big RCT fundamentalism" tells us: These trials of 10 or 20 people, observational, are too strongly distorted by one and two person effects to say what the underlying trend is.
In primary school we were warned away from small sample sizes in basic stats. I'm not seeing anything here to make me think this was wrong. 100 people tell you more than 10 do, and 1000 confirms the accuracy. 1 person variance in 100 is not altering the fundamentals the way 1 person variance in 10 is.
* 0 out of 788 (0%) in the treatment group got COVID.
* 237 out of 408 (58.2%) in the control group got COVID.
The treatment group were volunteers who agreed to take it, so it wasn't an RCT.
"Big RCT Fundamentalism" discards that study, because it wasn't a big RCT, even though the signal to noise is obviously clear, and it has been replicated study after study, including smaller RCTs (when using a weekly dose of at least 0.2mg/kg).
There are no big RCTs that show the same effect, because they can cost millions and there's no incentive for anyone to fund it.
You're using a very specific complaint about science formalism not about numbers but about recruitment and randomisation. My comment went to numbers, not recruitment. If your problem is outsider science, please be more specific.
You could (for instance) cite PLOS one reports on Ivermectin instead of random domains with an axe to grind:
The ivmmeta website is a collection of public information, you can always refer to the original study/journal if you don't find it trustworthy.
It's not a lack of data. Ivermectin already has many times more data (including RCTs) compared to other WHO approved treatments (Ivermectin vs. Remdesivir, Ivermectin for COVID-19 vs Ivermectin for Scabies).
That author appears to have an axe to grind around HCQ.
He mentions - writing in August 2020 - favorably the argument that an RCT shouldn’t be performed of HCQ because it is already known to be effective. ‘ RCT fundamentalists called their [hydroxychloroquine] study “flawed” and “sloppy,” implying it had a weak methodology.’
Well, now that it’s not august 2020 and we actually have the results of well conducted HCQ RCTs, we know that HCQ turned out to be no better than snake oil. All the claimed observational improvements were just anecdotes and luck. https://www.nih.gov/news-events/news-releases/hydroxychloroq...
The mistaken conclusion that he came to around HCQ should be factored into evaluating the validity of the arguments he makes - which led him to downplay the need to study and verify whether HCQ was actually working.
There was a disinformation campaign against Hydroxychloroquine. In the failed JAMA study, they administered a nearly toxic dose at late stage patients (when there's no viral replication). This is now being investigated.
I have seen an increasing amount of Ivermectin promotion recently, and at face value it looks worth pursuing. My biggest concern is the overall shady nature of many of its proponents, and specifically when I see posts or individuals that in the same breath have a strong anti-vaccine stance that and are promoting Ivermectin. Obviously the two things have nothing to do with each other, and frankly I can't understand what the agenda is there.
Its promising to see something in Science which I hope has a higher bar, although I'm not familiar with the blogs section
Edit:
> An editorially independent blog from the publishers of Science Translational Medicine. All content is Derek’s own, and he does not in any way speak for his employer.
The emergency use authorization for the vaccines was predicated on there being no effective approved alternatives. If there's an effective approved alternative, the vaccines lose their EUA and are back to being clinical trials until full approval.
So anti-vax people want an effective treatment to be found to invalidate the EUA. Pro-vax people don't want an effective treatment to be found because it would invalidate the EUA.
Dexamethasone is a cheap generic drug that has been proven to reduce covid-19 mortality and is being used worldwide including in the USA. The studies showing that it worked occurred before the EUA for the vaccines was issued. It is officially recommended on https://www.covid19treatmentguidelines.nih.gov/therapies/imm...
I am not sure there is any actual proof that if ivermectin was shown to be, e.g., as effective as dexamethasone in reducing covid-19 mortality that it would stop the FDA from issuing a EUA for a vaccine. After all there is a big difference between a vaccine and a treatment anyway.
Ivermectin is however being promoted both as a prophylactic and a cure - https://ivmmeta.com/ (I have no idea about the reputation of this source). With big Pharmas also relying on the internet and social media to market their medicines, it has really become quite difficult to sift through bullshit and facts. Look at all the hype before with HCQ and Remdesivir last year ...
> Dexamethasone is a cheap generic drug that has been proven to reduce covid-19 mortality and is being used worldwide including in the USA. The studies showing that it worked occurred before the EUA for the vaccines was issued. It is officially recommended on [nih.gov]...
These are the same doctors that recommended the use of corticosteroids when everyone else was recommending against it.
These are the same doctors that recommended anti-coagulation treatment when everyone else was recommending against it.
These are the same doctors that identified airborne transmission of disease, the WHO is only starting to acknowledge it more than a year later.
They were ridiculed and criticised at the time for things that are now standard of care, and proved right time and time again.
They are the same doctors that are now recommending Ivermectin, and are now being censored (e.g. senate hearing removed from YouTube) and labelled as spreading medical misinformation.
This is the same technique the Motley Fool uses for their stock picking newsletters. Make lots of predictions; highlight the ones that wound up working.
All of FLCCC's work is public, and is done with no financial conflict of interest.
Dr. Pierre Kory also testified multiple times to the senate.
He published multiple studies on the matter.
If they get it right again and again it's because they follow the data, and have actual expertise in the matter.
That said, the WHO reputation is becoming more and more tarnished day by day. That's why more and more countries are starting to ignore the WHO, and with great results.
Not all vaccines are created equal. Grouping people in "pro/anti-vax" carries a risk of creating a huge backlash against vaccination in general, if the relatively new and unproven mRNA vaccines end up less than ideal. For example the virus mutates to bypass the very specific protein the vaccine targets, or there are serious side effects, possibly on the reproductive path, a few years down the pipeline. Consider being more specific, for example 'pro/anti mRNA Covid vaccines'.
Thank you for pointing this out. I've been vaccinated for many things, they're vaccines that we've had years of experience administering to people. I'm not anti-vax in any way. I'm not even anti-mRNA vaccines. What I am is cautious of new and rushed medicine rolled out at large scale. The chances of it going wrong don't have to be big, I just don't believe the risk is worth taking without more conclusive research. I'd have the same worries if WHO recommended everyone start taking IVM weekly for the duration of the pandemic (if I'm not mistaken almost all research on IVM has focused on short-term usage).
Politicians talking about "getting everyone medicated (or vaccinated) as soon as possible" with anything that doesn't have long-term studies should be worrying to all. And the fact that some SV companies will not allow this discourse to happen should be even more so.
Why do you assume that „pro-vax people“ would not want to see an effective treatment?
They are „pro-vax“ because it prevents harm to them and others. Effective treatment helps with that.
People are pro-vax because they want this pandemic to end! The majority of Americans have taken it and it's safe, I have taken it and feel happy knowing I won't have to worry about getting long covid. Anti-vax people are only extending this pandemic and fail at the most basic reasoning. I mean I can understand people being hesitant when the vaccines were first authorized, but now that most Americans have taken it, the idea someone would still risk COVID over getting vaccinated is insane.
Wanna know what does have high risk for long term side effects? COVID.
I find it rather troubling, lumping scepticism of these experimental, emergency authorized vaccines in the same category as existing vaccines that have had decades of use and well known safety profiles . It puts you into "yes" or "no "camps, without acknowledging potential unknown problems with these rushed vaccines. There are no long term studies.
I am not anti-vaccine, but I don't think we should be as gung-ho as we are with these vaccines, especially on young people who are at very low risk from covid. Vaccinating children seems immoral.
> a strong anti-vaccine stance that and are promoting Ivermectin. Obviously the two things have nothing to do with each other, and frankly I can't understand what the agenda is there.
One of the people I know is one of these people. Pro Ivermectin and anti vaccine.
It’s tied together by their belief that COVID was overblown, an attempt by the government to seize control, or an attempt by big pharma to make piles selling COVID vaccine. Or all three.
Basically to this person, Ivermectin being a cure is proof that the government/doctors/pharma manufactured the crisis.
What connects antivax and untutored Ivermectin promotion is a generalized, reflexive, contrarian rejection of anything perceived as "establishment" science.
For some it’s also an application of the precautionary principle, and a worry that rushing into widespread application of an experimental treatment may present unknown harms. Contra to the contrarians rejecting establishment science, a secondary concern driving the precautionary perspective is a fear that if there are major medium or long term complications then it would lead to a widespread distrust of the scientific establishment itself.
The problem is that an epistemic closure around this issue has emerged for a variety of reasons, so the people who are skeptical and willing to talk about it are few in number and looking for allies, so you end up with a rather motley crew.
I’m interested in what people like Pierre Kory and Tess Lawrie say on this issue because they seem like credible people without a track record of crankery, and they’ve looked at the same evidence as the WHO and come to different conclusions. Even if they are wrong it is interesting to engrave with and figure out why. And if they are right, it would be good to figure that out sooner rather than later. But any time I stick around in the forums where their work is discussed the comments section is often overrun by unhinged wackos with different motivations.
The thing that really defeats the ivermectin argument is simply effect size (or, equivalently, drug effectiveness). For a drug to be useful, it needs to have a larger effect than existing therapies. The larger the effect, the more useful. And the larger the effect, the easier it will show up in studies.
Ivermectin's trial results are mediocre at best. So it can't be that powerful a treatment. It's probably helping a bit, or at least not hurting, but it's not a wonder drug. We'd have seen that if it were!
So then you get into the usual lines of bullshit, as we saw before with the hydroxychloroquine people. "Augment with unicorn horn dust" and "dose more" and "dose earlier" and all that. But COVID-19 is the sort of disease that is impractical to dose too early, so "must dose very early" just means "drug is useless".
Thus the facts are clear: even if ivermectin works, it isn't useful. It was a great hypothesis to test. It failed in the clinic. So it's irresponsible to continue beating against it when we have better avenues to pursue.
Yes, its safety profile and production are well-established.
But as far as covid is concerned, it is some random drug. Metformin is also a wonder drug, should we bet our lives on it for covid? No? You say there are more useful things?
I really don't understand why people think this drug can work. It was trialled. It neither passed with flying colors nor flamed out. That's... pretty much what most drug candidates do. It doesn't really "remain to be seen" here: there's plenty of evidence for "doesn't move the needle".
The fact that is it’s effective at early stages does not make it useless. It could be taken prophylacticaly if you know you’re going to be in a high risk situation like a roommate tests positive.
...or you can get vaccinated first? Or actually quarantine (alone)? And I do hope you were lucky enough to stockpile it beforehand, because you'd better not be going out too often with such a test result....
It could have some covid uses, sure. But it can't change the game. Hence my label of "useless" in overall pandemic management (much like contact tracing). I admit that "almost useless" or "only useful in very niche situations" is more accurate. But it is useless 99.9% of the time.
Although the CDC has decided to stop counting them, breakthrough infections and even death are common among the vaccinated. There's not going to be a point where we don't need to worry about treatment unless the virus is going to go away like the Spanish flu once enough people are immune.
> And I do hope you were lucky enough to stockpile it beforehand, because you'd better not be going out too often with such a test result....
It's pretty clear from this that you have never looked into how ivermectin was used in certain Indian states or in Chiapas, where local officials readied pre-made kits which could be distributed to high risk people and those who tested positive. This would be easy enough to do in the US if we could shift the thinking on Covid away from "you have to wait until you're gasping for breath at the hospital to start any treatment other than acetaminophen."
Do you feel similarly about lockdowns being "useless" given their demonstrated inability to fully eliminate spread of the virus, and the lack of any large RCTs in support of them? I mean, I see all the same arguments made in their favor: "you have to do them early enough, you have to pair them with such-and-such other NPIs, etc"
Talking about a prophylactic use case might have made sense a year ago but makes zero sense today, when more than 50% of the adult population is vaccinated and 70-80% of many states are vaccinated while most are fully reopened without capacity limits or mask mandates.
What are we doing here? Is this really the hill they want to die on?
> It's promising to see something in Science which I hope has a higher bar, although I'm not familiar with the blogs section.
I'm a regular reader of this blog. I have an specialization in Chemistry in the Secondary School, so I can vouch that his articles about Chemistry are solid (and adobe my knowledge level). I'm convinced that the articles about the pharmaceutical industry are correct, but that's a little more far away from my specialization.
About Ivermectin, someone posted a few days ago a site that collect all the favorable evidence. I read a few of the papers and in my opinion it's not convincing. The papers are studies with a small number of persons, or with a small difference or instead of the control group they compare with dubious numbers. Essentially, the same conclusion of this blog post, but I only skimmed a few papers and he probably read most of them carefully. If I were you, I'd thrust his opinions more than mine, but in this case we agree.
> have an specialization in Chemistry in the Secondary School
Not familiar with American idioms. What does this mean? Secondary School is what you go to after Primary School where I come from, but clearly you can’t mean that.
I think the OP is Brazilian (submissions include links to blog), in which case Secondary extends to 18, so equivalent to A-level in the UK for example.
Almost. I'm from Argentina. I'm not sure about the translation, and the system has changed recently, so the current information may be different.
My "Secondary School" was from 13 to 18 (6 years). https://es.wikipedia.org/wiki/Educaci%C3%B3n_Secundaria_T%C3... You had one additional year than a normal "Secondary School" here, it [1] includes normal classes in the morning but less History/Geography/Whatever and in my case more Chemistry, a lot of Chemistry. Half of the days in the afternoon we had practical classes, making Chemistry experiments. At the end, I get a the "Secondary School" degree that enables me to go to the university and also some official habilitation to run a small chemistry factory or laboratory (oversimplifying the legal details) (probably is more accurate to say that I can supervise a few persosns in a factory or a lab).
Other students instead of Chemistry classes had Masonry classes and got an habilitation to build a small house (up to 2 stories?) and other Electronic classes, ... Each School has a different specialization, a bunch of specializations.
Edit: [1] The last 4 years. And the first 2 years have also more technical classes than a usual school, but they mix other stuff like basic electricity or metalworking.
Thanks for the correction -- I think the confusion comes from "secondary" which is 11-16 in the UK, so "secondary chemistry" is fairly basic (I have it, and I know nothing of chemistry)
> a strong anti-vaccine stance that and are promoting Ivermectin
I would assume that the core of this sentiment is something like “vaccine is a semi-permanent modification of immune response while ivermectin is a temporary chemical adjustment”
Obviously the two things have nothing to do with each other, and frankly I can't understand what the agenda is there.
The apparently-rational argument the shady-type make that Ivermectin is so good you don't need vaccines. But I don't think any honest advocates can claim that.
The fuzzy-irrational argument is you can't "trust" the medical industrial complex 'cause they're pushing vaccines and suppressing Ivermectin.
This stuff is terrible but there's method to their madness.
If someone's interested in learning about the evidence for Ivermectin, I've written a summary of the main notes from the Ivermectin Global Summit.
This is a good introduction to the overwhelming wealth of data showing that Ivermectin is a safe and effective in the prevention and early treatment of COVID-19.
Unfortunately, by managing trials such that no early treatment takes place and the experimental medicine in quesiton isn't administered until the virus is entrenched, they not only dishonestly "proved" that ivermectin and hcq don't work, but they created test conditions where they could prove that _nothing_ works.
The emergence of virulent variants that the existing vaccines don’t work against, especially in countries that are already behind on vaccinations or unable to acquire vaccines is a good reason to not stop research into treatments that may provide other options.
I’m not making a claim that ivermectin is that treatment, but saying “who cares” goes against the old advice that “if you have one you have none, and if you have two you have one.” It’s always good to have options.
Yes, but long-covid symptoms (no smell, heart muscle, nerves) are troublesome, so you better do something against it. same as with a bad flu. you need to help fighting the side-effects of the viral infections, and then the bacterial infection caused by the viral infections.
Less than 10 weeks ago the UN agency responsible for international health convened "an independent, international panel of experts, which includes clinical care experts in multiple specialties and also include an ethicist and patient-partners." Their findings concluded there was in fact "very low certainty" of any possible positive effects.
The group reviewed pooled data from 16 randomized controlled trials (total enrolled 2407), including both inpatients and outpatients with COVID-19. They determined that the evidence on whether ivermectin reduces mortality, need for mechanical ventilation, need for hospital admission and time to clinical improvement in COVID-19 patients is of “very low certainty,” due to the small sizes and methodological limitations of available trial data, including small number of events.
Ivermectin is great against many parasitic worms, and it's probably not going to kill your collie anymore (those lines died off a decade and more ago).
Many ivermectin proponents online also advocate against the vaccine.
If someone does accept the validity of the scientific studies of vaccine effectiveness, they probably aren’t so jazzed about promoting ivermectin because they’d realize vaccines are even more effective and a permanent or semi permanent solution, rather than having everyone in the country have to regularly take a new medication.
In any case ivermectin appears to be the new hydroxychloquine. A medicine that was randomly seized on as theoretically being effective against viruses and has failed in every properly conducted RCT.
Therapeutic efforts would be far better focused on making mAb treatments cheaper and more available, since they’ve been proven about 80% effective both as prophylaxis and a therapeutic.
> In any case ivermectin appears to be the new hydroxychloquine. A medicine that was randomly seized on as theoretically being effective against viruses and has failed in every properly conducted RCT.
Vaccines are part of the solution, but they are not a panacea.
Not everyone is willing to take them and there aren't enough of them to vaccinate the entire world.
If the disease is still raging in any part of the world, that will lead to variants which will eventually escape the vaccine, thus restarting the cycle again.
As far as I know it’s a subject of some debate whether full immune escape from the mRNA vaccines is probable even given new variants. The spike protein can only be reconfigured in so many ways, it’s not like the flu.
Only a small percent of the world is vaccinated with mRNA vaccines, thus it's not a global solution.
Some vaccines are already ineffective with the variants, e.g. Chile has one of the highest vaccination rates in the world, but doesn't have the disease under control.
There are different ways to get COVID under control:
* Vaccination
* Get naturally infected - natural infection offers broad and long lasting immunity
* Prophylaxis
* Early treatment
The data is showing that Ivermectin is almost 100% effective as a prophylaxis, and that early treatment on first symptoms, it's on par with a flu.
Currently we're only pursuing vaccination as the only solution, resulting in millions of unnecessary deaths and trillions of economic damage.
Some people are hesitant to use a vaccine without long term safety data, and using Ivermectin is a safe alternative that also contributes to herd immunity.
> Get naturally infected - natural infection offers broad and long lasting immunity
Baffling to see this listed as a way to get covid “under control”. If people getting naturally infected is fine, what is there to control? The whole reason people are concerned about getting covid under control is that natural infection would kill around 0.5% of a population in a developed country, or more if the hospital system becomes overwhelmed and oxygen or other standard of care treatment isn’t available.
> The data is showing that Ivermectin is almost 100% effective as a prophylaxis
No placebo controlled RCT has shown this that I’m aware of for ivermectin (as discussed in the parent article). The evidence for the vaccines, steriod, or mAb treatments working is backed by placebo controlled RCT. The article states: “ All in all, though, the most compelling reports of ivermectin’s effects seem to come from the smallest and least controlled samples (all the way down to anecdotal results) while the larger and more well-controlled trials tend to produce equivocal evidence at best.”
> and using Ivermectin is a safe alternative that also contributes to herd immunity.
How would it create herd immunity? Would people have to take ivermectin for the rest of their lives as an alternative to the vaccine?
> The whole reason people are concerned about getting covid under control is that natural infection would kill around 0.5% of a population in a developed country
This number is way, way off. It's not even close to the actual number of officially tallied deaths divided by confirmed cases so far, which would itself overstate the real IFR for a number of reasons.
> or more if the hospital system becomes overwhelmed and oxygen or other standard of care treatment isn’t available.
To the extent this is even a real phenomenon, it correlates better with places which have underfunded and straining hospital systems as opposed to those which eschew lockdowns and other NPIs.
> It's not even close to the actual number of officially tallied deaths divided by confirmed cases so far
It's much lower than the number of officially tallied deaths divided by confirmed cases so far. That number is around 1.8% in the USA. If you divide officially tallied deaths by the CDC's best estimate of total infections, including unreported and asymptomatic cases, you get an IFR of 0.52%.
> How would it create herd immunity? Would people have to take ivermectin for the rest of their lives as an alternative to the vaccine?
Let's say you need 75% for herd immunity. If you have 25% vaccinated, 25% who have already got the infection, and 25% who are taking Ivermectin once a week, you've reached herd immunity. When the R0 is below 1, it will exponentially reduce infections towards zero within months.
With effective early treatments, it doesn't even matter how many people get infected as long as they don't get severely ill.
> Nobody in their right minds thinks that this is the ideal way to get it under control, but it's one of the ways that can contribute to herd immunity.
Anyone can check the comments in the article, or here https://osf.io/u7ewz/
Lowe mentions: "Objections have been raised to that trial’s use of an oral suspension formulation, I should note.". But by reading the linked article we can see that there is much more to note:
"In the statistical analysis subsection of the article, the authors acknowledged 2 RCT issues: i) they modified the primary end point to time from randomization to complete resolution of symptoms within the 21-day follow-up period and ii) a labeling error occurred between September 29 and October 15, 2020, resulting in an unblinded protocol during this time frame."
Seems weird that while everyone is pushing hard on the limitations of the studies that favor IVM, we get a pass for this study by making it so influential.