[W:1210] Ivermectin cures Covid. Like, almost always.

[Tim the plumber]

 

[Tim the plumber]

You didn't even seem to read this paper you posted. From the conclusions of your own source:

This pilot points towards a potential use of ivermectin in COVID-19 which warrants further exploration under larger trials, with clinical outcomes in patients with risk factors or more severe disease. This is of particular importance for settings with limited resources given ivermectin´s low price, broad availability and scalability of manufacturing processes.

Exactly my position in this entire thread.

You don't actually expect them to really read a scientific paper now surely?

 

[bomberfox]

You don't actually expect them to really read a scientific paper now surely?

Daww how cute. Anyone who disagrees with you wants people to die. Must be fun in that conspiracy cage of yours.

 

[bomberfox]

Has anyone noticed the amount of huffy rejection of any counterpoints from others towards the op and those others trying to completely armchair this stuff? We tried the quarterback immunologist approach, 600,000+ died because people wanted to do this shit all by themselves. I think ill go with the CDC thanks.

 

[Threegoofs]

Hokay lets do some math, what the people assuming that Merck is lying, what they dont realize is small prices can lead to big profits when you increase the market size and have a sufficient marginal utility to keep up production. What ivermectin would do if it was a cure (thats a huge if) would open up another market that did not exist for the product before (which is also neglected by the folks pretending a company doing a capitalism somehow makes them worse than other companies). Opening up a new market for a drug and increasing demand for the drug would raise the price (ceteris paribus).

Now for the math: Assume the increase in demand would not lead to an increase in price, we have 160,074,267 cases worldwide according to the WHO (https://covid19.who.int/) assuming the price given by others (0.08) remains the same. Opening the new market would get $12,805,941.36 in revenue plus added trust from the public which would increase profits for their other products and grants from governments in the future. Thats a pretty good profit right there for something that cheap . I am only calculating revenue based on these parameters because i dont know the costs.

Well..Merck has little interest in a generic drug because $12M in revenue would be a money loser based on just the overhead alone. There’s a chance they could get a special approval for one indication, but that won’t eliminate the generic compound.

But it’s pretty clear that ivermectin isn’t working, and I’ll just note some of the same ivermectin cheerleaders used to be Hydroxychloroquine cheerleaders too.

 

[bomberfox]

Well... 1) Merck has little interest in a generic drug because $12M in revenue would be a money loser based on just the overhead alone.

But it’s pretty clear that ivermectin isn’t working, and I’ll just note some of the same ivermectin cheerleaders used to be Hydroxychloroquine cheerleaders too.

I was just working off the information easily obtained which is why i said (ceteris paribus or all other things being equal because when new markets open, things like price change) since every one of us were just speculating without any evidence whatsoever as to why Merck would release the statement they did. Yeah i noticed that as well, the side effects alone makes hydroxychloroquine rather terrifying for something that has not undergone the proper procedure for approval by any expert body. The op also advocated for ultraviolet light treatments as a cure all despite not being able to answer which kind of ultraviolet light has an effect on covid.

 

[Threegoofs]

I was just working off the information easily obtained which is why i said (ceteris paribus or all other things being equal because when new markets open, things like price change) since every one of us were just speculating without any evidence whatsoever as to why Merck would release the statement they did. Yeah i noticed that as well, the side effects alone makes hydroxychloroquine rather terrifying for something that has not undergone the proper procedure for approval by any expert body. The op also advocated for ultraviolet light treatments as a cure all despite not being able to answer which kind of ultraviolet light has an effect on covid.

It’s very clear why Merck issued the statement. As the original patent holder, their PR departments and staff have probably been inundated with questions about Ivermectin snd COViD, and they needed to have a standard statement to respond to public, investigators and customers requests.

It’s not complicated- they want to make it clear they’re not going to fund any research here because of futility.

 

[fireflygmf]

Well..Merck has little interest in a generic drug because $12M in revenue would be a money loser based on just the overhead alone. There’s a chance they could get a special approval for one indication, but that won’t eliminate the generic compound.

But it’s pretty clear that ivermectin isn’t working, and I’ll just note some of the same ivermectin cheerleaders used to be Hydroxychloroquine cheerleaders too.

You seem to be a person of clear reasoning and you also post sensible arguments - which I respect. Because of this, I'm curious what caused you to believe that ivermection clearly doesn't work. Is there data you can point me to that you feel suggests a negative indication? I'm asking sincerely.

 

[Mulefoot]

It’s very clear why Merck issued the statement. As the original patent holder, their PR departments and staff have probably been inundated with questions about Ivermectin snd COViD, and they needed to have a standard statement to respond to public, investigators and customers requests.

It’s not complicated- they want to make it clear they’re not going to fund any research here because of futility.

And/Or liability.

 

[Threegoofs]

And/Or liability.

Liability? Nobody is using the branded product.

 

[Threegoofs]

You seem to be a person of clear reasoning and you also post sensible arguments - which I respect. Because of this, I'm curious what caused you to believe that ivermection clearly doesn't work. Is there data you can point me to that you feel suggests a negative indication? I'm asking sincerely.

There’s no one smoking gun you can point to. There usually isnt.

But remember how this became a thing... initially, someone reported ivermectin worked against the virus in an in vitro experiement. Enthusiasm mounted among non-pharmacology types, but when it was examined a bit more, it was clear that the inhibitory concentrations were orders of magnitude greater than what you could get in tissues. So the entire concept started out as pretty sketchy, although that doesnt mean its absolutely not going to work.

Clinical studies were done though, and they showed mixed results at best, and the ones that showed benefit were pretty flawed, had so many confounders, etc.
The better the studies were (as I posted earlier from JAMA) the less the benefits. Here’s one that was trumpeted as a success out of Lancet, but the ONLY positive endpoint was self reported anosmia and hyposmia (loss of smell/taste) which is a pretty soft and subjective endpoint. That’s a pretty good clue that a larger investment is probably not going to lead to benefit.

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial

Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia...

www.thelancet.com

So we need to look at the evidence as a whole. I havent done this - it’s not my area of study, but I know who has done this, and they literally have dedicated infectious disease specialists reviewing this literature carefully who are smarter in this area than anyone on this message board. What is their take?

Look at what the NIH says. https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/ivermectin/

Loook at what the WHO says: https://www.who.int/news-room/featu...used-to-treat-covid-19-within-clinical-trials


So one might question all this and say.. hey- whats the harm in trying it? Well, there are lots of therapeutics being mobilized for use in COVID, antibodies, small antiviral molecules, etc. and all of them need viable patients to enroll into trials. Ivermectin seems to be promoted for non-hospitalized patients for whatever reason (cynically, its because everyone knows its not gonna work in sick people) but that’s PRECISELY where we want to see antibodies being used, so any ivermectin trial wont just be competing for patients, but also draining resources to a likely futile study.

 

[bomberfox]

And/Or liability.

People arent using their particular brand are they?

 

[bomberfox]

First thanks for the like spam, really <3
Secondly the reason i am hostile to the op is because the op is flailing in the wind posting dishonest tripe which only confirms his biases and ignores the rest and everyone that tries to correct him get the (you sociopath!) treatment despite being a peddler of the same crap logic that infests the wellness industry. Look look! All the shiny testimonials!

 

[Fledermaus]

DEBATE Politics... Not SPAM VIDEOS Politics

FLCCC is a Ivermectin shill site.

 

[bomberfox]

DEBATE Politics... Not SPAM VIDEOS Politics

FLCCC is a Ivermectin shill site.

Hes flailing around so badly! Its comical. Falling for infomercials for wellness supplements.

 

[fireflygmf]

There’s no one smoking gun you can point to. There usually isnt.

But remember how this became a thing... initially, someone reported ivermectin worked against the virus in an in vitro experiement. Enthusiasm mounted among non-pharmacology types, but when it was examined a bit more, it was clear that the inhibitory concentrations were orders of magnitude greater than what you could get in tissues. So the entire concept started out as pretty sketchy, although that doesnt mean its absolutely not going to work.

Clinical studies were done though, and they showed mixed results at best, and the ones that showed benefit were pretty flawed, had so many confounders, etc.
The better the studies were (as I posted earlier from JAMA) the less the benefits. Here’s one that was trumpeted as a success out of Lancet, but the ONLY positive endpoint was self reported anosmia and hyposmia (loss of smell/taste) which is a pretty soft and subjective endpoint. That’s a pretty good clue that a larger investment is probably not going to lead to benefit.

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial

Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia...

www.thelancet.com

So we need to look at the evidence as a whole. I havent done this - it’s not my area of study, but I know who has done this, and they literally have dedicated infectious disease specialists reviewing this literature carefully who are smarter in this area than anyone on this message board. What is their take?

Look at what the NIH says. https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/ivermectin/

Loook at what the WHO says: https://www.who.int/news-room/featu...used-to-treat-covid-19-within-clinical-trials


So one might question all this and say.. hey- whats the harm in trying it? Well, there are lots of therapeutics being mobilized for use in COVID, antibodies, small antiviral molecules, etc. and all of them need viable patients to enroll into trials. Ivermectin seems to be promoted for non-hospitalized patients for whatever reason (cynically, its because everyone knows its not gonna work in sick people) but that’s PRECISELY where we want to see antibodies being used, so any ivermectin trial wont just be competing for patients, but also draining resources to a likely futile study.

Ok, so regarding the in vitro study that is often brought up... Yes, you're right that the concentrations were sky high and clearly could not be used in vivo. But why do you assume it's that concentration via that mechanism only that can possibly be effective for in vivo studies?

As per your second point (some weak studies showing only mild benefits)... Why do these fewer small scale studies (and they were small scale) override the greater number of studies showing stronger signals. Should we not take the lot of studies as a whole, weight them for confidence in their quality and come to some meta-analytic (think of it as a weighted aggregate) result? Because this is what has been done, including the weaker studies, and the net result was a sign of efficacy.

I have a hard time squaring that circle, I would like the data to make sense before I dismiss something, and this doesn't make sense.

Please don't read anything other than sincere curiousity in this post... I enjoy that we have different opinions but are being civil, it's refreshing.

 

[Threegoofs]

Ok, so regarding the in vitro study that is often brought up... Yes, you're right that the concentrations were sky high and clearly could not be used in vivo. But why do you assume it's that concentration via that mechanism only that can possibly be effective for in vivo studies?

As per your second point (some weak studies showing only mild benefits)... Why do these fewer small scale studies (and they were small scale) override the greater number of studies showing stronger signals. Should we not take the lot of studies as a whole, weight them for confidence in their quality and come to some meta-analytic (think of it as a weighted aggregate) result? Because this is what has been done, including the weaker studies, and the net result was a sign of efficacy.

I have a hard time squaring that circle, I would like the data to make sense before I dismiss something, and this doesn't make sense.

Please don't read anything other than sincere curiousity in this post... I enjoy that we have different opinions but are being civil, it's refreshing.

Look... you start with a false premise- that Ivermctin inhibits COVID, that’s not true.
That casts doubt that you even have a rationale for how it works. The clinical studies have been weak, at best, so why invest in a therapy that has no known mechanism and very thin data behind it?

Metaanalyses are not that great here- most of the studies sucked snd had tons of confounders and other treatments used, so it’s a metaanalyses of oranges and apples.

Look at where those metaanalyses were published. No reputable journal wanted them, unless there’s one or more I’m missing.

Drug studies are complicated and often give really misleading results, especially when done open label or non randomized- or with selective, bad inclusion/exclusion criteria. Small studies showing benefits are regularly crushed by large well done trials. That’s why phase 2 studies that look promising turn into Phase 3 disasters *most* of the time.

 

[fireflygmf]

Look... you start with a false premise- that Ivermctin inhibits COVID, that’s not true.
That casts doubt that you even have a rationale for how it works. The clinical studies have been weak, at best, so why invest in a therapy that has no known mechanism and very thin data behind it?

Metaanalyses are not that great here- most of the studies sucked snd had tons of confounders and other treatments used, so it’s a metaanalyses of oranges and apples.

Look at where those metaanalyses were published. No reputable journal wanted them, unless there’s one or more I’m missing.

Drug studies are complicated and often give really misleading results, especially when done open label or non randomized- or with selective, bad inclusion/exclusion criteria. Small studies showing benefits are regularly crushed by large well done trials. That’s why phase 2 studies that look promising turn into Phase 3 disasters *most* of the time.

Let's say you don't understand how a car works but when you push the pedal, you notice the car moves. It's not invalid to say that gas means go and brake means stop, regardless if you know other factors.

If RCT data reveals something, why am I wrong to say that it's possible that ivermectin has benefit since the data says so, and why are you right to say I shouldn't start with that premise... The fact is that I just read the data and was indifferent prior to reading any of it. I'm not soaked in American politics so I didn't realize this was a left/right thing initially. I just looked at the data.

 

[Threegoofs]

Let's say you don't understand how a car works but when you push the pedal, you notice the car moves. It's not invalid to say that gas means go and brake means stop, regardless if you know other factors.

If RCT data reveals something, why am I wrong to say that it's possible that ivermectin has benefit since the data says so, and why are you right to say I shouldn't start with that premise... The fact is that I just read the data and was indifferent prior to reading any of it. I'm not soaked in American politics so I didn't realize this was a left/right thing initially. I just looked at the data.

I dont know what data you’re looking at that says its useful.

 

[fireflygmf]

I dont know what data you’re looking at that says its useful.

I've posted many in this thread, but I realize it is difficult to search back and find them. I don't mind reposting them at all if you are having a hard time locating them, it's become a long thread.

Since we were talking earlier about possible mechanisms I started looking at any research being done in this area. It looks like a group has started on this work and has just this month published. Let me warn you, it's technical and I beyond my paygrade to understand, but if I were to review their summary findings it appears that there are particular molecular bindings that are efficient inhibitors of IMP-α1 protein, reducing viral transport at non-toxic levels. A snippet from the conclusions:

In recent study, Caly et al. reported antiviral activity of Ivermectin against SARS-CoV-2 (∼5000-fold reduction of viral RNA) with no toxicity. They hypothesized that this reduction in SARS-CoV-2 RNA is most likely through inhibition IMPα/β1 mediated nuclear import of viral proteins which needs further work up. Therefore, in our study, we explored the comparative binding mode and inhibitory mechanism of Ivermectin against two NLS-Major and NLS-Minor binding sites of IMP-α1. Our results discovered that the ivermectin reduces SARS-CoV-2 viral transport by inhibiting IMP-α1 protein after binding with its NLS-Minor site.

It appears they used a 'molecular dynamic simulation' (MD) and published some visuals from these simulations as well. I assume this is some type of protein folding leaning algorithm made to suit molecular binding simulations.

The study: Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2

 

[bomberfox]

Ok, so regarding the in vitro study that is often brought up... Yes, you're right that the concentrations were sky high and clearly could not be used in vivo. But why do you assume it's that concentration via that mechanism only that can possibly be effective for in vivo studies?

As per your second point (some weak studies showing only mild benefits)... Why do these fewer small scale studies (and they were small scale) override the greater number of studies showing stronger signals. Should we not take the lot of studies as a whole, weight them for confidence in their quality and come to some meta-analytic (think of it as a weighted aggregate) result? Because this is what has been done, including the weaker studies, and the net result was a sign of efficacy.

I have a hard time squaring that circle, I would like the data to make sense before I dismiss something, and this doesn't make sense.

Please don't read anything other than sincere curiousity in this post... I enjoy that we have different opinions but are being civil, it's refreshing.

For the record, i think you are sincere.

 

[fireflygmf]

For the record, i think you are sincere.

Thank you for this, I appreciate it. I want everything possible to be done to fight COVID and I'm afraid that in the rush to vaccinate (vaccines are great!) we might be missing something important. Maybe ivermectin is a steaming pile if sh*t, I don't know, but I'd rather the data tell me so rather than a public statement, that's what I'm really struggling with. When public statements don't match public domain data, it's very confusing. Either they are mistaken, or they have data we don't have that they are basing their decisions are. If the latter is true, they really need to release the data they have to support the statements. It's confusing to people like me.

 

[Threegoofs]

I've posted many in this thread, but I realize it is difficult to search back and find them. I don't mind reposting them at all if you are having a hard time locating them, it's become a long thread.

Since we were talking earlier about possible mechanisms I started looking at any research being done in this area. It looks like a group has started on this work and has just this month published. Let me warn you, it's technical and I beyond my paygrade to understand, but if I were to review their summary findings it appears that there are particular molecular bindings that are efficient inhibitors of IMP-α1 protein, reducing viral transport at non-toxic levels. A snippet from the conclusions:

In recent study, Caly et al. reported antiviral activity of Ivermectin against SARS-CoV-2 (∼5000-fold reduction of viral RNA) with no toxicity. They hypothesized that this reduction in SARS-CoV-2 RNA is most likely through inhibition IMPα/β1 mediated nuclear import of viral proteins which needs further work up. Therefore, in our study, we explored the comparative binding mode and inhibitory mechanism of Ivermectin against two NLS-Major and NLS-Minor binding sites of IMP-α1. Our results discovered that the ivermectin reduces SARS-CoV-2 viral transport by inhibiting IMP-α1 protein after binding with its NLS-Minor site.

It appears they used a 'molecular dynamic simulation' (MD) and published some visuals from these simulations as well. I assume this is some type of protein folding leaning algorithm made to suit molecular binding simulations.

The study: Mechanistic insights into the inhibitory activity of FDA approved ivermectin against SARS-CoV-2

I’ll leave that to the pharmacology folks, although, TBH, in my 30 years in the field, I’ve never heard of the journal.

One piece of convincing clinical data, that’s all I need.

 

[Tim the plumber]

HOW PUBLIC HEALTH AGENCIES ARE MANUFACTURING UNCERTAINTY ABOUT EARLY COVID-19 THERAPEUTICS—AND WHY​

 

[fireflygmf]

I’ll leave that to the pharmacology folks, although, TBH, in my 30 years in the field, I’ve never heard of the journal.

One piece of convincing clinical data, that’s all I need.

I suppose that's where we begin to diverge. I won't be able to post one singular, strong and convincing study for you... that is what I've been preaching here forever, to get a large high-quality randomized, placebo controlled trial.

The reason I am not dismissing ivermectin is because of the aggregate results of many small RCTs from around the world. Each, on their own, is not something to hang one's hat on. I agree with you completely here. BUT... (and it's a big one), I find it statistically unlikely that many small separate and unconnected trials will converge to similar results, and this alignment is meaningful. This essentially is what meta-analysis represents, a quantified representation of the weighted aggregate, and the likelihood of a true signal given many data points appearing within a narrow band. If the results were scattershot, the meta would reveal no signal at all.

Like you, I still would like a high quality, large RCT to reveal the truth, but I think maybe unlike you I do find value in the strength of the aggregates.