Henderson and Hooper on Ivermectin

On July 28 (electronic) and July 29 (print edition), the Wall Street Journal published an article by Charley Hooper and me on ivermectin. At our request, the Journal published a correction that we provided on the evening of July 28 and our letter to the editor. The letter to the editor is appended below.

Because over 30 days have passed, I’m free to upload the whole article.

Here’s the article:

The Food and Drug Administration claims to follow the science. So why is it attacking ivermectin, a medication it certified in 1996?

Earlier this year the agency put out a special warning that “you should not use ivermectin to treat or prevent COVID-19.” The FDA’s statement included words and phrases such as “serious harm,” “hospitalized,” “dangerous,” “very dangerous,” “seizures,” “coma and even death” and “highly toxic.” Any reader would think the FDA was warning against poison pills. In fact, the drug is FDA-approved as a safe and effective antiparasitic.

Ivermectin was developed and marketed by Merck while one of us (Mr. Hooper) worked there years ago. William C. Campbell and Satoshi Omura won the 2015 Nobel Prize for Physiology or Medicine for discovering and developing avermectin, which Mr. Campbell and associates modified to create ivermectin.

Ivermectin is on the World Health Organization’s List of Essential Medicines. Merck has donated four billion doses to prevent river blindness and other diseases in Africa and other places where parasites are common. A group of 10 doctors who call themselves the Front Line Covid-19 Critical Care Alliance have said ivermectin is “one of the safest, low-cost, and widely available drugs in the history of medicine.”

Ivermectin fights 21 viruses, including SARS-CoV-2, the cause of Covid-19. A single dose reduced the viral load of SARS-CoV-2 in cells by 99.8% in 24 hours and 99.98% in 48 hours, according to a June 2020 study published in the journal Antiviral Research.

Some 70 clinical trials are evaluating the use of ivermectin for treating Covid-19. The statistically significant evidence suggests that it is safe and works for both treating and preventing the disease.

In 115 patients with Covid-19 who received a single dose of ivermectin, none developed pneumonia or cardiovascular complications, while 11.4% of those in the control group did. Fewer ivermectin patients developed respiratory distress (2.6% vs. 15.8%); fewer required oxygen (9.6% vs. 45.9%); fewer required antibiotics (15.7% vs. 60.2%); and fewer entered intensive care (0.1% vs. 8.3%). Ivermectin-treated patients tested negative faster, in four days instead of 15, and stayed in the hospital nine days on average instead of 15. Ivermectin patients experienced 13.3% mortality compared with 24.5% in the control group.

Moreover, the drug can help prevent Covid-19. One 2020 article in Biochemical and Biophysical Research Communications looked at what happened after the drug was given to family members of confirmed Covid-19 patients. Less than 8% became infected, versus 58.4% of those untreated.

Despite the FDA’s claims, ivermectin is safe at approved doses. Out of four billion doses administered since 1998, there have been only 28 cases of serious neurological adverse events, according to an article published this year in the American Journal of Therapeutics. The same study found that ivermectin has been used safely in pregnant women, children and infants.

If the FDA were driven by science and evidence, it would give an emergency-use authorization for ivermectin for Covid-19. Instead, the FDA asserts without evidence that ivermectin is dangerous.

At the bottom of the FDA’s warning against ivermectin is this statement: “Meanwhile, effective ways to limit the spread of COVID-19 continue to be to wear your mask, stay at least 6 feet from others who don’t live with you, wash hands frequently, and avoid crowds.” Is this based on the kinds of double-blind studies that the FDA requires for drug approvals? No.

Correction
This article has been edited to remove a reference to a study of 200 healthcare workers by Ahmed Elgazzar of Benha University in Egypt. Messrs. Henderson and Hooper relied on a summary of studiespublished in the American Journal of Therapeutics. They learned after publication that this study has been retracted because of charges of data manipulation.

Our letter to the editor, which ran in the July 29 electronic edition (July 30 print):

We, the authors of “Why Is the FDA Attacking a Safe, Effective Drug?” (op-ed, July 29), have egg on our faces. Relying on a summary of studies published in the American Journal of Therapeutics, we quoted the results from a study of 200 healthcare workers. After our article was published, we learned that this study, by Ahmed Elgazzar of Benha University in Egypt, has recently been retracted due to serious charges of data manipulation.

We retract the part of our article that relied on the data from Dr. Elgazzar’s study. But the broader point stands: There’s strong evidence of ivermectin’s efficacy in treating Covid-19.

David R. Henderson

Charles L. Hooper
Grass Valley, Calif.

READER COMMENTS

READ COMMENT POLICY

Michael Sandifer

Sep 3 2021 at 5:36pm

David Henderson,

I read the FDA warning very differently than you do. They warn against the use of formulations of the drug intended for animals, and related possible overdose risk. They promote taking it as prescribed if prescribed by a physician. I see no inflation of dangers.

Also, you’re certainly not pointing to a lot of evidence for efficacy against Covid-19. It appears much more study is needed before actually recommending this drug for this purpose.

The vast majority of drugs that suggest benefit in vitro do not in fact work in vivo. I see no mention here of the vast difference between the concentration of Ivermectin that kills Covid-19 in petri dishes versus the concentration realized in typical human dosing, which varies greatly by different cell types, etc. Rl

Also, results in small scale in vivo studies usually do not hold up. We need large, stage, double-blind, placebo controlled trials before making broad recommendations.

That doesn’t mean some doctors shouldn’t throw Ivermectin at Covid-19 cases involving extremely vulnerable patients. They can always prescribe off-label. Doctors should use their best judgment.

That said, with vaccines that protect the vast majority of the vaccinated against serious Covid-19 complications, it underlines the point that it currently makes no sense to broadly recommend Ivermectin as a treatment for Covid-19.

And just so you know, pre-pandemic I favored limiting the FDA’s authority to merely labeling drugs as safe or not, and efficacious or not. Given their performance during this pandemic, I now favor abolishing the agency. I think they’ve done much more harm than good, but the example you cite is not evidence of harm, in my opinion.

Zeke5123

Sep 4 2021 at 9:00am

it is true that ivermectin can be given in safe dosage. It might not help but hard to see how it hurts.

Likewise, there was little evidence that masking helps (still not great evidence) but the same kinds of people pushed masking on grounds it can’t hurt (despite not really knowing, especially with kids).

There is shall we say an inconsistency there.

Alan Goldhammer

Sep 4 2021 at 9:13am

If it is given at the human dose, ivermectin likely will not cause harm though there are some nasty side effects. The big question is whether it will have any therapeutic advantage. I have counted well over 100 drugs that have in vitro activity against SARS-CoV-2 but 99% of these are clinically irrelevant in terms of being a true antiviral. One has to be very cautious in extrapolating in vitro results as the Australian ivermectin data shows (too high a concentration is needed).

Sep 4 2021 at 9:21am

You are misunderstanding my point. My point isn’t that it’s effective (I’m agnostic). My point is that it can be safe and could be effective. So if I was in the hospital with covid I’d want it administered.

For what it’s worth I was vaccinated back in April.

JFA

Sep 4 2021 at 8:26pm

Why wouldn’t you want Fluvoxamine or Dexamethasone instead?

Sep 6 2021 at 1:26pm

Zeke,

Especially since you’re vaccinated, why would you bother wanting Ivermectin if you get the Covid virus? You’re unlikely to have serious complications anyway. That’s the whole point of the vaccine.

Sep 6 2021 at 6:14pm

JFA — sure. I haven’t really followed those but if same principle applies.

Michael — because sometimes there are breakthrough cases and if it were severe enough for me to be in the hospital my vaccination status wasn’t doing enough work.

Walt French

Sep 20 2021 at 5:54pm

I’m curious why you’d want Ivermectin, rather than any of the thousands of other drugs that could be used off-label, none of which present terrible risks and none of which have been shown to have ANY efficacy.

Charley Hooper

Sep 7 2021 at 2:01pm

Alan Goldhammer,

If it is given at the human dose, ivermectin likely will not cause harm though there are some nasty side effects.

Yes, but…

Ivermectin itself is one of the safest drugs available. The side effects seen with ivermectin are usually a result of the dying parasite. If you successfully kill a parasite living in your body, there might be problems with your body dealing with the destroyed parasite. Don’t blame those side effects on ivermectin.

bob

Sep 6 2021 at 3:14pm

Thank the FDA for that! The FDA has instructed pharmacies to NOT fill doctor prescriptions for ivermectin. So people have no choice but to get the animal version. Merck and the FDA came out against Ivermectin only after the US government contributed $356 million to Merck to develop MK-7110, an anti-COVID drug. This occurred after Merck purchased the rights to MK-7110 for $425 million in a deal announced on December 23, 2020. The chances of this drug receiving approval by the FDA are very high. The chances of Ivermectin successfully competing against MK-7110, if Ivermectin is also approved, are also high. It is, therefore, logical that a multi-billion dollar industry will use its immense lobbying, media, and advertising power to prevent this. The smoking gun here is that Merck was the original developer of Ivermectin, but now that their old drug is generic and no longer profitable, it is being tossed under the proverbial bus. https://www.thedesertreview.com/opinion/letters_to_editor/big-pharma-uses-big-tobaccos-strategy-to-defeat-ivermectin/article_fc17022e-9ba6-11eb-8c7b-633764c1bf9e.html

Sep 7 2021 at 2:07pm

bob,

So true. People think that ivermectin is Merck’s drug (it is) and therefore Merck would want to push ivermectin for COVID-19. But because of the reasons you lay out, and others, such a rules against off-label promotion, Merck (1) does not want to promote ivermectin for COVID-19 and (2) doesn’t want to appear to be promoting ivermectin for COVID-19.

David Henderson

Sep 7 2021 at 3:57pm

I was waiting to reply until I had talked to my co-author, Charley Hooper. He generally has the sense to save documents we work from. I didn’t save the original FDA warning. He did. The FDA warning that you can find now is way toned down compared to the one we commented on.

It seems that we had an effect.

We’ll be writing about this soon.

Scott Sumner

Sep 3 2021 at 6:40pm

This is interesting:

“In 115 patients with Covid-19 who received a single dose of ivermectin, none developed pneumonia or cardiovascular complications, while 11.4% of those in the control group did. Fewer ivermectin patients developed respiratory distress (2.6% vs. 15.8%); fewer required oxygen (9.6% vs. 45.9%); fewer required antibiotics (15.7% vs. 60.2%); and fewer entered intensive care (0.1% vs. 8.3%). Ivermectin-treated patients tested negative faster, in four days instead of 15, and stayed in the hospital nine days on average instead of 15. Ivermectin patients experienced 13.3% mortality compared with 24.5% in the control group.”

Maybe I’m missing something here, but why did only 0.1% of ivermectin patients enter intensive care, given that 13.3% died? That’s less than 1% of those who died. In contrast, fully 1/3 of control group patients who died were first put into intensive care.

Sep 3 2021 at 7:36pm

The paper you link to is from the Australian researchers who first published in vitro data on the use of ivermectin. As noted in my post below, their results cannot be achieved in vivo because the concentration needed for antiviral activity is 10 fold higher than can be acheived by human dosing. This is a drug that doesn’t work and has some pretty bad side effects if abused (which it is here in the US). Just as with hydroxychlorquine, people are chasing an illusive cure down a rabbit hole.

Michael S.

Sep 4 2021 at 7:31am

This can’t be an answer to Scott Sumner’s comment

Nor does it chime with the quoted article, which is clearly about in vivo studies

Are you claiming the authors are quoting fake studies?

Dylan

Sep 4 2021 at 8:11am

The first study they link to is an in vitro study that shows the concentrations needed to get the effect are much higher than what you get with the approved human dose, and indeed getting to that high of concentration in vivo is probably impossible.

gwern

Sep 4 2021 at 1:26pm

I believe the intended link was “Ivermectin Treatment May Improve the Prognosis of Patients With COVID-19”, Khan et al 2020 https://www.archbronconeumol.org/en-ivermectin-treatment-may-improve-prognosis-articulo-S030028962030288X which is a retrospective correlational study. Which is useless, but at least it’s *probably* not completely fake like so many ivermectin studies have already turned out to be (not just Elgazzar).

Sep 4 2021 at 7:35am

I second that. The mortality rate needs to be lower than the other rates, or we’re talking about completely different samples

Ted Durant

Sep 4 2021 at 10:58am

Co-morbidity. I haven’t followed through to try to find the data or summary tables, but given that all of the subjects were showing COVID-19 symptoms, I’m going to guess that the population was mostly elderly. Plenty of people die without passing through ICU.

Sep 4 2021 at 1:28pm

Sure, but why the vast different between ivermectin and non-ivermectin patients? Less than 1% vs. 1/3. I suspect I’m missing something here as it’s not my area of expertise, but the data looks really weird to me. No one has answered my question.

(And I have no view on the effectiveness of ivermectin.)

Econymous

Sep 4 2021 at 2:04pm

You also can’t have 0.1% of 115 people.

steve

Sep 4 2021 at 9:43pm

There are a lot of red flags here. There were only a bit over 100 pts. Way too small. It says that none of the Ivermectin pts developed pneumonia or cardiovascular complications but 13.3% still died. Why the heck did they die? Pulmonary issues have been our primary issue with these patients. They go on to multi-organ failure but not having pulmonary issues is uncommon. Scott is correct that most people who die have a long ICU stay first. Sudden death, probably thromboembolic and people who were DNR and did not want prolonged care are about the only ones who dont make it to the ICU.

Looking at the history of papers on Ivermectin there were some early ones that claimed nearly miraculous rates of cures. At least one of those was retracted (Egyptian or Brazil, cant remember) and some others had obvious statistical issues. Most were small. Also, some early studies showed no effect, but those were also small. Now we have larger studies with controls and generally better methods. They are largely showing Ivermectin has no effect or a small one. There are some more studies coming out so I would wait before claiming it is useless but I will be surprised if we see a very large effect.

Which is what those of us in the field actually caring for these pts expected. We all tried HCQ and AFAICT every ICU doc on my team has tried Ivermectin. We just haven’t seen any effect. If it was as miraculous as claimed we would have seen it. We saw the same thing with HCQ. We were desperate and willing to try anything, but after a while when you dont see any effects you stop.

Sep 7 2021 at 2:09pm

Scott Sumner,

Different studies. Sorry for the confusion. Space didn’t allow us to explain that the results were from different studies.

Sep 3 2021 at 6:43pm

Guys, there is no evidence that ivermectin works against clinical SARS-CoV-2 infections. It is not safe in terms of how people in the US are taking the drug. They are swallowing veterinary doses that are too high for humans and there have been a lot of calls to poison control centers as a result.

As I noted to the earlier post when you just had the letter published, the clinical pharmacology of ivermectin in no way supports its use against humans for SARS-CoV-2. The early in vitro experiments showing inhibition required levels of ivermectin that cannot be achieved! Here is the reference: https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.1889

You might have referenced the recent RCT of masks done in Bangladesh that was not available when you wrote the WSJ op-ed. Masks when properly worn work.

Sep 3 2021 at 9:41pm

You write:

You might have referenced the recent RCT of masks done in Bangladesh that was not available when you wrote the WSJ op-ed.

Yes, we might have. But the point is that the FDA recommended masks without such a study. That’s part of our point. They aren’t consistent.

Sep 4 2021 at 9:34am

The entire debate about masks was confused from the outset when the public health authorities stupidly said that masks were not needed. They then shifted and said they were. We know that masks work otherwise surgeons and nurses would not wear them in the OR. There is a huge amount of data on the utility of masks and one of the first observational studies came out in the middle of 2020 showing that in two German towns with differing dates of mask mandates, the town that first adopted the mandate demonstrated far better control of the virus. There is data from schools and other institutions as well as in Taiwan and South Korea where the wearing of masks is almost universal.

One of my favorite resources for masks is Aaron Collins’s YouTube Channel. Collins is an aerosol scientists who began testing a large variety of masks just over a year ago. He has a good spread sheet that shows the results of his studies. Most of the Korean KF94 masks perform as well as the gold standard N95 mask. Personally, I use the KF94 mask when going out to the store and other enclosed places. They fit well and are easy to breath and speak with.

I agree with you that the FDA moves way too slow and is inconsistent in this area. There is also considerable confusion between the role of FDA and NIOSH (who regulate masks for industrial use). The larger problem for me is that most people do not know how to select a mask or properly wear one. At the store yesterday, there was a guy walking around with the mask just over his mouth, the nose was uncovered. I’ve seen countless people wearing surgical or procedure masks without crimping in the left and right edges where there are large openings for air to be inhaled and exhaled.

MikeP

Sep 4 2021 at 10:41am

We know that masks work otherwise surgeons and nurses would not wear them in the OR.

Surgeons and nurses wear masks in the OR to prevent coarse droplets from falling into open incisions and, secondarily, to keep fluids from the patient from reaching their noses and mouths.

While those are very good reasons to wear masks in the OR, they are all large scale effects. Why would anyone think that is evidence that such masks are useful for capturing micron scale aerosols?

Sep 4 2021 at 11:57am

It is but one example of infection control and there are others. If you look at countries where there is universal mask wearing and slower rate of vaccination than in the US, you do not see the same level of SARS-CoV-2 infections (specifically Taiwan and South Korea; I’ll leave aside China as they take draconian measures whenever an outbreak occurs). Here is one data point: at the beginning of August, South Korea had only 14% of the population fully vaxxed with 39% having had one shot. Is it magic that there are so few cases or is it that the masks work to a very high degree when they are properly worn and there is universal usage. I opt for the second reason.

This debate was finished over a year ago for most of the world outside the US. That it is still being argued here and in other forums baffles me. Of course, I am easily baffled these days by a variety of goings on in the US.

Midwesterner

Sep 6 2021 at 2:58am

@Alan Goldhammer

I’m skeptical of any study that looks at geographical areas and their mask policies and then infers mask effectiveness based on Covid cases.

In clinical studies, researchers conduct controlled tests on a large sample. They work hard to eliminate or understand confounding variables and then compensate for them.

Studies that look at geography, mask policies, and Covid spread always examine a small sample of geographical areas that are not controlled in any meaningful way. The areas are often arbitrary, and do not take into account non-homogeneities between the two areas being compared. In fact, they often try to hand wave away those confounding variables by acting like those geographical areas are homogenous enough to not have to attempt to address any of those issues.

Take, for example, two towns, both without mask policies early in the pandemic. One town implements a mask mandate, and the other does not. But before the mask mandate goes into effect, a super spreader event occurs in the town without a mask mandate. A similar event does not occur in the town that imposes a mask mandate.

A study like the one you’re describing would make it look like the mask mandate is effective. But the initial conditions for these two towns were fundamentally different, and Covid spread in the town without the mandate could be driven overwhelmingly by the super spreader event instead of a mask policy.

Any number of variables could explain the difference: genetic make up of the population, population age, public transit usage rates, travel patterns of residents to and from the area, prior exposure to Covid, willingness to get tested, quality of the data kept and tracked by governments, etc. Studies that examine Covid cases between two arbitrarily chosen areas usually don’t even try to deal with these variables.

Furthermore, even if you did have a smoking gun study that shows two identical populations where the only difference was mask wearing, you can’t make the inference that wearing a mask is in fact driving the difference. What if people that would otherwise go out decide to stay in, simply because they don’t wear a mask? If governments required people to wear paper bags over their head to go outside, I imagine such a policy could limit the spread of Covid simply because most people prefer not to wear paper bags on their heads, not because paper bags confer any significant Covid protection.

But that’s always the conclusion drawn by these studies: masks are effective at preventing the spread of Covid. The conclusion that should be drawn is that masks can sometimes limit the spread of Covid among two arbitrarily compared populations.

You can easily find populations that wear masks consistently and have for a while with massive Covid spread (India) and populations with little mask wearing and little Covid spread (some mid-western states). I’m sure you’d be quick to point out the differences between those two areas, and I’d agree with you 100%. It’s apples to oranges. So are the two towns side by side. So are two neighborhoods in the same city. But these studies lie and act like these non-homogeneities don’t exist.

It’s not a hard thing to study. Get a group of 100 people who have not had prior Covid infection or vaccination, and have them interact with a person who is Covid positive in a controlled environment. Have them play pattycake for 5 minutes. 50 of them wear a mask, 50 of them don’t. See how many test positive afterward. Scale the study up to however many participants it takes to eliminate the confounding variables.

But that would answer the question once and for all, and then the political football would be gone, so I’m not holding my breath waiting for someone to conduct such a study.

Sep 6 2021 at 1:32pm

MikeP,

Masks don’t offer perfect protection. No one argues otherwise. Of course there are some particles that can get inbetween the threads of a mask. The point is, the mask cuts down on the number that are transmitted. It lowers the viral load that is spread. That’s sometimes the difference between the virus gaining a foothold or not during initial infection, or between an infection that overwhelms the immune system versus one that is more easily handled.

Sep 7 2021 at 12:29am

Of course there are some particles that can get inbetween the threads of a mask. The point is, the mask cuts down on the number that are transmitted. It lowers the viral load that is spread.

Except that every clinical trial and RCT finds that masks have no effect on the spread of viruses in the studied settings.

Since you seem to have an expertise in the micro behaviors of how a mask might conceivably work, maybe you can answer some questions:

I understand how the momentum of large droplets might drive them into masks to be captured, but I do not see how micron-scale aerosols with virtually no momentum within the ambient air will be driven into the mask. After all, virtually all the air one breaths while wearing a surgical mask goes around the mask, not through the mask. How can the aerosols actually contact the mask, overcoming airflow and boundary layer effects?
If the aerosols do get captured in the mask, what keeps the aerosols from reaching an equilibrium in the mask so no further aerosols are captured?
If the aerosols do continue to get captured in the mask, what keeps the viruses from leaving the mask with the water in the aerosols as it evaporates?

I have never heard an answer to any of these questions. To me it looks like the explanation of masks working among the asymptomatic is completely made up. Seriously, there are either good answers to all of these questions, or masks are supposed to work by magic.

Don’t get me wrong. On or around the symptomatic, at least for a few minutes, I can believe that masks do something. The large droplets of the symptomatic have momentum and limited range, so if they are captured or deflected, they are less likely to reach someone far away.

It is the claim that masks do anything whatsoever among those without symptoms, where any virus is carried by aerosols, meaning any virus goes exactly where the air goes — i.e., out of someone’s airways and into someone else’s airways — that is not believable. Unless there is something very fortuitous going on, a mask will rapidly reach some equilibrium where virus expelled from the wearer’s airways behind the mask equals virus expelled from the wearer outside the mask. Since surgical masks were never designed to filter and capture viruses, I have to believe that nothing fortuitous is going on.

Sep 7 2021 at 2:23pm

Masks have failed in virtually every randomized controlled trial (first with influenza and then with COVID-19) until the most recent study from Bangladesh. And the total effect seen is…drum roll…a 5% reduction in infections for those wearing cloth masks, which are the most common.

John Ioannidis looked at studies published in the journal Anaesthesia and he found very high rates of fake data from India (54 percent) and some other countries.

Did the Bangladesh study rely on fake data? Can it be replicated?

Sep 6 2021 at 1:34pm

David,

Respectfully, this is a very weak point. Of all the awful things the FDA has done during this crisis, mask recommendations is certainly not one of them. How about delaying vaccines hitting the market? They should have been available months earlier. That’s a real tragedy.

Sep 6 2021 at 5:46pm

Respectfully, this is a very weak point. Of all the awful things the FDA has done during this crisis, mask recommendations is certainly not one of them.

No it’s not. It’s a strong point. It shows in one FDA statement that the FDA is inconsistent: it rejects ivermectin partly on the grounds that there haven’t been sufficient studies and embraces masks even though it knew at the time that there hadn’t been sufficient studies. One of our major points in the piece, which was in our (not used) title, is that the FDA is unscientific.

How about delaying vaccines hitting the market? They should have been available months earlier. That’s a real tragedy.

I agree. Embrace the power of “and.” We don’t have to choose only one of the FDA mess-ups. In your view, how many months earlier?

Sep 10 2021 at 3:09pm

I understand the concept of “and”. I never suggested you didn’t recognize such serious errors the FDA has made. My point is that the controversy over masks isn’t worth mentioning. Wearing a mask is of trivial cost, and such masks have been worn by billions of people in prior pandemics, and by medical professionals on a daily basis for many decades.

Sep 7 2021 at 2:11pm

And the FDA has removed the reference to masks in the latest version of the Ivermectin warning.

Sep 4 2021 at 8:58am

I’ve just read what the study did and let’s just say this is not strong evidence at all for wide spread mask usage.

1. The study also encouraged social distancing (ie just not masks). So we have two variables; not one.

2. The study involved extensive intervention re properly wearing masks but it noted this faded over time. This reality needs to be considered in any policy (ie whether something works is based off of actual usage).

3. This study found that cloth masks provided zero benefit (counter to point 1 since if you saw a difference between surgical and cloth masks but both parties social distance seemingly the difference is the mask). But we’ll the vast vast majority use cloth masks.

4. Finally it’s far from clear how effective the observation was given the large number of people in this study (both in control and treatment group). That is, there were allegedly 330k people in the study yet I highly doubt there was an effective way to keep track of 330k to really make an apples to apples comp. Also note that only 11k of the 330K were actually tested in this non blind study. That seems..rife for unintentionally putting a thumb on a scale.

I very much doubt the FDA would accept a study of such low quality for efficacy

Besides that, FDA requires not just efficacy but safety. Once again with masking, there seems to be a complete disregard of the harms done (eg for kids).

Sep 4 2021 at 10:22am

Appending to Zeke5123’s list…

5. There is no reduction of symptomatic seroprevalence in any cohort under the age of 50 for the presumably higher quality surgical masks.

Now which is more likely:

a. Masks do anything useful whatsoever.
b. People educated about wearing masks change their behavior according to their risk.

We are continuously promised scientific proof that masks work. Indeed, in the words of Live Science in this instance, “Huge, gold-standard study shows unequivocally that surgical masks work to reduce coronavirus spread.” Yet again and again the studies show only marginal effect and, under modest scrutiny, they show results consistent with masks doing nothing at all to reduce asymptomatic transmission.

Aaron

Sep 3 2021 at 7:37pm

I think the issue with the drug is that people are taking doses meant for horses because they’re easier to obtain. The problem there is that the doses are too high for human consumption and causing people to go to the emergency room. Currently there is some promising evidence that it might be effective, but to be “scientific” here the sample sizes are too small so far. Normally I’d be on board with criticizing the FDA, but they and the Who have actually suggested follow up studies on the drug. Honestly, this is coming across as another silly partisan fight over COVID related matters (nothing against the authors here though). It’s kind of bizarre how whether one drug or another is effective or not keeps becoming some mark of belonging to a particular cultural-political tribe.

Sep 7 2021 at 2:33pm

Aaron,

Yes. Good point. I have a friend who despised President Trump. One day my friend was positively giddy because some negative data had come out about hydroxychloroquine. To many, it’s just data. To him, his tribe had just scored a goal. And further, he should have been sad that thousands and thousands of people might die from the lack of good treatments.

Sep 4 2021 at 6:24pm

Alan Goldhammer writes above:

This debate [about the efficacy of masks] was finished over a year ago for most of the world outside the US. That it is still being argued here and in other forums baffles me.

I’m surprised by his unscientific attitude. That baffles me.

gofx

Sep 5 2021 at 1:23am

David, you are so right. There is more “science” supporting ivermectin as a helpful treatment for Covid than masks being effective at preventing it. Ivermectin was not just a random choice, rather it has historically known anti-viral properties. If you look at mask studies, especially the ones BEFORE the pandemic, they essentially conclude that common surgical masks do not protect against the transmission of respiratory viruses. They are worn to stop droplets, not aerosols. The papers cover a variety of situations, surgery, dental offices, and other patient encounters. The “face coverings” that people wear are even less effective than the blue surgical masks, and people do not wear them or surgical masks properly. Have you ever seen the guys with big, thick beards wearing a mask? Its hilarious. And I am vaccinated, and had masks before the pandemic! Also, some of the papers have noted potential harm in chronic mask wearing such as self-contamination, aerosolization of your own droplets, and inhalation of microplastics. By the way, what is Fauci’s latest recommendation, two masks or three? I’ve lost track.

It amazes me that this relatively simple decision problem escapes the public health officials. They are saying (especially early on), “We don’t have any early treatments for you, but don’t take a known, safe prescription drug with billions of historical doses which has some evidence that it may be helpful to some people. Just wait until you get sicker, then go to the hospital.” Now hopefully, with more mono- and poly-clonal antibody treatments becoming available, people do have more early choices, however ivermectin, because it operates and a more “general” level, may be more “broad spectrum” than antibody treatments that may have a hard time trying to keep up with variants.

Alan Goldhammer— Mask wearing has been consistently high in Japan and Korea, something like 98% in Japan, yet if you look at the case curves you see fluctuations and viral waves as in other countries. How is this possible?

Sep 5 2021 at 6:35am

Ivermectin was used as an anti-parasitic (not anti-viral) medication in humans. That doesn’t mean it wouldn’t work against Covid, but it’s not obviously a no-brainer to me that if my doctor tells me I have a respiratory virus, I should ask, “Oh… do you have de-worming medication that can treat that?”

Seems like you’d want dexamethasone or some other corticosteroid instead. And with better evidence now available, perhaps doctors should be giving out fluvoxamine.

“Mask wearing has been consistently high in Japan and Korea, something like 98% in Japan, yet if you look at the case curves you see fluctuations and viral waves as in other countries. How is this possible?” I think mask have some effectiveness and are not completely useless (mainly because the 5 micron cutoff for aerosol has been shown to be meaningless, with particulates of at least 100 microns showing “aerosol” behavior), but I don’t even think Alan (who overstates his case almost every time he posts) is saying that they are 100% effective. There’s also variation in where people wear mask, as well. Maybe there would be much less transmission if people wore them 100% of the time (and no, I am not suggesting people do that). You could instead look at the data from Japan and Korea and say “they had a LOT fewer cases, maybe mask work.”

Sep 5 2021 at 12:02pm

Depends on the mask. My guess based on data is that some masks help (not massive but not negligible). Other masks are basically useless.

Sep 6 2021 at 1:40am

JFA,

Please do not just look at media articles on ivermectin. They are biased and politicized. If you look at the research into ivermectin (and masks), especially BEFORE 2020 you’ll see quite a different tone. I will excerpt an article from the Nature.com website from the “The Journal of Antibiotics”, volume 70, pages 495–505; published in 2017 by Andy Crump as an example: (Underlines are mine).

Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations

“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.97 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.”

So pre-pandemic you have previous research and well-stated pharmacological antiviral mechanisms discussed. And now we have some research worldwide that is suggestive of efficacy in all three stages of Covid (infection, viral replication, cytokine storm). Do we know if it works for everyone at all times? No drug does that. But David’s point is the dismissal and refusal to seriously investigate the drug by health authorities is perplexing. This is why the field of Public Choice in economics came into being. Its not just “horse medicine” or for scabies.

Finally, there are many reasons why Japan or Korea have lower Covid stats than other countries. Population size, island/peninsula, age distribution, population health (eg. Number of diabetics, overweights, other co-morbidities etc.) You have to control for all that. By looking at the time series for a country, those controls are not needed. If mask wearing is constant and nearly universal as it is in Japan, yet infections/cases fluctuate substantially and generally in the way that other countries fluctuate, then mask efficacy is a harder argument to make.

Sep 6 2021 at 7:44am

Yes, I have read several studies (including literature review articles) on Ivermectin. It doesn’t seem effective against Covid. Looking through about 8 references in the article on the “wonder drug” (you really got to careful with that kind of hype), not one was reported on data where ivermectin was used on patients to treat the diseases you listed. Here’s one quote from a paper saying Ivermectin could be used to treat STDs: “While the concentrations of ivermectin necessary for this inhibitory action in vitro are higher than what is achieved distal to absorption sites in current human therapy, topical application may allow therapeutic use of ivermectin against sexually-transmitted infection”. That’s not what I would consider strong evidence. I’m not saying conventional wisdom of 40-years can’t be overturned, but when an article starts “Recent research has confounded the belief, held for most of the past 40 years” your BS antennae should start throwing warning signals. Pair that with all the research on Ivermectin in humans for Covid that shows it’s not effective and research suggesting more efficacy for other drugs (e.g. dexamethasone, fluvoxamine, and monoclonal antibodies), I still confused as to why people are hyping ivermectin.

For masks, you would also need to control for how people are interacting with each other, which certainly varies even with prevalent masking. Japan saw it’s biggest surge starting in mid-July. One might think the Olympics (and it’s impact on people’s interaction) might have had something to do with it (saw the same thing in UK with the soccer tournament). You certainly want to control for things, but human interaction seems to be something you didn’t mention in what to control for.

Sep 6 2021 at 10:22pm

The point is not why people are “hyping” IVM, its why the “authorities” are so uninterested in even considering it, especially when actual clinical physicians and studies report some success. Are all the observations just the placebo effect? And not only are they uninterested in it, they are calling it an unsafe drug meant for horses! You should look at flccc.net or c19ivermectin.com for the list of studies. Many clinicians who use ivermectin also recommend use of other compounds as well, depending on the phase of the disease. The MASK+ protocol at flccc.net outlines how they use ivermectin, fluvoxamine, and methylpredneselone among others (you and others will be happy that they are “pro-mask too!). They disagree with you. They believe that the studies and their own clinical experience show efficacy of IVM. This whole issue is not about ivermectin, it is about corrupt, sclerotic control-freak, non-humble “public health” authorities. These are the people that hitched there wagon to remdesivir. Geez. I am certain that they will attack fluvoxamine as it gains popularity.

Regarding masks, no I don’t have to control for human interaction. This is precisely the point. If mask wearing is relatively constant and human interactions increase and cases explode, then well, that doesn’t look too good for masks. Japan in on their third peak, kind of like Israel. Israel didn’t hold the Olympics, and anyway, the Tokyo Olympics did not have spectators, but it doesn’t matter.

Sep 7 2021 at 7:08am

I’ll check out the references you gave. On the mask: just because spectators weren’t allowed in the stands doesn’t mean that the interest in the event doesn’t lead to, for example, viewing parties. You always have to control for changes in human interaction. The only time changes in human interaction would be irrelevant is if a mitigation measure was universally followed (that means even inside the home) and if it was 100% effective. I don’t think anyone is claiming that masks are 100% effective at preventing spread. You always have to control for the variables of interest that will affect the outcome.

Sep 6 2021 at 11:04am

I agree with not reading popular media. Go directly to the medical and research journals and people who use the drug. In the lab Ivermectin has some positive effects, but at levels that are toxic for people. If you look at published studies what you find is that early, generally poorly done studies showed spectacular results for ivermectin, nothing like we saw when clinicians used it here in the US. Follow up studies that are larger and more rigorous have shown little or no effect. A couple more yet to come out but I am not expecting to see much.

Steve

Todd Kreider

Sep 10 2021 at 3:25pm

JFA wrote: “You could instead look at the data from Japan and Korea and say “they had a LOT fewer cases, maybe mask work.””

Japan had the lowest per capita testing among the OECD and South Korea was a bit higher. At least through the end of 2020, polls showed 85% of Japanese were wearing masks, not 98%. Almost all wear surgical masks, not cloth, yet there were large increases in winter (as with most places in the Northern hemisphere), spring and summer.

Lawrence

Sep 5 2021 at 9:58am

David, thank you for writing your original article and the correction! This kind of back-and-forth argumentation is exactly what’s been missing as a result of the suppression of debate during the Covid scare. And debate, after all, is an integral and absolutely necessary part of the scientific method.

Sep 5 2021 at 2:55pm

You’re welcome.

Chris

Sep 5 2021 at 1:03pm

Honestly, it was shameful of the WSJ to publish anything by you concerning what drugs are or are not effective in treating COVID. You have no medical training, nor are you versed in understanding the relevant clinical trials or interpreting their results. You should not be using your position as a professional economist to lead people to believe you have some specialized knowledge of clinical trials of drugs. You aren’t even referencing legitimate, completed studies for your data, which is dangerous in its own right.

The facts are:

1. We don’t have reliable studies on whether or not the drug is effective at preventing COVID at doses that are safe to consume.

2. We know that there are usually negative consequences to taking any specific drug, from opportunity cost, to side effects, to conflicts with other medications, that could make taking an unstudied drug particularly dangerous.

3. We know that articles like yours questioning the FDA and doctors have directly lead to a number of poisoning cases as people treat themselves with veterinary doses.

your article does nothing to prove or encourage others to prove the effectiveness of the drug as a COVID treatment. It does undermine the expertise of trained scientists and doctors making them less effective at treating people’s COVID symptoms. It does lead people to seek out treatment on their own, against the wishes and recommendations of the medical profession, leading, in some cases, to significant harm.

David, you’re a smart man; did you not think of the possible consequences of your actions, or were you just so excited to own the libs (or in this case, trained scientist and medical professionals) that you thought the risk of other people dying of poisoning was worth it?

Sep 6 2021 at 6:03pm

Honestly, it was shameful of the WSJ to publish anything by you concerning what drugs are or are not effective in treating COVID. You have no medical training, nor are you versed in understanding the relevant clinical trials or interpreting their results.

Of course, I disagree or I wouldn’t have co-authored it. And the key verb is “co-authored.” My co-author does have a lot of education and experience in evaluating drugs and testing of drugs. This is division of labor.

You aren’t even referencing legitimate, completed studies for your data, which is dangerous in its own right.

False. Many of the studies were completed, which is why the articles we referenced were published.

The facts are:

1. We don’t have reliable studies on whether or not the drug is effective at preventing COVID at doses that are safe to consume.

2. We know that there are usually negative consequences to taking any specific drug, from opportunity cost, to side effects, to conflicts with other medications, that could make taking an unstudied drug particularly dangerous.

3. We know that articles like yours questioning the FDA and doctors have directly lead to a number of poisoning cases as people treat themselves with veterinary doses.

On #1, it depends on what “reliable” means. RCT? No. But we make many major life decisions without basing them on RCT studies.

On #2, I agree.

On #3, I don’t have evidence on that. Do you? If not, it is shameful for you to make that suggestion.

your article does nothing to prove or encourage others to prove the effectiveness of the drug as a COVID treatment.

How would you know that? Don’t you think that there are people out there who would love to prove us wrong?

It [our article] does undermine the expertise of trained scientists and doctors making them less effective at treating people’s COVID symptoms.

It might undermine their alleged expertise. I’m just not sure whether to put a negative or a positive sign on that undermining.

It [our article] does lead people to seek out treatment on their own, against the wishes and recommendations of the medical profession, leading, in some cases, to significant harm.

It could cause harm. It could also work. It could also cause doctors to experiment with smaller doses. It could even cause doctors to prescribe ivermectin for human patients so that they don’t use horse-level doses.

David, you’re a smart man;

Thank you, Chris.

did you not think of the possible consequences of your actions, or were you just so excited to own the libs (or in this case, trained scientist and medical professionals) that you thought the risk of other people dying of poisoning was worth it?

That wasn’t my thinking at all. My thinking that motivated me is to point out that the FDA, which recognized the safety of ivermectin for 35 years, was now claiming it’s unsafe and it didn’t apply the same methodology to masks.

Regarding the risk of people dying of poisoning being worth it, I don’t have a view. I think it’s people’s right to decide whether it’s worth it. Clearly, you think ivermectin doesn’t work to help with Covid. What if you turn out to be wrong. Have you thought through the risk of leading people away from an effective drug that could save their lives? If not, why not?

Sep 7 2021 at 12:25am

You overstate your coauthor’s expertise. Mr. Cooper is a market analyst with a degree in engineering and engineering economics whose work at Merck was in market analysis, not trials or testing. More than anyone, he should understand the limits of what a drug is tested and authorized to treat, but is, by no means, an expert on drugs and their use. So we have two economists, one of whom has experience marketing drugs, using your platform as an economics writer to undermine the FDA’s testing process and the opinions of doctors and actual medical experts with actual expertise.

Some of the trials have been published, some are in the process, some have been retracted. There are apparently two larger trials being conducted but they are not complete. Those seem to be designed to be more consistent and rigorous, and other trials have been pretty small groups and a wide range of quality. And while the review you cited is positive on the evidence, another from the Cochran library is considerably less positive on the available evidence. Without larger scale clinical trials, there’s a lot of unknowns in terms of outcomes, dosages, drug combinations, etc.

We know that there have been a spike in poison control calls in multiple states (a quick Google search found Missouri and Texas) because of people taking the animal dose of the drug. Those people are not just magically deciding a deworming medication for sheep will stop COVID: they are getting their information from the internet and articles like yours in a major publication are giving a false sense of reliability to that information. Again, neither you nor your coauthor have the expertise to make claims as to the effectiveness or safety of taking a specific drug: you are parroting a study that itself notes that it is good that larger clinical trials are taking place. And one of that study’s major data points has since been retracted. Do I know that someone will read your opinion article and poison themselves? No. Have people read articles similar to yours and tried to medicate themselves? It seems so from the hundreds of poison control calls reported.

You clearly don’t trust those with expertise and experience to make the correct decisions in which treatments to recommend. To what end do you suppose people that have trained for years and worked their lives in the medical profession helping people would withhold a treatment they believed was safe and effective? To argue that multiple health organizations and a multitude of medical professionals are working against the best interest of humanity by withholding an effective drug is to argue that there is essentially a large scale conspiracy against saving lives taking place, being enacted by people who have generally worked their entire adult lives to help people.

Good doctors will not base their medical treatments on your opinion article in the WSJ. They will base their treatments on actual studies and the recommendations of the various organizations charged with evaluating drug safety. The medical community is already looking for new and better treatments, as can clearly be seen in both the numerous trials referenced in your article and the significant decrease in COVID mortality from the first days. How your laymen’s reading of a study review is going to impact any medical professional’s choices, I can’t comprehend. It’s far more likely that it will lead someone to believe that it will cure them of their own symptoms, preventing them from getting adequate treatment (since almost all of the studies you referenced included other drugs as well as hospital care, yet you don’t mention any of that.)

You make the assumption that I’ve made a decision on the effectiveness on Ivermectin in use for treating COVD, but my whole point is that you and I aren’t medical professionals or specialists in drug trials. I don’t know if it’s effective, or at what dose it is, because there does not appear to be enough consistent evidence for the medical community to know these things. I will rely on the experts on this and if I get COVID, will rely on my doctors to use safe and effective treatments.

lastly, the FDA article you are unhappy with really isn’t that extreme. It’s a brief, easy to understand article asking people not to take animal grade ivermectin because of the known side effects of doing so. You may not like the wording they’ve used, but people really have been significantly harmed by taking an incorrect dose or taking it while also taking other drugs (you cherry pick one rare health issue noted in the study while ignoring the other drug interaction issues they mention and also ignore that most people up till this year took human doses rather than horse doses). That’s why they specifically recommend discussing it with a doctor and getting a prescription filled by an actual pharmacist. That’s not an extreme recommendation and to argue that the FDA is being too controlling by making that recommendation is nonsense.

Sep 7 2021 at 1:34pm

Chris,

I’ll address your first paragraph here. You said:

My last name is Hooper, not Cooper.

I’ve worked in the pharmaceutical industry for 32 years. A big part of my job is creating forecasts for new drugs. I need to tell my clients something such as, “Your new drug will sell 100,000 units by time X.” It would be hard for me to do that if I couldn’t read and understand the results of clinical trials. In addition to reading and understanding clinical trial results, I need to be able to understand the reactions of physicians, patients, payers, and the FDA. I need to be able to predict what’s going to happen before it happens.

Next, you claim that I help to undermine the FDA’s testing process. The FDA doesn’t test drugs, biopharma companies test drugs. The FDA reviews the drug application and then decides whether to approve the new drug or new indication. This is one reason we wrote this article! If the FDA doesn’t have a sponsor company to submit an application for ivermectin for COVID-19—and it will likely never happen because ivermectin is generic and there’s no money in it—the FDA will never approve ivermectin for COVID-19. The FDA’s process has a huge gap in it and generic products are left to die, which means that we don’t get the benefit of the latest thinking.

Assume for a moment that ivermectin does have a benefit for a new use, such as COVID-19. The FDA has effectively locked us out of ever benefiting from that information because the FDA is a bureaucracy and new uses for old products have no clear path toward approval.

Further, you state that I undermine the expertise of actual doctors and medical experts. You may have missed this, but there are actual doctors and medical experts who are saying the same thing: ivermectin appears to offer some benefit against SARS-CoV-2.

You also stated that we may have hurt patients who took ivermectin and didn’t need it or took doses that were too high. But we never made any such recommendations! If I say that Herceptin appears to work for breast cancer, I’m not telling a certain patient to take Herceptin for her breast cancer nor am I recommending that she take a particular dose.

Sep 6 2021 at 6:08pm

Michael Sandifer writes above:

Zeke,

Especially since you’re vaccinated, why would you bother wanting Ivermectin if you get the Covid virus? You’re unlikely to have serious complications anyway. That’s the whole point of the vaccine.

It seems that Michael Sandifer is setting a new standard and expecting others to follow it. It is this:

If, because you’re vaccinated, you’re unlikely to have serious complications from getting the virus, and you get it, you shouldn’t treat it with drugs that might work. Am I understanding him correctly?

Sep 20 2021 at 5:58pm

We have recently witnessed similar promotions—azithromycin, chloroquine and hydroxychloroquine are some—where political leaders have grasped at straws offered up from the scientific community, only to have the hopes dashed. Chloroquine probably saved ME when I had malaria—I know it was a great drug for its purpose—but I’m appalled at how the discussion of it was not a balanced consideration of its pros and cons, but rather what political posture a person trusts.

This screed continues in that disgraceful tradition. Months after the low quality of “pro-IVM” studies were disclosed, the authors cling onto a one-sided view, then shift to a political point that the disgraced evidence would prove if it were correct.

Political positions are fair game; the FDA is certainly not without fault. But using EconLib as a forum where faulty, weak and simply not-ready-for-prime-time arguments are used to promote those political positions is a recipe for terrible policy

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