Author Topic: Ivermectin  (Read 3425 times)

Offline PlatinumGuy

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Ivermectin
« on: February 28, 2021, 10:16:48 PM »
did you know that Ivermectin protects almost as well as the vaccine according to the latest data?

LOL
״וזה כלל גדול: שישנא אדם כל דבר שקר. וכל מה שיוסיף שנאה לדרכי השקר – יוסיף אהבה לתורה.״ - אורחות צדיקים

Offline biobook

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Re: Ivermectin
« Reply #1 on: February 28, 2021, 10:30:00 PM »

P.P.S. While I don't believe that masks are the answer (they are not needed in many cases and not enough in other cases), besides there is something anti-social about wearing a mask, did you know that Ivermectin protects almost as well as the vaccine according to the latest data?

Thanks for this information!  I have trouble keeping up with all the latest data, and appreciate when others bring something like this to my attention.  Can you post the data that you base this on?  Or a link to the research that's been published?
TIA

Online Euclid

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Re: Ivermectin
« Reply #2 on: February 28, 2021, 10:38:13 PM »
Thanks for this information!  I have trouble keeping up with all the latest data, and appreciate when others bring something like this to my attention.  Can you post the data that you base this on?  Or a link to the research that's been published?
TIA
there's a video on youtube






(this a joke - referencing an earlier post)

Offline Yehuda57

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Re: Ivermectin
« Reply #3 on: February 28, 2021, 11:20:35 PM »
Thanks for this information!  I have trouble keeping up with all the latest data, and appreciate when others bring something like this to my attention.  Can you post the data that you base this on?  Or a link to the research that's been published?
TIA

He'd provide you the evidence, but unfortunately it's all in the abstract
Quote from: ExGingi
Yehuda57 needs to spew a certain amount of sarcasm in order to survive through the day.

Offline Chaimel6

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Re: Ivermectin
« Reply #4 on: February 28, 2021, 11:47:45 PM »
Okay, it's my [real] job to study research. So here goes.

Ivermectin

Ivermectin is a relatively safe drug and is being used extensively by doctors around the world to prevent and to treat COVID-19. There are 62 published studies on Ivermectin including 21 RCTs (randomized controlled trials; which is considered the gold standard).

Prevention
11 of the 62 studies are on its prophylaxis properties (i.e. prevention) with an average improvement of 89% vs the control group.

Example: RCT: "PEP trial for asymptomatic close contacts of COVID-19 patients, 203 ivermectin patients and 101 control patients. 7.4% of contacts developed COVID-19 in the ivermectin group vs. 58.4% in the control group, adjusted odds ratio OR 0.087, p < 0.001. "
FYI a p value of less than 5% (0.05) is the standard proof of efficacy. This is not as good as the (Moderna or Pfizer) vaccines (which is about 93%-95% effective) but is still not too bad.

If you would like to read the rest of the studies they are available at https://ivmmeta.com/ it gets updated in real time and you can easily drill down into the details, for example, to see mortality improvements in early usage, etc.

So, if anyone you know is at high risk, they should ask their doctor about Ivermectin.
« Last Edit: March 01, 2021, 12:21:54 AM by Chaimel6 »

Offline biobook

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Re: Ivermectin
« Reply #5 on: March 01, 2021, 12:46:53 AM »
Okay, it's my [real] job to study research. So here goes.

Ivermectin

Ivermectin is a relatively safe drug and is being used extensively by doctors around the world to prevent and to treat COVID-19. There are 62 published studies on Ivermectin including 21 RCTs (randomized controlled trials; which is considered the gold standard).

Prevention
11 of the 62 studies are on its prophylaxis properties (i.e. prevention) with an average improvement of 89% vs the control group.
What does that mean, 89% improvement?  If the goal is prevention of disease, what does improvement mean?

Quote
Example: RCT: "PEP trial for asymptomatic close contacts of COVID-19 patients, 203 ivermectin patients and 101 control patients. 7.4% of contacts developed COVID-19 in the ivermectin group vs. 58.4% in the control group, adjusted odds ratio OR 0.087, p < 0.001. "
FYI a p value of less than 5% (0.05) is the standard proof of efficacy. This is not as good as the (Moderna or Pfizer) vaccines (which is about 93%-95% effective) but is still not too bad.
Which reference is this? 

You said that ivermectin is almost as good as the vaccine in protecting against covid.  This study treated 203 people with ivermectin, while IIRC the Pfizer clinical trials treated 20,000 people with the vaccine.  Do these different numbers affect how you compare the two studies?
Quote
So, if anyone you know is at high risk, they should ask their doctor about Ivermectin.
I know some pregnant women who are concerned about catching the virus.  Do you have any information on ivermectin in pregnancy, whether it affects the mother or her fetus?

Offline Chaimel6

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Re: Ivermectin
« Reply #6 on: March 01, 2021, 02:38:23 AM »
What does that mean, 89% improvement?  If the goal is prevention of disease, what does improvement mean?
In medicine, you compare a group that took an intervention with a control group (those who didn't get this intervention), and you see how it worked out for both.

The 89% is the average improvement across all 12 studies. In prevention a 89% improvement means that 89% fewer people who were taking Ivemectin got the disease vs those who did not take Ivermectin.
Quote
Which reference is this? 
See the link.

Quote
You said that ivermectin is almost as good as the vaccine in protecting against covid.  This study treated 203 people with ivermectin, while IIRC the Pfizer clinical trials treated 20,000 people with the vaccine.
That's an intelligent observation. In fact, by now Pfizer has data for tens of millions of people. That's a lot. This doesn't compare to the 203 people who participated in this study or the 7,011 people across the 12 different studies publishd on Ivermectin as a preventative. This means that we don't know that there is exactly an 89% improvement. There is a +/- standard of error. The real number might be less or more. The 89% is my best guess using the data we have now. The p-value, i.e. the probability that the effect is totally random is very low.

Quote
Do these different numbers affect how you compare the two studies?I know some pregnant women who are concerned about catching the virus.  Do you have any information on ivermectin in pregnancy, whether it affects the mother or her fetus?
I am not a doctor, but I would hesitate to recommend Ivermectin for a pregnant woman unless she is in actual danger. That's because there is one side effect of Ivermectin which I suspect might have a slight effect on a male fetus.

For a pregnant woman:

A. Invest in N95 masks. These are the best type for protecting the wearer. It should fit properly. I would even use one with a valve (which are more comfortable but only protect the wearer) if it means that she would wear it more.

B. Take the maximum known safe dose of Vitamin D daily, which is about 4000 IU/day, in case she is deficient (that would be pretty common). The studies on pre-exposure prophylaxis show an average of a 42% improvement with Vitamin D. That's a very rough number with a high +/- margin of error, even more than the Ivermectin studies. In the different studies the improvement varied from 8%-90%.

C. Avoid high risk events such as weddings, crowded indoor areas such as plays. If she needs to go away to extended family for the Seder, it wouldn't hurt if they get tested a few days before Pesach.

D. Consider getting the vaccine after the first trimester.


If Ch"v she does come down with COVID-19:

A. Consider taking a catch up dose of Vitamin D (it can take a few months for Vitamin D in the blood to build up to optimal levels of 30 ng / dl+). In the two studies with published positive results in early treatment, 80,000 IU D3 was taken by mouth once a month.

B. Take 50-100 mg zinc sulfate a day.

C. Consider getting convalescent plasma treatment early. If there is a Bikur Cholim in your city, they may know where to go for this. These treatments seem to be about 65%-70% (+/-) effective.


FYI: I am not a doctor but a researcher. I study stats and data. My primary expertise is discovering stff that is not yet well known. Often it's undiscovered because it's counterintuitive.

Please check with her doctor.
« Last Edit: March 01, 2021, 02:41:58 AM by Chaimel6 »

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Re: Ivermectin
« Reply #7 on: March 01, 2021, 10:16:24 AM »
FYI: I am not a doctor but a researcher. I study stats and data. My primary expertise is discovering stff that is not yet well known. Often it's undiscovered because it's counterintuitive.

Please check with her doctor.
Thank you so much for your informative post, which - based on it's length, must have taken some time to post.

What strikes me is the levelheadedness of it. Many times, when someone calls themselves a researcher, their post will look something like this:

Quote
Avoid all vaccines
Stop eating sugar
Stay in your underground bunker
Kill all vaccinated people
Take 100,000,000 grams of Vitamin A, B1, B3, B98, Melatonin, Co-qu-10, Red 40, and breath mints every day
Have a cyanide pill handy
Monkeys don't fly unless you put them on airplanes

Offline Lurker

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Re: Ivermectin
« Reply #8 on: March 01, 2021, 10:30:44 AM »
Okay, it's my [real] job to study research. So here goes.

First of all, I want to apologize for dismissing your claim about Ivermectin out of hand, like it was another hydroxychloroquine shill. You are obviously much more familiar with the studies than the average person, myself included.

That said, I have a few issues and/or questions regarding your claim that Ivermectin protects almost as well as the vaccines.
  • The study you gave as an example appears to imply that Ivermectin was given after exposure, to prevent infection from setting in. The Elgazzar (RCT) looks like the same MO. The last prophylaxis RCT (Chahla), "received Ivermectin orally 2 drops of 6 mg = 12 mg every 7 days, and Iota-Carrageenan 6 sprays per day for 4 weeks." I'm just a guy off the street when it comes to science, but to me, it seems like comparing any of these usages to a one or two shot vaccine would be apples and oranges.
  • The NIH doesn't find the studies on Ivermectin reliable for the following reasons:
    Quote
    However, most of these studies had incomplete information and significant methodological limitations, which make it difficult to exclude common causes of bias. These limitations include:

    • The sample size of most of the trials was small.
    • Various doses and schedules of ivermectin were used.
    • Some of the randomized controlled trials were open-label studies in which neither the participants nor the investigators were blinded to the treatment arms.
    • Patients received various concomitant medications (e.g., doxycycline, hydroxychloroquine, azithromycin, zinc, corticosteroids) in addition to ivermectin or the comparator drug. This confounded the assessment of the efficacy or safety of ivermectin.
    • The severity of COVID-19 in the study participants was not always well described.
    • The study outcome measures were not always clearly defined.
    These sound like many of the same issues we had with other drugs in the past, most of whom proved to be ineffective against Covid, despite some positive studies. It seems very premature to push the drug with these issues still outstanding and with the history we have with repurposed drugs for Covid treatment/prevention.

I'm not going to say that Ivermectin doesn't work. I don't know. I'm still not sure if the Zelenko protocol works. But neither of them is a vaccine, and I don't think it's responsible to push their use as a treatment without further data.
Failing at maintaining Lurker status.

Offline biobook

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Re: Ivermectin
« Reply #9 on: March 01, 2021, 11:58:59 AM »
It's refreshing to hear from someone who understands statistics!  I had a basic statistics course years ago, but all the data being thrown at us in covid-times is overwhelming.  Welcome to DDF!

A few questions:



The 89% is the average improvement across all 12 studies. In prevention a 89% improvement means that 89% fewer people who were taking Ivemectin got the disease vs those who did not take Ivermectin.

You seem to be using the word "improvement" in a way different from its everyday English meaning (to get better).  Is this a usage from the field of statistics?  from epidemiology?  Can you give a source for this usage? (Maybe it's in the glossary of one of your textbooks?)

Quote
See the link.
The link you gave was to a website that lists hundreds or thousands of research articles.  It would be more helpful if you would post a link to the actual article you're referencing, and/or the author and title of the article, so that people reading it here can find it. 
(Meanwhile, I did find the specific article you were referencing by searching on that page for the particular data points you mentioned.  I'll make a separate post for that.)

Quote
That's an intelligent observation. In fact, by now Pfizer has data for tens of millions of people. That's a lot. This doesn't compare to the 203 people who participated in this study or the 7,011 people across the 12 different studies publishd on Ivermectin as a preventative. This means that we don't know that there is exactly an 89% improvement. There is a +/- standard of error. The real number might be less or more. The 89% is my best guess using the data we have now. The p-value, i.e. the probability that the effect is totally random is very low.
So you're saying that a study with tens of millions of people is in some way better than a study with 200 people?  Is there a way to convey this difference?  That is, is there a way to quantify that the p<.05 for the large Pfizer study is different from the p<.05 for the Ivermectin study?  Or is this something that statistics people just use more words to describe qualitatively?

Also: You're somehow grouping together the 7,011 people in 12 different studies, each of which was done in different ways.  Is that a meaningful way to analyze data? 

Quote
I am not a doctor, but I would hesitate to recommend Ivermectin for a pregnant woman unless she is in actual danger. That's because there is one side effect of Ivermectin which I suspect might have a slight effect on a male fetus.

Whoa!  What are you hinting at?  Does it cause some kind of deformity in the fetus?  Is it more likely to cause a miscarriage?  What is "a slight effect"?   

You're suggesting here that Ivermectin is NOT as good as a vaccine for protecting a pregnant woman.  And in our community, where birth control is rare, basically every woman spends most of her life being either pregnant or being potentially pregnant.  So are you saying that Ivermectin is as good as the vaccine for adult men, but not for adult women?

Offline biobook

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Re: Ivermectin
« Reply #10 on: March 01, 2021, 02:15:04 PM »

Prevention
11 of the 62 studies are on its prophylaxis properties (i.e. prevention) with an average improvement of 89% vs the control group.

Example: RCT: "PEP trial for asymptomatic close contacts of COVID-19 patients, 203 ivermectin patients and 101 control patients. 7.4% of contacts developed COVID-19 in the ivermectin group vs. 58.4% in the control group, adjusted odds ratio OR 0.087, p < 0.001. "
FYI a p value of less than 5% (0.05) is the standard proof of efficacy. This is not as good as the (Moderna or Pfizer) vaccines (which is about 93%-95% effective) but is still not too bad.

This is the Shoumann study "Use of Ivermectin as a Potential Chemoprophylaxis for COVID-19 in Egypt" Article can be found on the site Chaimel6 referenced, from the Source or PDF link near the facebook icon on this page:
https://c19ivermectin.com/shouman.html

In the vaccine studies, people were injected with vaccine and let loose into the world, as the scientists waited months to see whether any of them were exposed to a covid-positive person and developed the disease.

This study took a much faster approach to testing a drug:  When a person was diagnosed with covid, they gave ivermectin to their family members, to see whether it could prevent covid symptoms over the next 2 weeks in those people who had a known recent contact with a covid-positive person.

Although it's a good question, I'm not certain that they chose the best way to study it.  Let's say there were two people from two different families who were diagnosed with covid: Jack and Jill, and each lives with an extended family of 10 people.  There are two possible ways they could have done the study:

Method 1:
Jack's family:  5 family members given ivermectin, 5 family members untreated
Jill's family:  5 family members given ivermectin, 5 family members untreated

Using this method, they would then count up how many covid cases occurred among those who were treated with ivermectin (n=10)

Method 2:
Jack's family: 10 family members given ivermectin
Jill's family:  10 family members not treated

They actually chose this method.  That is, in some families, all the family contacts got ivermectin, and in some families none of them did.  This makes it difficult to interpret the results.  If all of the covid cases occurred in Jill's family, is it because they didn't take ivermectin?  Or is it because Jill's family lives in more cramped conditions, with less air flow to remove the virus?  Or because there's less cleaning going on?  Or because her relatives are genetically more susceptible to the virus?

In other words, the people getting the drug are all living in different situations than the untreated people.  How would you analyze that statistically?  It doesn't seem accurate to say that you have the same n=10 as you would have using the first method.  Maybe it would be more accurate to say that you have n=1 in this scenario, where you are statistically analyzing the number of HOMES where covid appeared, rather than considering it as n=10, where you are analyzing the number of INDIVIDUALS.  What do you think?

This study was done last summer, when the authors saw ivermectin as a stop-gap measure until vaccines would be produced.  They write " At the same time, vaccine, or specific antiviral treatment is not available until now. Both of them may need a lengthy time to be invented, preclinically and clinically examined,  approved  and  widely  produced.  Drug  repurposing  is the best possible time-worthy avenue for combating this emergent infection."

There's no reason to think that the authors of this study would be advocating for use of ivermectin in America today, now that  vaccines have become available.  They conclude that the drug is worth studying more rigorously, because it's cheap and widely available around the world, not that "it protects almost as well as the vaccine." 

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Re: Ivermectin
« Reply #11 on: March 01, 2021, 04:27:05 PM »

They actually chose this method.  That is, in some families, all the family contacts got ivermectin, and in some families none of them did.  This makes it difficult to interpret the results.  If all of the covid cases occurred in Jill's family, is it because they didn't take ivermectin?  Or is it because Jill's family lives in more cramped conditions, with less air flow to remove the virus?  Or because there's less cleaning going on?  Or because her relatives are genetically more susceptible to the virus?

In other words, the people getting the drug are all living in different situations than the untreated people.  How would you analyze that statistically?  It doesn't seem accurate to say that you have the same n=10 as you would have using the first method.  Maybe it would be more accurate to say that you have n=1 in this scenario, where you are statistically analyzing the number of HOMES where covid appeared, rather than considering it as n=10, where you are analyzing the number of INDIVIDUALS.  What do you think?



Another point to add to this is how we have seen that the results of an exposure vary greatly even within the same family and even more so between families. Without a large group this can skew the results badly.
Feelings don't care about your facts

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Re: Ivermectin
« Reply #12 on: March 01, 2021, 07:57:27 PM »
This is the Shoumann study "Use of Ivermectin as a Potential Chemoprophylaxis for COVID-19 in Egypt" Article can be found on the site Chaimel6 referenced, from the Source or PDF link near the facebook icon on this page:
https://c19ivermectin.com/shouman.html

The study is completely bogus.

Quote
The Zagazig University results reveal that out of 203 subjects in the ivermectin arm 15 contacts (7.4%) developed COVID-19 as compared to 59 (58.4%) in the non-intervention arm.

There is no way 58% of all contacts had symptomatic Covid. Data from every corner of the world contradicts that.  They either selected contacts that were already symptomatic, predisposed to symptomatic illness, or fabricated the whole thing.

Egypt isn't a respected medical authority for a reason.
״וזה כלל גדול: שישנא אדם כל דבר שקר. וכל מה שיוסיף שנאה לדרכי השקר – יוסיף אהבה לתורה.״ - אורחות צדיקים

Offline biobook

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Re: Ivermectin
« Reply #13 on: March 01, 2021, 08:38:34 PM »

There is no way 58% of all contacts had symptomatic Covid. Data from every corner of the world contradicts that.  They either selected contacts that were already symptomatic, predisposed to symptomatic illness, or fabricated the whole thing.

Egypt isn't a respected medical authority for a reason.
More convincing to critique the study, than the country in which it was done. 

The "contacts" are not random, one-time contacts.  They're family members who are living in the same household as the initial patient.  Why is it not credible that more than half would be symptomatic over the next two weeks?

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Re: Ivermectin
« Reply #14 on: March 01, 2021, 09:05:38 PM »
Why is it not credible that more than half would be symptomatic over the next two weeks?
It's extremely unlikely that 60% of household contacts contracted Covid (the rate of transmission would be much higher than 1 if that was the case)

Quote
University of Florida researchers, after analyzing 54 studies with more than 77,000 participants, found that 16.6 percent of COVID-19 patients spread the disease to other members of their household.;

https://hartfordhealthcare.org/about-us/news-press/news-detail?articleId=30113&publicid=743

And even if all contacts were infected, less than 60% would be symptomatic.

https://www.news-medical.net/news/20201009/86-percent-of-the-UKs-COVID-19-patients-have-no-symptoms.aspx

The simpler explanation is that the study is bogus.
״וזה כלל גדול: שישנא אדם כל דבר שקר. וכל מה שיוסיף שנאה לדרכי השקר – יוסיף אהבה לתורה.״ - אורחות צדיקים

Offline biobook

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Re: Ivermectin
« Reply #15 on: March 01, 2021, 10:53:35 PM »
It's extremely unlikely that 60% of household contacts contracted Covid (the rate of transmission would be much higher than 1 if that was the case)
 
https://hartfordhealthcare.org/about-us/news-press/news-detail?articleId=30113&publicid=743

And even if all contacts were infected, less than 60% would be symptomatic.

https://www.news-medical.net/news/20201009/86-percent-of-the-UKs-COVID-19-patients-have-no-symptoms.aspx

The simpler explanation is that the study is bogus.
"Bogus"?  Is this right-wing media, where name calling takes the place of thoughtful discourse?

It sounds like you're saying that the level of symptomatic infections, 58% of family contacts, sounds suspiciously high, based on the hartfordhealthcare page, which says that 28.3% of adult household members get the disease.  This article is based on a JAMA article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774102 which is a review of 54 different studies.  Among these studies, they note that "There is evidence for clustering of SARS-CoV-2 infections within households, with some households having many secondary infections while many others have none. For example, 1 study reported that 26 of 103 (25.2%) households had all members test positive."

The Egypt study had 26 households in the untreated group (112 family members), so there's no reason to expect this small sample would be identical to the average reported for 77,758 family members in the JAMA article, and it is within the range of the individual households described there. 

On the other hand, a problem with the Egypt study is that 58% of family contacts got covid in the untreated group, but that was based on symptoms only.  They did not have access to PCR tests at the time to confirm that this was covid.  But they feel the research is still valuable because the same was true for the ivermectin group, who didn't develop symptoms at the same rate. 

The authors give further limitations of this study, which they agree has its problems.  They don't seem to be lying, or intentionally misleading their readers.  They are not arguing that ivermectin should be used widely or should take the place of vaccines.  They are arguing only that it is a treatment that is worth further study, especially for countries that don't expect to have widespread access to vaccines in the near future.

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Re: Ivermectin
« Reply #16 on: March 01, 2021, 11:44:21 PM »
They don't seem to be lying, or intentionally misleading their readers.
But they are.

Based on global averages, out of 110 household contacts, you’d expect 30 Covid infections, and around 15 of them symptomatic.

This study found 4x global averages. That is an irreconcilable discrepancy.

It is either fundamentally flawed or intentionally fraudulent, and either way it is completely bogus.

Standing up for something that is way outside the realm of possibility isn’t thoughtful discourse.
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Re: Ivermectin
« Reply #17 on: March 02, 2021, 08:01:20 AM »
"Bogus"?  Is this right-wing media, where name calling takes the place of thoughtful discourse?
It is a מכת מדינה.
Feelings don't care about your facts

Offline aygart

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Re: Ivermectin
« Reply #18 on: March 02, 2021, 08:01:51 AM »
But they are.

Based on global averages, out of 110 household contacts, you’d expect 30 Covid infections, and around 15 of them symptomatic.

This study found 4x global averages. That is an irreconcilable discrepancy.

It is either fundamentally flawed or intentionally fraudulent, and either way it is completely bogus.

Standing up for something that is way outside the realm of possibility isn’t thoughtful discourse.
Sounds to me like an issue of small sample size.
Feelings don't care about your facts

Offline Chaimel6

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Re: Ivermectin
« Reply #19 on: March 02, 2021, 12:05:22 PM »
While I have read all your responses, I apologize that I don't have the time to respond in detail to all your insightful comments. In particular I would like thank biobook for encouraging respectful and thoughtful dialogue, which should be standard, especially on a Jewish forum.

A couple of points:

A. It should be the job of the NIH and/or other government agencies to fund proper trials for interventions that don't have private funding (for example by pharmaceutical companies). If some of those interventions were even half as good as advertised, a lot of lives could have been saved. Who else should fund it? The lack of such funding seems to hint that there is some degree of regulatory capture. I think we should be demanding that the government funds more of those types of trials, using exactly the same protocol that was reported as having been successful. Preferably in consultation with the researcher who discovered it, to ensure maximum likelihood of success.

B. Ivermectin may be a consideration for people who are older than childbearing age (and thus high risk) who are either waiting to receive their second dose of a vaccine, or are being advised by their doctor to avoid events such as joining their children and grandchildren for Passover even after getting vaccinated, after consultation with a doctor.

It's true we don't have perfect evidence. Still, there is no evidence that there is a global conspiracy and widespread fraud going on in favor of Ivermectin. True, there probably is a publication bias, which can be somewhat mitigated by the consideration that there has not been a single study to date showing that it was not effective. (Of course, if someone is motivated to do so, he can easily create such a study by altering the treatment protocol or cohort of patients being treated, and make it designed to fail). One reason why this is relevant is because at this stage, if a study would prove lack of effect it would be surprising and be a sort of man bites dog type of headline. Is it reasonable to assume at this point that while 100% of the 42 studies to date reported positive effects it was all because of methodology limitations?

Let's look at this a different way. I am going to try to put this in laymens terms. In statistics, the greater the magnitude of an effect, and the more consistently an effect happens, the more likely that we can rule out random. This is why when a friend tells me that he did A and got better from COVID in two days, I tell him that I know someone who took nothing and got better in one day. (When you drill down into the p-value formulas it generally boils down to consistency and magnitude.) In practically all trials that I have seen to date (consistency), Ivemectin has shown a relatively large effect (magnitude).