Ivermectin

Covid-19 discussion, bring your own statistics
Chris Preston
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Re: Ivermectin

Post by Chris Preston » Wed Sep 08, 2021 10:14 am

Ivermectin poison control calls triple in Washington.

Not all are reports of poisoning, but a number of people have been hospitalised.
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tom p
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Re: Ivermectin

Post by tom p » Wed Sep 08, 2021 10:24 am

basementer wrote:
Tue Sep 07, 2021 5:13 pm
Al Capone Junior wrote:
Tue Sep 07, 2021 4:22 pm
Beau of the 5th column, a very cool commentator on American society, weighs in on ivermectin

https://m.youtube.com/watch?v=dByVMsE08FA
That's a good level-headed commentary. I'd not heard of him before.

yeah, he's really good

Chris Preston
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Re: Ivermectin

Post by Chris Preston » Wed Sep 08, 2021 10:27 am

Why vaccine skeptics are all in on ivermectin

Quite a nice discussion of the thinking. Also explains why it is so hard to change the thinking.

"Rogue remedies like ivermectin and hydroxychloroquine are most popular among people who are skeptical of vaccines and other treatments – precisely because those treatments haven’t gone through the same process of scientific and expert review that they distrust. For people who are suspicious of mainstream scientific thought, information that appears to come from other sources often seems independent, insightful and brave. These skeptics insist that they can evaluate health information themselves, and contested claims from nonofficial sources let them feel like they’re doing so, which can paradoxically make those claims seem truer and therefore more appealing than the mainstream ones."
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Chris Preston
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Re: Ivermectin

Post by Chris Preston » Fri Sep 10, 2021 9:59 am

Australian regulator bans ivermectin prescriptions for COVID-19.

That will upset the anti-vaxxers even more.
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sTeamTraen
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Re: Ivermectin

Post by sTeamTraen » Fri Sep 10, 2021 8:08 pm

Accepted today for publication in Nature Medicine:

The lesson of Ivermectin: Meta-analyses based on summary data alone are inherently unreliable.

Jack M Lawrence1, Gideon Meyerowitz-Katz2, James A J Heathers3, Nicholas J L Brown4, Kyle A Sheldrick5

1 St George’s, University of London, London, United Kingdom
2 School of Health and Society, University of Wollongong
3 Cipher Skin, Denver CO, USA
4 Linnaeus University, Växjö, Sweden
5 University of New South Wales, Kensington, Australia

To the Editor - The global demand for prophylactic and treatment options for COVID-19 has in turn created a demand for both randomised clinical trials, and the synthesis of those trials into meta-analyses through systematic review. This process has been fraught, and has demonstrated the risks inherent in current approaches and accepted standards of quantitative evidence synthesis when dealing with high volumes of recent, often unpublished trial data of variable quality.
Research into the use of Ivermectin (a drug which has an established safety and efficacy record in many parasitic diseases) for COVID-19 treatment and/or prophylaxis has illustrated this problem well. Recently, we described flaws in one randomised control trial of Ivermectin (1), the results of which represented more than 10% of the overall effect in at least two major meta-analyses (2,3). We described multiple irregularities in the data that could not be consistent with them being experimentally derived. (4) That study has now been withdrawn by the preprint server (5) on which it was hosted.
We also raised concerns about unexpected stratification across baseline variables in another randomised controlled trial for Ivermectin(6), which were highly suggestive of randomisation failure. On 18 July 2021 we wrote to the authors of this article, which was then only a preprint to request their data. However, as of 9 September 2021 we have still not received a response, even though the article has been peer-reviewed and published in the meantime.
The authors of one recently published meta-analysis of ivermectin for COVID-19 (2) have publicly stated that they will now reanalyse and republish their now-retracted meta-analysis and will no longer include either of the two papers just mentioned. As (1) and (6) were the only studies included in that meta-analysis to demonstrate an independently significant reduction in mortality, the revision will likely show no mortality benefit for ivermectin.
Several other studies claiming a clinical benefit for ivermectin are similarly fraught, and contain impossible numbers in their results, unexplainable mismatches between trial registry updates and published patient demographics, purported timelines that are not consistent with the veracity of the data collection, and substantial methodological weaknesses. We expect further studies supporting ivermectin to be withdrawn over the coming months.
Since the above primary studies were published, many hundreds of thousands of patients (7) have been dosed with Ivermectin, relying on an evidence base that has since substantially evaporated under close scrutiny.
Relying on low quality or questionable studies in the current global climate presents severe and immediate harms. The enormous impact of COVID-19 and the consequent urgent need to demonstrate the clinical efficacy of new therapeutic options provides fertile ground for even poorly-evidenced claims of efficacy to be amplified, both in the scientific literature and on social media. This context can lead to the rapid translation of almost any apparently favourable conclusion from a relatively weak trial or set of trials into widespread clinical practice and public policy.
We believe that this situation requires immediate remediation. The most salient change required is a change in perspective on the part of both primary researchers and those who bring together the results of individual studies to draw wider conclusions. Specifically, we propose that clinical research should be seen as a contribution of data towards a larger omnibus question rather than an assemblage of summary statistics. Most, if not all, of the flaws described above would have been immediately detected if meta-analyses were performed on an individual patient data (IPD) basis. In particular, extreme terminal digit bias, duplication of blocks of patient records, and other irregularities would have been both obvious and immediately interrogable from raw data if provided.
We recommend that meta-analysts studying interventions for COVID-19 should request and personally review individual patient data in all cases, even if IPD synthesis techniques are not used. In a similar vein, all clinical trials published on COVID-19 should immediately follow best-practice guidelines and upload anonymized IPD so that this type of analysis can occur. Any study for which authors are not able or not willing to provide suitably anonymised IPD should be considered at high risk of bias for incomplete reporting and/or excluded entirely from meta-syntheses.
Hurdles to the release of individual patient data from clinical trials are well described, and generally addressable with careful anonymisation and integration of data sharing plans at the ethical approval stage of trial planning.
We recognise that this is a change to long accepted practice and is substantially more rigorous than the standards that are typically currently applied, but we believe that what has happened in the case of ivermectin justifies our proposal: a poorly-scrutinised evidence base supported the administration of millions of doses of a potentially ineffective drug globally, and yet when this evidence was subjected to a very basic numerical scrutiny it collapsed in a matter of weeks. This research has created undue confidence in the use of ivermectin as a prophylactic or treatment for COVID-19, has usurped other research agendas, and likely resulted in inappropriate treatment or substandard care of patients.
We recognise that by recommending individual patient data review by default for meta-analysis of potential therapeutics in COVID-19 we are calling for change to nearly universally accepted practice over many decades, but the consequent potential for patient harm on a global scale demands nothing less.

Citations:
1. Ahmed Elgazzar, Abdelaziz Eltaweel, Shaimaa Abo Youssef et al. 28 December 2020, PREPRINT (Version 3) available at Research Square [https://doi.org/10.21203/rs.3.rs-100956/v3]
2. Bryant, A. et al. , (2021). American journal of therapeutics, 28(4), e434–e460. https://doi.org/10.1097/MJT.0000000000001402
3. Hill A et alOpen Forum Infectious Diseases, 2021;, ofab358, https://doi.org/10.1093/ofid/ofab358
4. Davey, M. The Guardian, July 16 2021, https://www.theguardian.com/science/202 ... l-concerns
5. Elgazzar A et al. Res Square. 2020. doi: 10.21203/rs.3.rs-100956/v2.Preprint
6. Shakhsi Niaee M et al. Asian Pac J Trop Med 2021;14:266-73
7. Mega, ER Nature (2020): 481-482.
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Chris Preston
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Re: Ivermectin

Post by Chris Preston » Fri Sep 10, 2021 9:59 pm

Did you think about recommending that authors with axes to grind shouldn't get involved in meta analyses? Bryant et al. also tended to assess the more positive studies as being more reliable than they clearly were. Even before it was known they were fraudulent.
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sTeamTraen
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Re: Ivermectin

Post by sTeamTraen » Fri Sep 10, 2021 10:15 pm

Chris Preston wrote:
Fri Sep 10, 2021 9:59 pm
Did you think about recommending that authors with axes to grind shouldn't get involved in meta analyses? Bryant et al. also tended to assess the more positive studies as being more reliable than they clearly were. Even before it was known they were fraudulent.
I would hope that's kind of a given, via things like CoI statements and/or peer review. Our letter is more about saying that the basic standards for an MA should include having access to the original data rather than the summary statistics. We're finding fraudulent or completely f.cked papers on Ivermectin (and, in a case I'm working on, another repurposed antiparasitic, nitazoxanide) one after another, many of which are in MAs totally distorting the numbers.

On the plus side, Andrew Hill seems to have pivoted from "the evidence for IVM is impressive" to "er, it seems like the evidence for IVM is shite". (That is getting the kind of reception you would expect from Frootloop Twitter.) Hopefully our little Gang of Five won't be the only people publicly calling out the fake stuff soon. (Apart from anything else we're in 4 time zones and only all out of bed at the same time for about an hour a day.
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tom p
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Re: Ivermectin

Post by tom p » Thu Sep 16, 2021 10:20 am

That's an excellent letter and I completely agree with your proposals

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Woodchopper
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Re: Ivermectin

Post by Woodchopper » Thu Sep 16, 2021 11:38 am

Yes, well done.

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jimbob
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Re: Ivermectin

Post by jimbob » Thu Sep 16, 2021 12:38 pm

I cannot find now, but maybe someone else knows. There was a good article/thread (?) explaining how Ivermectin came to be seen as a bit of a cure-all (in Brazil?) after its success against parasites.
Have you considered stupidity as an explanation

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sTeamTraen
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Re: Ivermectin

Post by sTeamTraen » Thu Sep 16, 2021 8:42 pm

The BBC is taking on ivermectin. First Ros Atkins came up with this gem. I also cannot confirm or deny whether you will be seeing more stuff about the fake research aspect of the story on the BBC website and perhaps elsewhere over the next few days.
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sTeamTraen
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Re: Ivermectin

Post by sTeamTraen » Fri Sep 17, 2021 2:55 pm

An unequivocal anti-ivermectin piece in Business Insider, in which I get to show off my extensive knowledge of medicine and pharmacology. (It is antibiotics for bacterial infections, right? :lol:)
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Martin Y
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Re: Ivermectin

Post by Martin Y » Fri Sep 17, 2021 3:13 pm

sTeamTraen wrote:
Thu Sep 16, 2021 8:42 pm
The BBC is taking on ivermectin. First Ros Atkins came up with this gem.
That was fun.
I also cannot confirm or deny whether you will be seeing more stuff about the fake research aspect of the story on the BBC website and perhaps elsewhere over the next few days.
I can neither confirm nor deny that I'm looking forward to it.

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