Comment by gjsman-1000 | Hacker News Reader

Comment by gjsman-1000 | Hacker News Reader

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Not to defend Ivermectin use, but your BMJ link advises against Ivermectin due to a lack of evidence one way or the other and the current analysis methods may be misleading either way, not because there is actual evidence of failure.

"These websites show pooled estimates suggesting significant benefits with ivermectin, which has resulted in confusion for clinicians, patients and even decision-makers. This is usually a problem when performing meta-analyses which are not based in rigorous systematic reviews, often leading to spread spurious or fallacious findings. Concluding, research related to ivermectin in COVID-19 has serious methodological limitations resulting in very low certainty of the evidence, and continues to grow. The use of ivermectin, among others repurposed drugs for prophylaxis or treatment for COVID-19, should be done based on trustable evidence, without conflicts of interest, with proven safety and efficacy in patient-consented, ethically approved, randomised clinical trials."

The obvious solution is to prescribe every medication when there's no evidence for or against it. Just take every medication that hasn't been proven not to work, and you'll be cured! Oh, wait...

I think this is straw-manning the argument.

Imagine it's 2020. There's no vaccine, you are immunocompromised, you caught COVID, and now you are dying.

If I'm dying, is it unethical for me to, with informed consent, try whatever drug I am interested in, regardless of origin, to save my life? Even if there is not evidence for or against such a drug? At that point, I don't care if it's mixing herbs grown on the seventh peak of the Himalayas, I think I should have the right to try whatever I damn well please. Even if Ivermectin is useless, at least my family won't get wrapped up in conspiracy theories that I was denied lifesaving treatment for political reasons.

Obviously, this is different than for people who have COVID and are not dying, but we used to emphasize personal responsibility for stupidity.

The thing is it isn’t 2020 and we have a lot more data to work with.

Also, medications both useful and not cause harm. Thus the default is to not use them unless there is some reason to believe they are actually useful or you’re conducting research. Yolo it is just a really really bad idea.

> Thus the default is to not use them unless there is some reason to believe they are actually useful or you’re conducting research. Yolo it is just a really really bad idea.

There actually was such a reason to believe:

2021, The Lancet: "Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial"[0]:

"[A] significant difference was found in patients with higher median plasma IVM levels (72% IQR 59–77) versus untreated controls (42% IQR 31–73) (p = 0·004)."

2021, The Japanese Journal of Antibiotics: "Global trends in clinical studies of ivermectin" (authored by 4 doctors, including Satoshi Ōmura, winner of the Nobel Prize in 2015 for his work on ivermectin)[1]:

"As of the 27th of February 2021, the results of 42 clinical studies worldwide have undergone meta-analysis and concluded that ivermectin is effective in the treatment and prevention of COVID-19. In the UK, a consensus-based recommendation by 75 healthcare professionals from 17 countries around the world has been carried out and submitted to the WHO to further encourage the issuance of guidelines for the use of ivermectin in the treatment and prevention of COVID-19."

2017, The Journal of Antibiotics: "Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations"[2]:

"Recent research has confounded the belief, held for most of the past 40 years, that ivermectin was devoid of any antiviral characteristics. Ivermectin has been found to potently inhibit replication of the yellow fever virus, with EC50 values in the sub-nanomolar range. It also inhibits replication in several other flaviviruses, including dengue, Japanese encephalitis and tick-borne encephalitis, probably by targeting non-structural 3 helicase activity. Ivermectin inhibits dengue viruses and interrupts virus replication, bestowing protection against infection with all distinct virus serotypes, and has unexplored potential as a dengue antiviral. Ivermectin has also been demonstrated to be a potent broad-spectrum specific inhibitor of importin α/β-mediated nuclear transport and demonstrates antiviral activity against several RNA viruses by blocking the nuclear trafficking of viral proteins. It has been shown to have potent antiviral action against HIV-1 and dengue viruses, both of which are dependent on the importin protein superfamily for several key cellular processes. Ivermectin may be of import in disrupting HIV-1 integrase in HIV-1 as well as NS-5 (non-structural protein 5) polymerase in dengue viruses."

[0] https://www.thelancet.com/journals/eclinm/article/PIIS2589-5...

[1] https://web.archive.org/web/20210325035449/http://jja-conten...

[2] https://www.nature.com/articles/ja201711

There where several reviews mislead because: “ The hype around ivermectin is driven by some studies where the effect size for ivermectin is frankly not credible, and this has driven the conclusions in other reviews. The study with a huge effect has now been retracted as fake. Careful appraisal is the cornerstone of Cochrane’s work, and with such extreme public demands for a drug to work during the pandemic, it remains vital that we hold onto our scientific principles to guide care.” https://cidg.cochrane.org/news/new-cochrane-review-ivermecti...

Looking at those same 41 trials: https://pubmed.ncbi.nlm.nih.gov/34318930/

“Eight studies had an open-label design, six were double-blind and placebo-controlled. Of the 41 study results contributed by included studies, about one third were at overall high risk of bias. Ivermectin doses and treatment duration varied among included studies.“

“We are uncertain whether ivermectin compared to placebo or standard of care reduces or increases mortality”

“Authors' conclusions: Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID-19. The completed studies are small and few are considered high quality. Several studies are underway that may produce clearer answers in review updates. Overall, the reliable evidence available does not support the use ivermectin for treatment or prevention of COVID-19 outside of well-designed randomized trials.”

It’s easy to understand why people where mislead by a fake study, but in 2023 we just have better data and better treatments.

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