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This content was posted on  25 Jul 21  by   Rebel Wisdom  on  Medium
Ivermectin — For and Against, Briefing Document

Ivermectin — For and Against, Briefing Document

This is a document to go alongside our new film, “Ivermectin for and against” (left). It was largely researched and written by Ed Prideaux.

Over the last few weeks, as the noise around the lab leak hypothesis, vaccines and Ivermectin has grown louder in our part of the Information Landscape, Rebel Wisdom has been hard-at-work in logging, tackling and making sense of several key claims of its threats and origins, with a particular focus on the ways these claims have divided and fractured our information ecology.

Last month, we prepared a detailed briefing book on the lab leak: the arguments on both sides, its history, and the distinct sensemaking challenge it presents for all of us. This week, in line with several key films we’ve put out on the channel — and Ivermectin Day on 24th July — we’ve put together a corresponding brief on Ivermectin: an antiparasitic that many claim could be a powerful weapon (if not a ‘miracle drug’) against COVID-19.

These are hugely consequential claims for public health, and whatever the truth, it is clear that lives are at stake. Either a promising and lifesaving drug is being suppressed — or people are being people are being told to take something that may not be as effective as claimed by its supporters.

Bret Weinstein and Heather Heying of the Dark Horse channel, Dr. Tess Lawrie of the UK BIRD Group, and Dr. Pierre Kory of the FLCCC have been some of Ivermectin’s key proponents — and they’ve faced some censorious backlash from the tech giants for it, too, with even Senate testimony from Pieere Kory being taken down by YouTube. They assert the evidence for Ivermectin is beyond doubt. Others disagree. Alongside Tess Lawrie, the film we just published features Gideon Meyerowitz-Katz, an Australian epidemiologist and data scientist who has challenged some of the data analysis on Ivermectin, and Graham Walker, an ER doctor from San Francisco who has also been diving deeply into the data.

Uncanny Valley

The central issue here for Rebel Wisdom is this: in the fractured information landscape, we are seeing almost no genuine engagement from either side. The Ivermectin advocates on one side, and the sceptics on the other, rarely speak to each other (if at all). The mainstream legacy media largely ignores the topic, for fear of “false equivalence” or going against medical orthodoxy and the alternative rarely scrutinises or challenges the arguments of advocates. Yet this isn’t how you find truth. It is the “Uncanny Valley of Truth-Seeking” that we covered in our recent newsletter.

Add to this the censorship from the tech platforms directed at people who advocate for Ivermectin, and you have a perfect storm of broken sensemaking.

Hopefully this document provides a good overview of the data for and against Ivermectin. However there are many other dimensions to the conversation not covered by this overview, powerful incentive structures, both to uphold consensus, and to challenge it, and the narrative warfare on both sides is immense, with compelling stories that can overwhelm our critical faculties. On one side is the immense weight of “medical consensus” and mainstream authority, and on the other, an equally strong narrative of Ivermectin as a rallying call and badge of allegiance, a story of plucky rebels standing up against censorship and control.

We have to be fully aware of our innate tendency to be captured, and hijacked by these powerful narratives on either side. And to also use that awareness to evaluate any truth claims made by others. This is why Rebel Wisdom has always made it a priority to be self critical and aware of our own biases, and to be suspicious of anyone motivated by excessive levels of certainty and evangelical zeal. Humility is needed.

This document will outline the key claims, and the evidence and names behind them. In and among a confusing mass of stories, podcasts and media claims, the brief will give the detailed history on what Ivermectin is and summarise the different and competing claims on what it can, could (or can’t) do.

What is Ivermectin?

Ivermectin is an anti-parasitic drug (a drug that kills and erases parasites) that was discovered in the 1970s. Drawn from soil samples, Ivermectin is on the WHO’s authoritative List of Essential Medicines and its discovery won a Nobel Prize in Medicine. Ivermectin has been used for nearly fifty years in treating a number of conditions, primarily water-borne parasitic illnesses like river blindness, and is also a mainstay of veterinary medicine.

In addressing the pandemic threat, ‘small molecule’ compounds — most famous of which are Ivermectin and hydroxychloroquine — have been overlooked at scale in favour of mass vaccinations. Small molecule treatments can be used throughout the cycle of infection: in ‘prophylaxis’ (the prevention of infection in advance, rendering the treatment a ‘prophylactic’), in early treatment to address symptoms, and in late-stage treatment once the disease has progressed, whose main indicator will be mortality.

Ivermectin for COVID-19

Despite being an anti-parasite drug — so that Ivermectin is specialised for treating a distinct kind of biological entity to viruses — Ivermectin has been promoted by many as a possible therapeutic (across all the infection cycle outlined above) against COVID-19.

Medical experts have also argued that it’s unclear why an anti-parasite drug like Ivermectin would work as an antiviral. Ivermectin works as an anti-parasite drug by binding to chloride channels on nerve and muscle cells, which are present in worm and insect nervous systems, so it paralyses the parasite. Humans do have the same channels, but only in our brains and spinal columns, and Ivermectin does not cross the blood/brain barrier so we are not exposed to it. But, doctors argue, as SARS-CoV-2 has no muscles or nerves, the reason that Ivermectin would be effective against it is far from clear.

Before launching into any studies and the drug’s relative merits and demerits, it’s worth making clear that Ivermectin hasn’t been approved or endorsed by any mainstream health institution for COVID-19. As well as the FDA, the European Health Agencies, and counterparts around the world, the World Health Organization (WHO) says it should “only be used within clinical trials”, with its evidence base unready to justify prescription in the field and clinic. The National Institutes of Health (NIH) reports that there is “insufficient data … to recommend either for or against the use of Ivermectin for the treatment of COVID-19.”

Whether this is a correct reading of the available data is a technical and scientific question that will be addressed by the competing claims below.

In-vitro evidence

Hopes began with a study by Caly et al in June 2020, whose authors added Ivermectin into a cellular culture infected with the virus on a petri dish. High concentrations of Ivermectin were shown to reduce viral replication in two cultures by 50% and 99%.

While promising, so-called in vitro — petri dish, in other words — or animal experiments often offer positive results that aren’t replicated in human subjects. The depth or extent of adverse effects on humans are also not foreseeable through cell cultures. This is commonplace in drug development cycles.

What’s more, the concentrations of Ivermectin deployed by Caly et al are far higher than we could prescribe to humans. This has led some doctors to be sceptical that Ivermectin could work as claimed, simply because the amounts in patients systems is far lower than in the in vitro study. The maximum concentration achievable in the blood after a standard oral dose of Ivermectin (200 mcg/kg) is around 40 ng/ml. Yet the concentration in just the lower-concentration culture was around sixty times higher than this standard dose — and as we’ll see in later studies, even ten times higher than a high-dose study performed by Guzzo.

After the promising — if highly cautious — evidence of in vitro effectiveness, a number of human trials into Ivermectin have been commissioned. These sit on either end of observational evidence — drawn from observational trials, where patients are given the drug in a non-randomised manner and their conditions monitored — and randomised control trials (RCTs).

RCTs are the gold-standard of medical evidence, lying at the top of a so-called ‘evidence pyramid’, because they protect against bias. They’re studies in which a number of similar people are randomly assigned to two (or more) groups to test a drug. One group is given the active drug, while the other has an alternative intervention, such as a placebo drug or no intervention at all.

There have been sixty studies in total around Ivermectin. Thirty-nine have been peer-reviewed — a plus, given that peer review allows other members of the scientific community to appraise, critique and sense-check the results — and 30 have been RCTs, with sixteen of those on ‘early treatment’, three on prophylaxis, and eleven on late-treatment.

Prophylaxis (prevention)

One of the most consequential claims about Ivermectin is not related to treatment, but to prophylaxis, or that it works as a prevention to contracting Covid-19. It’s a simple fact, as noted above, that there are far fewer studies related to prevention compared to treatment. Bret Weinstein on numerous occasions has claimed that Ivermectin is “something like 100% effective” at preventing Covid, and suggest that people could take it in lieu of vaccines. This “100% claim” rests on one study, an observational study conducted in Argentina on healthcare workers by Hector Carvallo.

Carvallo et al

Let’s consider thestudy by Carvallo et al in Argentina, which has been referenced by a number of Ivermectin’s proponents. These include Bret Weinstein and Heather Heying, who use the study to ground their claim that Ivermectin is “something like 100% effective in preventing infection by COVID-19, if used properly.” Bret Weinstein and Dr Pierre Kory also likely used the striking result of Carvallo et al to anchor a suggestion, made on The Joe Rogan Experience podcast, that Ivermectin could eradicate our pandemic.

The study is an observational trial that investigates the facility of Ivermectin (together with another drug, the plant-derived iota-carrageenan) as a prophylactic against COVID-19.They gave healthy volunteers Ivermectin and carrageenan daily for 28 days and matched them to similarly healthy controls who did not take the medicines.

Of the 229 study subjects, 131 were treated with 0.2 mg of Ivermectin drops taken by mouth 5 times per day. After 28 days, none of those receiving Ivermectin in the prophylaxis group had tested positive for SARS-COV-2 versus 11.2% of patients in the control arm. In a much larger follow-up prospective, observational controlled trial by the same group that included 1195 health care workers, they found that over a 3-month period there were no infections recorded among the 788 workers who took weekly Ivermectin prophylaxis, whereas 58% of the 407 controls had become ill with COVID-19.

These are promising results — described by Pierre Korry of the FCCC as a “remarkable protection against transmission” — but some have been critical. Yuri Deigin of the DRASTIC Group — the decentralised research collective that first sounded the alarm over a lab leak — has pointed out that this study is not a straightforward study of Ivermectin, but rather of the drug combined with another in iota-carrageenan. This means it’s hard to isolate the material effect of Ivermectin.

In an explainer video, Dr Carvallo said that iota-carrageenan acts as an “enhancer” molecule to the Ivermectin by wrapping around the virus through the effects of polarity. This was taken by one decentralised (not peer reviewed/published) meta-analysis to mean that iota-carrageenan is not technically necessary, and the trial should be read as a function broadly of Ivermectin alone.

In his explainer video, Dr Carvallo also explains that around one-sixth of those admitted to hospital for COVID-19 were medical personnel. This matched roughly the “background infection rate” described in his study, which was 20% of hospital personnel. Deigin has pointed out, though, that the study contains some large variances that make little sense if the study was conducted in truly unbiased conditions: in one hospital included in the study (out of four in total), 0% of those receiving the treatment were infected, while 92% of those in the control group were infected. This is several factors out of the background in both directions.

One can point out issues with the study design more generally. Being an observational trial, this is not the ‘gold standard’ of evidence requisite to draw firm conclusions about Ivermectin’s efficacy. That Bret Weinstein and Heather Heying in particular drew a “near 100%” effectiveness conclusion — and supplemented this with taking Ivermectin live on air — has therefore drawn heavy criticism from many onlookers, including Deigin and journalist Claire Berlinski in an article for Quillette and a piece by Matt Johnson in Arc Digital.

The number of patients in the control and active groups is also not matched — nearly double the sample size were administered the active drug. This will not necessarily skew results in any one direction — it’d be more likely to dilute the effect of the Ivermectin combination, being that strong impacts would have a lesser proportionate impact. The samples were “controlled for age, demographics, past medical history, work environment including hours worked and possible exposure to COVID-19 positive patients within the hospital” according to the authors.

Most importantly, both Yuri Deigin and Dr Graham Walker (an emergency physician in San Francisco and member of the Evidence Base collective on Clubhouse, which appraises medical claims) has argued that the conclusions of the study — near-100% efficacy in the larger trial, 58% overall infection rate in the controls, and so on — are too striking to be accepted without a grain of salt.

According to Walker, it’s unheard of for studies to draw near-perfect results. There will always be variation in the ‘experiment of nature’, including the differences of genetic makeup, hospital and home conditions — they can never be equalised totally — and sheer human error, such as people forgetting to take their tablets at some point in the three months of the study. Even Tess Lawrie, one of Ivermectin’s strongest advocates, conceded in conversation with Rebel Wisdom that she understood why people were sceptical of any claim that any drug was “100% effective”.

The Carvallo study also deviates strongly from the broader evidence base around Ivermectin as a prophylactic. The British Medical Journal’s appraisal found the evidence was “very uncertain”, while epidemiologist Dr. Gideon Meyerowitz-Katz has called the evidence base broadly scant on prevention, or at least compared to that studying treatment post-infection.

Gideon Meyerowitz-Katz has just done a deep dive into the methodology and data in the Carvallo paper, and has argued that there are serious concerns about its conclusions and methodology.

It is early days, and difficult to verify, but there are also news reports starting to emerge of infections in people taking Ivermectin as a prophylactic, such as this story from South Africa:

“A leading pulmonologist has issued a stark warning that all the patients now admitted to his clinic thought ivermectin would protect them from contracting Covid-19.

In a chilling Facebook post, Dr Emmanuel Taban, a pulmonologist at Mediclinic Midstream in Midrand, wrote that two out of every three patients now being admitted to the hospital were taking ivermectin which, he added, offered “no benefit at all”.

The bigger picture

Let’s zoom out to the other forms of evidence around Ivermectin. There have been a number of meta-analyses of different studies around the drug. Meta-analyses group together randomised control trials (RCTs), observational control trials (OCTs), and other forms of study to give an aggregated take on the evidence, with some excluded depending on protocols to reduce bias. Meta-analyses can be of varying quality: scientists use tools known as ‘funnel plots’, which situate studies on a graph where their conclusions can be seen and compared against a baseline at the midpoint of the axis.

Funnel plots which are asymmetrical — strongly to the left or right of the baseline — are suspicious. They suggest that some form of ‘publication bias’ has set in, where studies are included on biased grounds. Funnel plots which are heterogeneous — where the distribution is all over the graph, with no central trend — are likely inconclusive, with the evidence base uncertain on a particular treatment’s effects.

In the following sections, we’ll use three key meta-analyses as a way into understanding the evidence around Ivermectin and the discussions of its evidence.

Bryant, Lawrie et al

A review by Bryant, Lawrie et al — note, Tess Lawrie of the BIRD Group, which we’ve mentioned above — considered 27 studies in Ivermectin’s action as a treatment, measured by reduction in symptoms and preventing death, and a prophylactic against COVID-19.

Some highlights of the meta-analysis include a pre-print from Bangladesh, which administered Ivermectin in combination with another therapeutic on patients with mild-to-moderate COVID-19: patients’ lungs, the authors report, were significantly improved, body temperatures stabilised, nd respiratory symptoms were alleviated, and all in just seven days.

Another study on the same combination therapy in Bangladesh found that viral clearance — how much a virus is removed before and after a therapeutic — was significantly improved in five days of administration. An RCT in India concluded that a “significantly higher number” of patients left hospitals alive when administered Ivermectin than control. Niaee et al found that Ivermectin “reduced the rate of mortality, low O2 duration, and duration of hospitalization” in an RCT of 180 patients.

“Overall, death from any cause, taking into account all composite analyses, was judged to provide moderate-certainty evidence”, the authors wrote. Moderating the deteriorating effects of the disease — e.g. the need for mechanical ventilation — was judged to be “low to very low certainty evidence”.

The authors concede in their discussion notes that “several of the studies contributing data did not provide full descriptions of methods, so assessing risk of bias was challenging.” Many of the original authors were contacted to supply further detail and their original data, but not all were responsive.

There was high “variability in the participants recruited, treatment regimen, and the care offered to those in control groups”, with an attempt made to account for this in the meta-analysis. Many of the studies were not peer-reviewed.

Some of the studies were also of low evidential quality — something Bryant, Lawrie et al concede, but which complicate any conclusions. A Canadian agency review concluded this meta-analysis was of “critically low quality”. For instance, of the Bangladeshi and Indian studies highlighted above, two were combination therapies — as with Carvallo et al — and on low sample sizes, and the final study mentioned actually found “no difference in the primary outcome i.e. negative RT-PCR status on day 6 of admission with the use of Ivermectin.” One paper cited in the meta-analysis, contrary to Lawrie’s later claim in a YouTube video explaining the meta-analysis, showed that Ivermectin is unlikely to be effective at treating patients with mild COVID-19.

A January study from Spain, too, found that patients receiving a single dose of Ivermectin within 72 hours of fever or cough onset saw no difference in the proportion of positive PCR tests.

The Petkov study, a double-blind RCT on Ivermectin with COVID-19-infected patients, was judged to be of “low bias” by the meta-analysis, but has been criticised for its lack of transparency. The Niaee et al study, likewise mentioned above, recruited people who were PCR negative for COVID-19 as well as those who tested positive, but final results showed that nearly 50% were PCR negative in the control group and only 20% negative in the intervention. In its analysis of Niaee et al, the WHO pointed out that the authors began “enrolling and randomizing patients prior to the protocol being publicly posted, another factor that contributes to an increased risk of bias.”

Crucially, the study includes three RCTs on Ivermectin’s facility as a prophylactic. A study cited both in this meta-analysis and a ‘Bayesian analysis’ by the University of Leicester, and by Dr Pierre Kory is Elgazaar et al, an RCT from Egypt. This found that patients with COVID-19 treated in hospital who “received Ivermectin early reported substantial recovery” and that there was “a substantial improvement and reduction in mortality rate in Ivermectin treated groups” by 90%.

Elgazaar et al had raised red flags to researchers for some time. It included “no information whatsoever on allocation concealment at all, and the two sentences on randomization procedures actually contradict each other”, according to epidemiologist Dr Gideon Meyerowitz-Katz. A further review by an independent researcher found that much of the data was duplicated and its introduction almost-entirely plagiarised, leading to its retraction from the pre-print server on “ethical concerns”.

The Elgazzar study was the biggest RCT, that found the biggest effect for Ivermectin. Gideon Meyerowitz-Katz claims that removing the Egyptian study from Tess Lawrie’s meta analysis should fundamentally change the conclusions, and means that there is now little proof that it works. He says “the benefit of Ivermectin decreases from 62% to 42%, with no clear benefit compared to placebo. In a simple to follow Twitter thread he argues that nearly all the benefit observed in Lawrie’s study now relies on one study from Iran that has been rated as very low quality, and should be excluded.

Tess Lawrie disputes this, and claims that her study still shows a significant benefit. We are not equipped to adjudicate these competing claims, but this should not be a difficult thing to do, if an independent third party tests the data and decides that Lawrie or Meyerowitz-Katz is correct.

Hill et al

Another academic who has been evaluating the data on Ivermectin is Andrew Hill of Liverpool University. His meta-analysis drew on twenty-four randomized clinical trials with 3,328 patients.

“In 11 randomized trials of moderate/severe infection, there was a 56% reduction in mortality compared to 9% of deaths in controls”, they concluded, with favorable clinical recovery and reduced hospitalization.”

Like Bryant, Lawrie et al, Hill et al draws on the Elgazaar et al study, which has prompted a call for re-analysis. The authors likewise concede that “many studies included were not peer reviewed and a wide range of doses were evaluated”, which would likely complicate results and reduce their certainty.

In communication with Hill, Rebel Wisdom was told that he agreed that the removal of the Elgazzar study made the picture much more uncertain, and said that he now believed that more data was needed to form any firm conclusions.

Roman et al

A recent meta-analysis concluded that, in comparison to control therapies, “Ivermectin did not reduce all-cause mortality, length of stay or viral clearance in RCTs in COVID-19 patients with mostly mild disease,” and that Ivermectin “is not a viable option to treat COVID-19 patients.” Roman et al considered ten RCTs with 1,173 patients, with one half of the studies controlled by placebo and the other by ‘standard of care’, which is the medical treatment that is normally provided to people with a given condition. Roman et al considered COVID-19 post-infection in a range of condition severity.

The study was advanced by Yuri Deigin and Claire Lehmann of Quillette as evidence of Ivermectin’s shortfalls as a therapeutic. Nevertheless, it drew sharp criticism from Ivermectin’s proponents, including from authors on Trial Site News.

The meta-analysis’ low sample size problematised their results, they claim, with Roman et al considering only eleven studies (although they report ten mistakenly) compared to Bryant, Lawrie et al’stwenty-four’ (although it was twenty-seven) and Hill et al’s eighteen (although it was twenty-four). Roman et al also did not consider Ivermectin’s facility in preventing mortality, which was a point of criticism raised in the WHO’s appraisal of the evidence base (considered below). The study also does not address Ivermectin’s facility as a prophylactic.

Roman et al’s strong conclusion — that Ivermectin “is not a viable option” — seems, according to the Trial Site News criticism, to support the case for no further study on Ivermectin with COVID-19. Yet such certainty and dismissal is not an attitude held, the authors point out, by the WHO, the University of Oxford (as with its major PRINCIPLE study into treatments for COVID-19), or major insurers like UnitedHealthcare.

Yet the WHO does not actively recommend further clinical study. They recommend, rather, that Ivermectin should be prescribed only within the context of “clinical trials” that may or may not occur. This aligns with the full conclusion of Roman et al, which is that “Ivermectin is not a viable option to treat COVID-19 patients, and only should be used within clinical trials context.”

The World Health Organisation

The WHO considered sixteen studies in its own analysis of Ivermectin. They excluded quasi-randomized trials, or any RCT that did not use explicit randomization techniques, which were otherwise included in Bryant, Lawrie et al’s meta-analysis. Of these RCTs, the WHO notes, “only five directly compared Ivermectin with standard of care and reported mortality”, two benchmarks for adequate controls in RCTs.

They deemed two of these RCTs, Kirti et al and Niaee et al (the Egyptian study considered earlier) to be inadequately blinded and at “high risk of bias”. Another of the five, the Gonzalez trial, considered Ivermectin in combination with hydroxychloroquine, another non-vaccine treatment, which renders isolating the effect of Ivermectin problematic. What’s more, the WHO has actively warned against the prescription of hydroxychloroquine, with a recent meta-analysis indicating that its use is associated with a higher risk of death than control.

The final study of the five, an RCT in Colombia, concluded that, “among adults with mild COVID-19, a 5-day course of Ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms.” Again, however, this does not undermine Ivermectin’s possible application in treating more severe, later-stage COVID-19 or in preventing infection. The Colombian trial is also just one mark along a spectrum of possible dosing and duration regimens, and the authors critically note that “larger studies” will be required to draw more meaningful conclusions around Ivermectin’s benefits.

Country data

Outside of observational studies and RCTs, many of Ivermectin’s proponents have pointed to the top-line analysis of national data. Countries and cities across South America, South Africa, Zimbabwe and India were early to adopt Ivermectin as a therapy against COVID-19, and drops in case numbers followed.

Kory describes it well:

“In Brazil, the cities of Itajai, Macapa, and Natal distributed massive amounts of Ivermectin doses to their city’s population, where in the case of Natal, 1 million doses were distributed.

“The distribution campaign of Itajai began in mid-July, in Natal they began on June 30th, and in Macapa, the capital city of Amapa and others nearby, they incorporated Ivermectin into their treatment protocols in late May after they were particularly hard hit in April. The data… show large decreases in case counts in the 3 cities soon after distribution began compared with their neighboring cities without such campaigns.”

Likewise, some Indian states, including Goa and Uttarakhand, adopted Ivermectin in April 2021 into their recommended therapy regimens and saw large drops in case counts soon afterwards.

Yet country-level analysis, while useful and indicative, is of markedly less value than observational trials and RCTs. It does not account for the mitigating effects of social distancing, mask wearing, indoor regulations, or even the role of other non-vaccine treatments that were administered simultaneously. Importantly, national or city analyses do not count precisely how many people have taken Ivermectin, often the make-up of the people who did — one can control by comparing one city to an adjacent and similar one, but the relevant population constitutions of the city can differ significantly — or how many died or where patients were situated on the infection cycle.

Some of the population evidence has been disputed in more specific ways. Peruvian studies suggest that one state, Lareto, saw sustained drops in COVID-19 cases before Ivermectin was ever-distributed, and deaths were only counted for those over sixty. The re-emergence of infections seems also to detract from Ivermectin’s prophylactic efficacy, and no data was compiled for Lima, the country’s capital. Crucially, five months on from unveiling the drug, the country’s health minister announced it and other unproven drugs wouldn’t be used on hospitalized patients anymore because of insufficient evidence, especially with a meta-analysis from Peruvian scientists which suggested no benefit for overall mortality.

It’s also worth noting that much of the South American embrace of Ivermectin was driven by an early study, Mehra et al, released shortly after the in vitro study of Caly et al. The study has since been retracted, however, since a core data source from the firm Surgisphere was fabricated, prompting a high-profile scandal.

To take India, Yuri Deigin has pointed out that dropping case numbers is not relevant, since Ivermectin is not administered as a prophylactic. And away from headlines suggesting Ivermectin’s blanket prescription, the drug is, rather, recommended as a possible treatment in mild cases of COVID-19. Any evidence for prophylaxis would be left wanting, too, Deigin argues, since Ivermectin prescriptions did not prevent the surge in COVID-19 cases and the emergence of the Delta variant — events that have produced enormous death counts not fully accounted for in government statistics, which further problematises the case for Ivermectin. This is the case especially for Goa and Uttarakhand, two states highlighted for their recent Ivermectin programmes, since they’ve respectively reported the second and fourth highest death ratios in India.

Conflicts of interest

The WHO’s analysis may be irrelevant to many of Ivermectin’s proponents, or even those unpersuaded by its evidence. The WHO has come under significant scrutiny throughout the pandemic for its conflicts of interest and several systematic errors in managing the viral spread. The WHO has been accused of corruption, a cosy relationship with the Chinese Communist Party, and for facilitating a cover-up over the ‘lab leak’ (covered in Rebel Wisdom’s briefing book on the hypothesis). The WHO was criticised in the early pandemic stages for dismissing the role of aerosol transmission — something pointed out early by Bret Weinstein and Heather Heying of The Dark Horse — the efficacy of masks, or the virus’ status as a pandemic altogether.

These criticisms can be applied to the FDA, the CDC and the NIH, all of which have both failed to endorse Ivermectin and been accused of long running conflicts of interest and institutional capture. Indeed, as argued in Dr Ben Goldacre’s Bad Pharma and elsewhere, the pharmaceutical sector is prone to corruption and skewed results. One can reasonably agree with Weinstein’s conclusion, then, that we should “expect deception” in the public-facing results of various therapies in relation to COVID-19.

In particular, several Ivermectin proponents claim that institutions and corporate forces are reluctant to endorse the drug or sanction further research for commercial reasons. Ivermectin is cheap, easily-manufactured, and crucially out-of-patent, which means that no large pharmaceutical firms can privatise their earnings from the drug: a strong contrast to the vaccines, from whose “adverse events” of side effects and any associated litigation the firms are immune, as per agreements with national governments.

Others argue that the commercial case is for Ivermectin, rather than against it. For instance, with all the press and scientific attention directed towards the drug, its prices have risen substantially in recent weeks. While commercial pressures from big pharma in the US could explain why off label alternatives have been systematically ignored or downplayed, the commercial pressures point in the other direction for health services around the world. There is a huge incentive for, say, the Indian health service, or the NHS, or other developing countries, to identify and use cheap and available medications in lieu of expensive and hard to source vaccines.

As Graham Walker points out in our film, patent and intellectual property concerns have also not dissuaded pharmaceutical firms from selling and distributing Dexamethasone, another cheap treatment that’s being prescribed around the world.

The WHO has also not been reluctant to endorse non-vaccine treatments. The WHO strongly recommended the use of corticosteroids in a recent ruling. The WHO has faced reasonable charges of capture, too, but treating Ivermectin’s critics and detractors under a single brush — as with Kory’s designation of the “narrative” in favour of vaccines, and against small-molecule treatments — is likely to be problematic. The boundaries of such a coalition would be sizable, and it’s not guaranteed that their interests would always align — and it’s not clear how scientists and epidemiologists critical of Ivermectin fit in the picture. There is no payment for error detection in science, for example — and the whole field is systematically under-funded compared to research and finding novel results.

Pharmaceutical business models need not rely solely on high prices and clear property rights over compounds, either. On the other end of the spectrum, large profits can be generated through high volume at low margins — and being that Ivermectin is repeat-prescription, frequently-consumed, and targeted at everyone throughout the infection cycle, there is a very sizable market to capture in selling the drug.

It’s also of interest that Ivermectin’s manufacturer, Merck, has not endorsed the drug. Merck also did not license the drug to Japanese scientists at the pandemic’s origin.

Yet critics on Trial Site News have pointed out several reasons why this may be. Merck is a signatory of the Mectizan Donation Program, which binds manufacturers to give Ivermectin away for free in treating river blindness. A quick rejoinder is that Ivermectin is known as a highly-effective treatment for river blindness, a parasitic infection, while the drug’s usefulness against COVID-19 is not established — yet river blindness’ severity and spread, especially across the developing world, underwrites the need for free distribution, and COVID-19’s highly-destructive and global spread is several-fold more severe than river blindness, and may create an even stronger case for a lack of paywall.

More importantly, despite being the drug’s manufacturer, Ivermectin is still off-patent, and several manufacturers would likely enter the market at lower cost. Prioritising Ivermectin may cannibalise the firm’s resources for other, more profitable drugs, including COVID-19 treatments like MK-7110 and Molnupiravir, with which it has a $1.2B agreement with the US government. Prioritising low-cost, high-volume distribution, while feasible, may be categorically less favourable than higher-margin strategies for some shareholders, too.

Why not just use Ivermectin?

While Ivermectin’s evidence base may be uncertain, the drug has been known about since 1975, and its risk profile is low and well-understood. That the drug may show some promise may be enough to ground its prescription, especially in the emerging world where billions remain unvaccinated and in need of cheap therapeutics.

Some, like Dr Graham Walker, have raised concerns that Ivermectin may drive vaccine hesitancy, especially since some of Ivermectin’s proponents — Bret Weinstein and Heather Heying, Dr. Tess Lawrie — are sceptical of the vaccines. A feeling of security from Ivermectin may produce less caution around social distancing and mask wearing.

While the vaccines are a newer form of medical treatment than Ivermectin — with some persuaded that the vaccines’ potential for long-term risks are not worth taking — even the most optimistic estimates of Ivermectin’s prophylactic capacity (85%, overlooking any biasing or lack of controlling in their studies) are lower than the vaccines, whose prevention ratio is around 90%. Put another way, this would mean your odds of developing COVID-19 while taking Ivermectin are about 6.67 times lower than control. Yet if you’ve received an mRNA vaccine, however, your odds are 20 times lower. Ivermectin’s need for repeat prescription, versus the vaccines’ discrete one-, two- (or three-) shot ‘and you’re done’ approach is likely also to reduce human error.

What’s more, there is little evidence of the drug’s effects in COVID-19 patients prone to inflammation. These pro-inflammatory states may increase the penetration of Ivermectin into the central nervous system with unknown consequences. Other potential issues include drug-drug interactions with some antivirals given to COVID-19 patients such as ritonavir which may increase the levels of Ivermectin.

Ivermectin is widely available as a veterinary drug, too. It’s possible, some warn, veterinary doses may be used at scale and in unsupervised ways that risk overdose — consider, for example, how some internet users are contemplating horse formulations, prompting a warning from the FDA. More than 5,000 indigenous Peruvians were even injected with veterinary Ivermectin by a medical group.


Congratulations on having made it to the end — I’ll repeat what we said at the outset, to be aware that this document is incomplete, and barely touches on the deeper forces at play, which is awesomely powerful narratives competing with each other.

First principles thinking and valuing heterodoxy is not the same as reactive contrarianism for its own sake. First principles thinking can lead you to accepting the ‘consensus’ position as well as the contrarian, by following the data and the logic to its natural conclusion.

“We have to be fully aware of our innate tendency to be captured, by hijacking by powerful narratives on either side. And to also use that awareness to evaluate any truth claims made by others. This is why Rebel Wisdom has always made it a priority to be self critical and aware of our own biases, and to be suspicious of anyone motivated by excessive levels of certainty and evangelical zeal. Humility is needed.”

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Ivermectin — For and Against, Briefing Document was originally published in Rebel Wisdom on Medium, where people are continuing the conversation by highlighting and responding to this story.

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