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Merck is also working on Molnupiravir as a treatment, and possibly other things as well. So failure of the Merck vaccine candidate does not remove conflicts of interest regarding potential utility of ivermectin in prevention and treatment.
Of course a conflict of interest by itself does not necessitate that Merck's statements suggesting …
Merck is also working on Molnupiravir as a treatment, and possibly other things as well. So failure of the Merck vaccine candidate does not remove conflicts of interest regarding potential utility of ivermectin in prevention and treatment.
Of course a conflict of interest by itself does not necessitate that Merck's statements suggesting or implying safety risks in the use of ivermectin for COVID-19 are incorrect. But the statements themselves seem to lack any clear basis and thus suggest, of themselves, that they may not be well founded.
Thanks for taking the time to go through the study and for the detailed reply.
The study you cite seems indeed to be one of the important studies. However I should note that drugs, in this case dexamethansone, are not approved due to a single study. Normally you need a large number of them and several rounds of internal review. Dexamethasome is a known drug that's used to treat inflammatory symptoms in covid cases so it does what it's known to do. IVM on the other hand works on parasites and it does so in a way that is not directly applicable to covid, namely by targeting the parasites nervous system. On top of that there is the whole dosage issue which suggests the amount of IVM, for parasite treatment that's around every 6 months, is not enough even if you increase the amount to a few times a week. In fact it was suggested that the needed amount would be toxic in humans. All of that to say that the way the drug works for covid is unkown. That doesn't mean it's ineffective but it's one of the reasons dexamethasome was approved, there we know more.
I agree that more significant effects can be found easier with smaller sample sizes. However I have not seen that with IVM, the Egyptian study was retracted so no need to get into that. The Argentinian study discussed here also has several serious flaws in my view. Several of the better studies with IVM, where there are actually randomized groups show only slight effectiveness. All of that to say I am just not convinced that IVM is highly effective, if it was the randomized studies would have picked that up and studies would consistently show it as highly effective. We're still only one year in the pandemic, so I don't expect definite answers and lots of trials on IVM are on their way, around 70 last I checked. Some better than others and when the data comes out we will see. I really hope it is effective because a cheap effective drug would be a Godsent in the pandemic, however so far I see no reason to think it is.
That's a good point with Merck and Molnupiravir. The conflict of interest remains. However the problem with this reasoning in my view is that many industries are dominated by a few big firms, think of the big four in accounting or even OPEC, that doesn't mean there is a conflict of interest every time or that there isn't one, but the argument by itself is just not convincing. The pandemic is a huge event for most industries even more so for Big Pharma and there are reasons Big Pharma is dominated by a few companies. It's just really expensive to develop medical drugs or finance trials that might go nowhere and profit takes years or even decades to roll in. There are conflicts of interest in the industry and lots of problems, I mean the health care cost in the US is just outrageous. We should be vigilant, but in the end it's like you said "Of course a conflict of interest by itself does not necessitate that Merck's statements suggesting or implying safety risks in the use of ivermectin for COVID-19 are incorrect". What convinced you you say is hte statements by Merck, which you suggest lack any clear basis. At least based on the statement I read it simply stated that company scientists took a look and where not convicned it didn't offer much reasoning beyond that. This is pretty common as a press statement, so I would be wondering what statement you thought laked a clear basis ?
Anyways thanks for taking the time, feel free to email me the statement.
Cheers
It is true, and I recognize and agree with your point, that dexamethasone in COVID-19 treatment is being used for its well-known effects--reducing inflammation. But it is also true, if I recall correctly, that steroidal anti-inflammatories of any kind were officially recommended against or even ruled out in COVID-19 treatment by the major oversight agencies until the report of the above-referenced study, and also that the official standard of care was changed as a result of that (single, but numerically well-powered) study.
I looked back at Merck's statement (here https://www.merck.com/news/merck-statement-on-ivermectin-use-during-the-covid-19-pandemic/), and maybe I was a little unfair to them, but I think their comment on "a concerning lack of safety data" seems a little disingenuous. The comment, rather artfully, raises the issue of safety - almost as if the company which knows and understands the drug best has particular concerns - but without suggesting any specific risk or basis for suspecting one.
I have not seen anything to suggest, other than the argument in the Quillette paper, that the effective dosing frequency, for ivermectin, if any, should be more than weekly. (I believe it has been shown that the half lives of ivermectin's primary metabolites are longer than the compound itself.)
I recognize some things are expensive, including new drug development and testing. And that conflicts of interest do not always result in action to the advantage of the self or the self-entity and against that of others. But the risk is present and sometimes worth considering.
You're right I think that steroidal anti-inflammatories of any kind were officially recommended against or even ruled out in COVID-19 treatment by the major oversight agencies, at least that's also how I remember it. However as the evidence shifted standards were changed, the standrard of care (I assume in the US) was as far as I remember it was not changed based on a single study, that also seems inconceivable to me.
Ah that statement is actually much better than the one I read ^^
They do raise concrete safety conerns, for example
"Patients treated with STROMECTOL for onchocerciasis may experience cutaneous and/or systemic reactions of varying severity (the Mazzotti reaction) and ophthalmological reactions.
After treatment with microfilaricidal drugs, patients with hyperreactive onchodermatitis (sowda) may be more likely than others to experience severe adverse reactions, especially edema and aggravation of onchodermatitis."
I also remember the FDA warning about how IVM could interact with other medication.
Effectiv dosing with IVM is a big debate, I think I mentioned earlier that it's unclear if any dosing would suffice. As you dig through the literature you can find studies giving IVM weekly, daily or several times daily. It really varies, I think the optimal dosage is still an open question at least as far as I can tell.
Definitely, I agree with your last paragraph. The risk is pressent and it's worth thinking about. However one needs concrete evidence for a conlfict of interest.
My only additional observation is that the Merck statements (later in their material) regarding concrete risks are just standard package insert warnings relating to the risks involved in the specific on-label treatment of the target parasites, caused principally by the effects or side effects of parasite death (particularly too much parasite death at once in individuals with more significant infestations). As far as I can tell, they have no known or suggested relation whatsoever to potential treatment of COVID-19, and so may add to the potentially misleading nature of the stated (or implied), but non-specific, safety concern regarding ivermectin in COVID-19.
The dosing is not a big debate and has been pretty well established for each different protocol, (e.g. prevention, early treatment, hospital, long Covid) https://covid19criticalcare.com/covid-19-protocols/ These are in line with dosage for other conditions such as scabies and head lice.
The Mazotti reaction is much like the Jarisch–Herxheimer reaction — not an adverse reaction to the medicine, itself, but to the toxins released with the breakdown of the killed organisms.
Any questions on safety are answered here, with pertinent references. https://covid19criticalcare.com/ivermectin-in-covid-19/faq-on-ivermectin/