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

nature.com

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

#61

Post by scoopertrooper »

nradov wrote: post #31
Spellman wrote: post #10

Earlier quoted context omitted.

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-figur... Also, the Nature article is conce…

Sure that's a good point. But is mortality the appropriate clinical trial endpoint? Mortality rates are already low when following the NIH treatment guidelines, so it would take a large study population to discern any statistically significant effects. https://www.covid19treatmentguidelines.nih.gov/ In addition to mortality it probably makes sense to look at other endpoints such as patient reported symptoms, RT PCR t…

Case fatality has been declining for sure, but it's still at about 3%. So it shouldn't be that hard to find a signal.

https://www.abs.gov.au/articles/covid-19-mortality-0

https://www.ajtmh.org/view/journals/tpmd/104/6/article-p2176...

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

#62

Post by Gimpei »

motoboi wrote: post #32

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

Society isn't ready to watch science any other way either. Media outlets routinely take individual studies and vastly inflate their results. I suppose it's better if the study is peer reviewed, but not much.

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

#63

Post by shrubble »

rory wrote: post #25

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 s…

Incidentally, approximately 11 to 14% of the USA population has pinworms, which can be easily stopped by ivermectin. Given the very high level of safety of ivermectin, it might make sense to make it easier to get on this basis alone.

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

#64

Post by buescher »

gorwell wrote: post #11
dekhn wrote: post #4

Earlier quoted context omitted.

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).

How useful is meta analysis if half or more of the experiments don't replicate? As we increasingly discover with the replication crisis.

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?

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

#65

Post by koboll »

sjwalter wrote: post #56
mlyle wrote: post #49

Earlier quoted context omitted.

> The vast majority of the studies about Ivermectin have been observational, run by front-line clinicians. OK, so weak evidence. > 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. Sure-- weak/crappy evidence and practitione…

Calling the investigatory and experiential evidence of thousands of highly-trained doctors (some of whom pioneered the standard of care for covid) as "weak evidence" is something that only somebody carrying water for large pharmaceutical companies would say. Doctors in my area are prescribing IVM to treat covid because in their experience and that of their peers IT WORKS. They have fewer deaths, fewer complications.…

It's weak evidence because COVID-19 observational studies are riddled with confounders due to COVID patients generally throwing everything at it they can to try and stay alive.

The exact same pattern occurred with hydroxychloroquine. Lots of small observational studies showed promise. Then it repeatedly failed large RCTs. It turns out that the people with the resources to use HCQ also had the resources to use other things, things that were actually effective.

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

#66

Post by danaris »

sjwalter wrote: post #50
burkaman wrote: post #43

Earlier quoted context omitted.

There is a federally funded widespread trial, but they take a while to do correctly: 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-clin...

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-do…

Penicillin is also a highly-available, incredibly safe medication that's been given billions of times.

It still doesn't make any sense to try giving it to COVID patients, because there's no reasonable way it would actually help them.

Just because a particular medication is unlikely to kill you doesn't mean it's a good idea to promote its use against a particular threat, when that threat is completely unrelated to what the medication actually does. Penicillin is an antibacterial. Ivermectin is an antiparasitic. Neither of these are likely to be helpful against a virus.

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

#67

Post by input_sh »

shadowgovt wrote: post #36
rory wrote: post #25

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 s…

How many users have been taking it in human-designed doses, given that it's not generally prescribed for COVID-19 (and therefore those who are taking it for that purpose are mostly self-medicating)?

There's a right-wing group prescribing it: https://en.m.wikipedia.org/wiki/America%27s_Frontline_Doctor...

They're also the ones that pushed Hydroxychloroquine, have connections to the Tea Party, that "demon semen" lady Trump endorsed is associated with them, and they had their leader and their chief of communication arrested due to their participation in Jan 6th.

They're also the reason you'll see Joe Rogan now spreading ivermectin bullshit.

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

#68

Post by dionian »

_2d30 wrote: post #27
gonational wrote: post #9

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 decisio…

> 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.

Well, there are certainly no long-term studies.

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

#69

Post by dataduck »

greenonions wrote: post #39
motoboi wrote: post #32

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

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.

Perhaps, but unfortunately #1 is more realistic.

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

#70

Post by tehjoker »

sjwalter wrote: post #45
ashtonkem wrote: post #26

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.

> 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 scient…

"Antiviral Effects of Ivermectin in COVID-19- Clinically Plausible?"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225296/

"In a study demonstrating the in vitro antiviral activity of ivermectin, upon incubation of infected Vero/hSLAM cells with 5 μM ivermectin, there was an approximately 5000-fold reduction of viral RNA by 48 hours in ivermectin treated samples as compared with control. The IC50 of ivermectin was found to be approximately 2.5 μM. Ivermectin seems to act on IMPα/β1 and inhibits the nuclear translocation of SARS-CoV-2 (Caly L et al., 2020). Further in-silico studies are required to confirm this target of ivermectin in SARS-CoV-2. The concentrations of 2.5 and 5 μM correspond to plasma concentrations of 2190 and 4370 ng/mL, respectively. These concentrations are 50–100 times the peak plasma concentration achieved with the 200 μg/kg of ivermectin (the US Food and Drug Administration recommended dose for treatment of onchocerciasis) (Chaccour C et al., 2017). Even with a dose 10 times greater than this dose (i.e., 2000 μg/kg), a peak plasma concentration of only ~250 ng/mL has been achieved (Guzzo CA et al., 2017)."

"On the basis of the rationale above, any significant antiviral activity could not have been achieved with the dose used in the study and the resultant plasma concentration of the administered ivermectin. Thus, although ivermectin, in vitro, is a potent inhibitor of SARS-CoV-2 replication, in vivo, the plasma concentration required to achieve the antiviral effect far exceeds the therapeutically applicable dose."

This thread discusses why the example of Uttar Pradesh's program isn't good evidence.

https://twitter.com/GidMK/status/1440131176665006088

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