recent Ivermectin study retracted over "spreading misinformation"

Analyzing the issues with the study and how this retraction is being presented.

A few nights ago I had a video open from Dr. Mobeen’s interview with Dr. Patterson and Dr. Yo. When I started watching I noticed that Dr. Mobeen had a livestream going with the title “Miami Ivermectin Study Was Flawed and Withdrawn”. Curious enough, I clicked on the link and began watching the later half of the livestream.

The livestream was covering a recently released study that suggested that Ivermectin reduced mortality. However, the livestream focused on discussing the study’s retraction and the hit piece put out by the AP in response to the retraction.

Now, I personally never looked at the study in detail because only the abstract was available, and so I didn’t provide it much leverage until I would be able to see the study for myself. However the study has been circulated extensively on both Twitter and even here on Substack. Interestingly, the first author and one of the other authors has taken to Twitter to criticize people’s misinterpretations of their own study.

Iakov Efimenko @AesBrah

@PierreKory Great afternoon, I'm the first author of that paper, I believe the data and the study is being misrepresented and misinterpreted. Let's have a discussion.

Unfortunately, it appears one of the other authors has deleted his tweets. Fortunately for us, we have the power of print screen and paint.

Ivermectin doesn’t seem like it can catch any breaks. Any studies that validate one side’s position may be overlooked for serious methodology flaws while any study that refutes a position must be viewed under a microscope.

However, since we need to work from a framework of science and facts, we should always remind ourselves that we should be skeptical of any study. In fact, it may be even more important to be critical of the studies that support our position, especially if it means that we may lead to blind spots in our thinking.

What’s unfortunate is that the media doesn’t seem to consider this same principle important. In fact, the media is well-known to double down on any narrative that targets those who dissent from mainstream viewpoints. Aside from the mRNA vaccines there’s no other clearer example than Ivermectin.

So I thought it would be important to go over the issues with the study and how the media has reported on the withdrawal.

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A Brief Look at the Flawed Study

First off, I’ll provide Dr. Mobeen’s perspective on the study and provide my own critiques. Dr. Mobeen also provides his own takes on how the media is reporting on this retraction.

The study’s title is the following:

Treatment with Ivermectin Is Associated with Decreased Mortality in COVID-19 Patients: Analysis of a National Federated Database

It was published in Elsevier’s International Journal of Infection Disease after first being included as a presentation for the journal’s conference. It’s interesting that the AP linked to the journal and the conference yet did not link to the actual study. This happens quite often with mainstream media articles who may not even bother to provide the actual title and just references “a newly released study from X”.

Also, credit should be given to the authors for indicating that the publishing of the article was not done with their permission, so there’s at least some credit where credit is due for pointing that out.

As for the actual paper, since only the abstract is available we can only break it down based on the information provided.

The study was a retrospective study. Retrospective studies are observational studies that look at data after a patient has been given a treatment and has had an outcome recorded. It usually involves going into a database and filtering patient information based on specific variables such as treatments provided, demographics, and comorbidities. Here, the researchers looked at a database called TriNetX and filtered patients into two groups; one who was given Ivermectin and no Remdesivir, and one given Remdesivir and no Ivermectin.

There’s a large misrepresentation when it comes to the type of study one conducts or what the results mean. There’s this blind assumption that the only proper study is a peer-reviewed, double-blinded, randomized control trial, and that all other studies are not worth their weight in paper. This type of heuristic approach has pervaded so much of the COVID discourse- you can see it just by looking at the responses to Dr. Pierre Kory’s tweet. The issue is that this type of heuristic approach quickly dismisses anything that doesn’t fit the gold standard rather than examining a study for what it’s worth. In fact, this type of approach leads people to neglect even reading the actual paper for the substance. If someone sees “peer-reviewed, double-blind RTC” then that gives them the go ahead to accept the research at its word instead of “trusting, but verifying” the actual evidence.

In the case of a retrospective study a researcher may notice that there’s some unusual discrepancies in outcomes with certain patients. Such a signal may lead researchers to investigate for some correlative evidence of said noise. In which case they may conduct a retrospective study. Although this methodology may find correlative evidence this type of study suffers from many fallacies.

For one, researchers are relying on the evidence provided by attending clinicians instead of relying on their own evidence. That means that any wrong or improperly recorded clinical information may lead to false interpretations when used in a retrospective study. It also does not take into account confounding variables that may not be properly filtered for. In some respects, retrospective studies rely on the notion that the only differences between cohorts are the measures that the researchers are looking at. In this case, patients may only be categorized along lines of Ivermectin use or Remdesivir use.

The researchers did make note that they tried to control for several variables:

We controlled for the following demographics, comorbidities, and treatments that may affect COVID-19 survival outcomes: age, gender, race, ethnicity, nicotine use diabetes mellitus, obesity, chronic lower respiratory disease, ischemic heart diseases, tocilizumab, glucocorticoids, or ventilator use.

But we can see that there is still a large difference in age between the two groups:

Within the ivermectin cohort, average age was 51.9 + 17.8 years, 43% were male, 60% had glucocorticoids and 1% required ventilator support. In the remdesivir cohort, average age was 62.0 + 16.0 years, 54% were male, 64% had glucocorticoids and 2% required ventilator support.

The Ivermectin group also skewed more female while the Remdesivir skewed more male. However, the most egregious misstep is that Ivermectin was given in an outpatient setting while Remdesivir was provided inpatient with hospitalized patients. These type of variables may not be fully accounted for in retrospective studies and may alter the results of such a study.

Here’s an overview of many of the variables that may affect retrospective studies (taken from Talari, K. & Goyal M):

So we can see that there are many issues with looking at retrospective studies. However, that does not mean that they should be immediately discredited. Instead, it means that studies should be examined for their own merits and limitations.

Retrospective studies have made major contributions to the world of medicine and have provided invaluable insights (taken from Talari, K. & Goyal M):

Retrospective studies have a place in research and many of them have helped shape the clinical practices. An example of the utility of retrospective studies is the landmark paper that described the association between smoking and lung cancer.8 The study revealed that smokers were at a significantly higher risk of developing carcinoma of the lung compared to non-smokers. Such a hypothesis could have never been put through the test of a randomised trial.

Another landmark retrospective chart review in the 1990s found that spinal anaesthesia was faster, easier to administer and more comfortable and safe for the patient for caesarean section, as compared to epidural anaesthesia.9 Until then, epidural was the preferred mode of anaesthesia administration in caesarean section, but we have since seen a paradigm shift towards spinal anaesthesia; by 2009, 85% of obstetricians in the United States were using spinal anaesthesia for caesarean section and another 11% were combining it with epidural.10

Retrospective studies provide many insights, but they are not without their own flaws. Both need to be taken into account when examining retrospective studies.

For even more credit to the Ivermectin researchers, they use this findings to suggest further RCT research into Ivermectin. It appears from one of the author’s tweets (although deleted for some reason) that their RCT results did not provide any significant evidence of Ivermectin’s effectiveness.

Ivermectin use was associated with decreased mortality in patients with COVID-19 compared to remdesivir. To our knowledge, this is the largest association study of patients with COVID-19, mortality and ivermectin. Further double-blinded placebo-controlled RCTs with large samples are required for definite conclusion. In the future, if more publications are published with the similar result to the current analyses, the certainty of evidence will increase.

Taken together, there are a few ways of interpreting the different results. It could be that RCT’s controlled for confounding variables and eliminated other factors such as age and treatment setting. More homogeneous groups may have removed the masking done by confounding variables. However, we won’t know the full extent of their research until their results are published, and we may actually find some flaws in those studies as well.

So what do we do with this study? Well, the withdrawal would suggest that we don’t take this study into consideration. However, we have to keep in mind that the study was withdrawn because the evidence does not live up to scrutiny. As it stands it appears that peer review has led to the study’s withdrawal, which means that we need to understand what the reviewers saw as flawed data. Again, it means that the evidence does not live up to scrutiny. We should not discount the study for the sake of it not being peer-reviewed (more heuristic assumptions) but because peer review revealed flawed methodology.

We also have to remember that one study does not the whole field make. It’s the totality of all the studies and the proper examination of them that provides us the abilities to make solid, sound judgement.

Even if this study is removed, this does not discredit Ivermectin on its own. We also have to remember that its conclusions, even if true, do not validate Ivermectin as well. It’s the totality of the evidence and science that should be taken into account.

No matter what we view of this study and withdrawal, lean into studies with a deal of skepticism and weigh any study along the type of study, the merits of such a study, and the limitations that come with such a study.

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A Brief Analysis of AP’s Smear Piece

I’ve taken up quite a bit of time with the analysis of the abstract so instead of providing a full analysis of the AP paper I will provide a few points of concern so that you all can read the paper for yourself and come to your own conclusions. I think Dr. Mobeen also does a good analysis in his review as well so most of this will be supplemental. Remember that this paper shouldn’t be read within the context of refuting the Ivermectin paper but the narrative it tries to present with the study.

1. No link to the actual abstract. Although this is quite common in mainstream articles one should question why the title of the article was included without the actual link to the abstract. Personally, it makes me think of the Chris Cuomo clip where he says that it is “illegal” for people to view the Wikileaks documents for themselves (this is the best clip I can find unfortunately so disregard the ALIENS clip). I would assume that this was done to prevent people from finding the abstract and making assumptions on Ivermectin’s effectiveness. As a news outlet, this lack of transparency is very telling, especially if the intent is to prevent viewers from seeing the information for themselves. It’s even more telling that the article links to articles that refute Ivermectin’s effectiveness and indicates severely biased reporting. Be very careful about articles that have this lack of transparency.

2. Be careful about the evocation of heuristic terms and phrases. Vacuous, empty phrases do not make for good stand-ins for actual evidence and science. Be careful when you see articles that use such phrases without providing much context. Here, the writer refers to peer-reviewed as “a much more rigorous process” without explaining what makes it more rigorous (it’s more likely that the reviewers only gave a cursory glance to the abstract as a part of the conference). You’ll also see that the writer needed to be told that “correlation does not equal causation”. Again, another vacuous statement that provides nothing of substance. It’s also weird that the writer needed to be told of this considering how often the phrase is evoked. More importantly, avoid assuming that “fact-checkers”, by virtue of proclamation, are in fact checking for facts. Be extremely critical of those who purport to disseminate facts as a valid argument.

3. Avoid appeals to authority. When looking at papers and articles take care not to lend too much credence to one’s resume. More experienced, formally educated clinicians and researchers may be better at assessing research, but that type of assessment should shine through within their writings and arguments. If no such indication can be seen don’t assume that you should take someone’s words because they are heavily credentialed. Remember, it is the fact that someone is credentialed that means that they should be able to provide more substantive arguments, and that’s what people really need to look out for. One of the main authors of the Ivermectin study is a medical student and this has been used as a point of criticism. Again, the study should stand on its own irrespective of the author. In this case the evidence is flawed not because of the author but because the evidence suggests so. Avoid falling back on ideas of heuristics and appeals to authority when possible. People would be wise to keep this in mind in order to become a more discerning reader.

4. Watch out for absolutist language. In the tweet above, and in many other tweets I have seen, many people have looked at this abstract as validation for Ivermectin’s effectiveness when there was no study available. The inability to evaluate the study on its merits meant that more people should have been more skeptical of the results. Unfortunately, that doesn’t appear to be the case in those who tweeted out the study without properly evaluating it. The same can be said with Dr. Zamora’s tweet as well. Even if their RCT trials show that Ivermectin does not work, there’s no way he can definitively state that it does not work at all. Remember that the field of science requires that all evidence be evaluated in order to come to an agreement. No one study overrides any other studies that come before it regardless of whether it supports or refutes our notions of a drug or concept. Try avoiding taking such hard lined stances. The precautionary principle should always be at play.

5. Criticize ad hominem attacks that assume the intelligence of the readers/viewers. One of the greatest sins of the AP article is its assumption that disseminators of the article are too naïve to understand that they are spreading misinformation. Irrespective of the study’s methodology, we can’t fully fault people’s interpretations of the abstract as many of the fault lies on the researchers for not having checked for such flaws within their own research. As Dr. Mobeen remarks, the researchers appear to be attacking people who have misinterpreted the abstract when the study’s faults as a whole are what led to the abstract and study. It’s ironic that they would rather criticize people rather than take ownership of how poorly conducted their study was. But you’ll also see that the AP article invites another doctor (Dr. Mark) who makes the claim that, “no credible doctor would prescribe ivermectin”, which really just highlights that this paper served more as a hit piece than to really disabuse any forms of misinformation. It’s quite alarming that many within the medical community would speak so lowly of their peers and of the public. Good science should stand on its own without requiring the need to attack dissenters for their stupidity. Unfortunately, this idea tends to be more overlooked than utilized.

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What to make of the situation

Overall, I really don’t know what to make of this situation. Many in Dr. Mobeen’s comments are suggesting that this piece was released in order to besmirch Ivermectin and those who disseminated this abstract. Part of my biases lend me to believing this assessment, but I’m trying to take care not to lean too heavily into this idea. Also, considering how volatile the Ivermectin arena is I don’t see why doctors, especially a fledging medical student, would risk future employment to provide some one-up against Ivermectin supporters. Part of me also believes that the authors never caught such egregious mistakes beforehand and are now trying to recover after having their pants pulled down. In which case I find it extremely unprofessional to attack people for misinterpreting research that probably should have never been released.

I do, overall, find it extremely concerning how often the media will try to shame people who’s ideas stray from the establishment’s talking points. It’s ironic how often the media will take up the crown of “fact-checkers” in order to push a narrative rather than provide informative, substantive examinations of actual facts and evidence. This “fact check” by the AP doesn’t provide anything of value aside for a narrative to beat Ivermectin proponents over the head with.

Hopefully this study’s retraction highlights the need for critical thought and to not take everything at face value. We should also take care to be cautious of any information we find on social media and to make sure that we view things through a veil of skepticism and check on the veracity of information ourselves.