Ivermectin is the new hydroxychloroquine, take 3: Conspiracy theories and grift

After last Friday’s post, I hadn’t planned on writing about ivermectin again for a while. Ivermectin, as you might recall, is the veterinary deworming drug also sometimes used in humans to treat various parasitic worms, that has become the new hydroxychloroquine in that, despite an extreme paucity of clinical evidence, has taken hydroxychloroquine’s place as the new “miracle cure” (or at least highly effective) treatment for COVID-19 that “They” don’t want you to know about (because, of course, it’s off patent and cheap and would thus eliminate the need for COVID-19 vaccines). Although ivermectin is not quite there yet, it’s fast approaching the point in its predecessor’s saga nearly a year ago when I labeled hydroxychloroquine the Black Knight of COVID-19 treatments, in a nod to Monty Python and the Holy Grail‘s Black Knight who hilariously refused to admit defeat no matter how many of his limbs King Arthur lopped off.

The first time I discussed ivermectin, I described how poor the evidence for ivermectin’s efficacy against COVID-19 is; the second time, I started to discuss the conspiracy theories being peddled by the crank physician group Frontline COVID-19 Critical Care Alliance (FLCCC), the UK ivermectin advocacy group BIRD, evolutionary biologist turned right wing conspiracy theorist Bret Weinstein, and, of course, über-quack Joe Mercola. Since then, however, I’ve become aware of more negative evidence against ivermectin, which I will discuss, as well as some reporting that led me to wonder just what is behind this push for ivermectin, which is arising mostly from right wing sources, the “Intellectual Dark Web,” and other antimask and antivaccine conspiracy sources.

A randomized clinical trial and a meta-analysis of ivermectin

Last Friday, BMC Infectious Disease published a clinical trial of ivermectin by investigators in Argentina to prevent hospitalizations in patients with COVID-19. . The study describes the results of IVERCOR-COVID19, a randomized, double-blind, placebo-controlled clinical trial. It’s a decent-sized randomized controlled study, 501 patients, in which ivermectin was tested for its ability to prevent hospitalization in patients diagnosed with COVID-19. Patients were randomized to either the ivermectin (N = 250) or placebo (N = 251) arms using a staggered dose of the drug, according to the patient’s weight, for two days. The trial was carried out from August 19, 2020 and February 22, 2021 in the province of Corrientes, Argentina by the Ministry of Public Health of the Province of Corrientes in coordination with the Corrientes Institute of Cardiology “Juana F. Cabral”. Patients over 18 years of age residing in the province at the time of diagnosis of COVID-19 by PCR for SARS-CoV-2 within the last 48 hours before enrollment were eligible. Exclusion criteria included current home oxygen use or hospitalization at the time of diagnosis; history of COVID-19 hospitalization; breastfeeding women; known allergy to ivermectin; presence of mal-absorptive syndrome; presence of any other concomitant acute infectious disease; known history of liver disease; need for dialysis; concomitant use of hydroxychloroquine or chloroquine; or use of ivermectin up to seven days before randomization.

Let’s just say that the results were…disappointing:

In the IVERCORCOVID19 trial, in patients with a positive COVID-19 nasal swab by RT-PCR technique in the last 48 h, ivermectin in a staggered dose according to the patient’s weight for 2 days had no significant effect on preventing hospitalization of patients with COVID-19. No significant differences were observed in secondary outcomes such as the time elapsed from study enrollment to hospitalization in those who required it. Additionally, no significant differences were observed in the use of invasive mechanical ventilatory support, the requirement for dialysis, negative nasal swabs at 3 and 12 days after study enrollment, or in all-cause mortality. Patients who received ivermectin required invasive mechanical ventilatory support earlier. The use of ivermectin was not associated with increased adverse events.

So the best thing you can say about the results of this trial is that ivermectin appears to be safe in that its use wasn’t associated with an increase in adverse events. As far as the primary endpoint, there was no difference in the need for hospitalization between placebo and control groups. (It is here where the double-blinding is critically important, because if the doctor or subject knew which group the subject was in, it might have unconsciously influenced the decision of the doctor whether or not to admit a subject to the hospital for COVID-19 symptoms.) Similarly, there was no significant difference in mortality detected. In fairness, though, the trial was not designed or powered to find a difference in this secondary endpoint. As for the increased need for mechanical ventilatory support in the ivermectin group, given the relatively small number of events, this could easily have been due to random chance because the total number of patients who required mechanical ventilation in the study was small.

Also, in fairness, this study had another problem. Specifically, there was a lower rate of hospitalizations than expected. Moreover in the power calculations, the investigators were—shall we say?—overly optimistic in their assumptions. Basically, they assumed a high rate of efficacy for ivermectin, specifically an odds ratio of 0.3 to 0.5, which would translate into an estimated 50-70% reduction in the rate of hospitalization in the ivermectin group compared to placebo. This means that one must concede that this trial can’t rule out some efficacy for ivermectin less than a 50-70% reduction in hospitalizations. This study is, however, yet another in the drip-drip-drip of negative studies of ivermectin that is becoming very reminiscent of the drip-drip-drip of negative studies for hydroxychloroquine a year ago.

This brings me to a new meta-analysis published last week. I hadn’t been aware of it when I wrote my post. Published in Clinical Infectious Diseases, the official journal of the Infectious Diseases Society of America, this meta-analysis was carried out by investigators from the US, Peru, and Brazil.

In brief, the investigators searched for published and preprint randomized controlled trials (RCTs) assessing ivermectin effects on COVID-19 adult patients were searched through March 22, 2021 using five search engines. The primary outcomes examined were all-cause mortality, length of stay (LOS), and adverse events (AE). Secondary outcomes examined included viral clearance and severe AEs. Risk of bias (RoB) was evaluated using Cochrane RoB 2·0 tool. Inverse variance random effect meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methodology.

As with the clinical trial I mentioned, the results were…less than impressive:

Ten RCTs (n=1173) were included. Controls were standard of care [SOC] in five RCTs and placebo in five RCTs. COVID-19 disease severity was mild in 8 RCTs, moderate in one RCT, and mild and moderate in one RCT. IVM did not reduce all-cause mortality vs. controls (RR 0.37, 95%CI 0.12 to 1.13, very low QoE) or LOS vs. controls (MD 0.72 days, 95%CI −0.86 to 2.29, very low QoE). AEs, severe AE and viral clearance were similar between IVM and controls (all outcomes: low QoE). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality in three RCTs at high RoB was reduced with IVM.

Notice that last sentence. The RCTs with high risk of bias demonstrated significant reductions in all-cause mortality in patients suffering from COVID-19. In any case, contrary to the findings of Lawrie’s meta-analysis, there weren’t really any good high quality trials. I also note that these authors didn’t include one of the studies (Elgazzar 2020) that Meyerowitz-Katz described as having “no information whatsoever on allocation concealment at all, and the two sentences on randomization procedures actually contradict each other, yet it is still rated as ‘low risk of bias’ for both of these fields”. It’s also one of the studies that, when removed from Lawrie’s meta-analysis, resulted in a positive meta-analysis becoming negative. As far as the other, Niaee 2020: this newer meta-analysis rates this study as having a high risk of bias—appropriately so, in my opinion. Lawrie’s inclusion of Elgazzar et al and erroneous rating of Niaee et al just show the principle of “garbage in, garbage out” in meta-analyses. It also shows how, when the overall quality of the studies included is low, even one or two outliers of poor quality can change a negative meta-analysis to a falsely positive one.

Finally, this meta-analysis concludes:

In conclusion, in comparison to SOC or placebo, IVM did not reduce all-cause mortality, length of stay, respiratory viral clearance, adverse events and serious adverse events in RCTs of patients with mild to moderate COVID-19. We did not find data about IVM effects on clinical improvement and need for mechanical ventilation. Additional ongoing RCTs should be completed in order to update our analyses. In the meanwhile, IVM is not a viable option to treat COVID-19 patients, and only should be used within clinical trials context.

Before I move on to more of the ivermectin conspiracy theorists and potential reasons for them, I can’t help but repeat what I’ve been saying all along about ivermectin. Combining preclinical studies that show antiviral activity against SARS-C0V-2, the coronavirus that causes COVID-19 in vitro (cell culture) but only at much higher concentrations of ivermectin than can be achieved with safe doses in the bloodstream with the equivocal clinical trial results lead to a conclusion that this drug almost certainly does not work to treat COVID-19. This is particularly likely given that the highest quality existing randomized controlled clinical trials of ivermectin are all basically negative.

I note that when I discussed how poor the evidence for hydroxychloroquine for COVID-19 was, I routinely received criticism that I “wanted patients to die” and was “hoping” that the drug didn’t work. I’m getting some of the same nonsense now that I’ve finally been prodded to write about ivermectin. Nothing could be further from the truth. Even though, now that there are safe and effective COVID-19 vaccines, the need for a cheap and effective drug that can treat COVID-19 is not as desperate as it was a year ago, it is still acute given how large swaths of the globe still do not have access to the vaccines. Moreover, now that Oxford University has added ivermectin to the protocol of its massive PRINCIPLE Trial of treatments for COVID-19, it is possible that there might turn out to be a benefit due to ivermectin in treating COVID-19, clearly just not as massive as claimed by advocates and conspiracy theorists. I’d be just fine with that, as I would have been overjoyed if hydroxychloroquine had been shown to be as effective as its advocates had claimed it was. It’s just that, right now, the evidence is trending strongly in favor of the conclusion that ivermectin, like hydroxychloroquine before it, doesn’t work against COVID-19 in humans.

Not that any of that has stopped the conspiracies.

Grift and the disinformation war

As I’ve written before, I’m getting strong echoes from ivermectin advocates of the same sort of astroturf disinformation war that I got from advocates of hydroxychloroquine a year ago, only stronger. Why stronger? To be honest, I don’t know. It could be because many of the same people who promote ivermectin used to promote hydroxychloroquine back in the day last year and have gotten more skilled at spreading their message. It could be because the evidence for ivermectin’s efficacy against COVID-19 is not (yet) as overwhelmingly negative as it was for hydroxychloroquine. Who knows? What I do know is that this is an organized campaign, and reading two articles cemented that impression. One article is by the ever-perceptive Anna Merlan, who argues writing in VICE that the ivermectin advocates’ war has just begun. The other was published in the Houston Press by Jef Rouner, who points out the real dangers in the false COVID remedy promoters like Bret Weinstein.

Both are depressing reads. Merlan’s article is depressing (to me, at least) mainly for its contrast with hydroxychloroquine because, after clinical trials turned resoundingly negative for hydroxychloroquine, the more mainstream promoters of the drug backed off, leaving just the hard core conspiracy theorists still pushing it. (Indeed, not even the FLCCC promotes hydroxychloroquine now.) Yet the promotion of ivermectin continues apace, using a narrative in which proponents of the drug are being “silenced,” much as antivaxxers now claim they are being “silenced.” (Unsurprisingly, many—but, in fairness, not all—ivermectin advocates are also antivaccine.) For example, get a load of the story of Ivory Hecker, a former local TV reporter who was fired and accused her ex-employers of “muzzling her for not letting her cover Bitcoin and hydroxychloroquine.” Now, she’s all-in for ivermectin:

The coverage extended also to ivermectin, Hecker claimed, the anti-parasitic drug that several fringe doctors and less-fringe media personalities are claiming is a miracle preventative and cure for COVID-19. That claim has now led Hecker, post-firing, into the company of a new set of friends: the Front-Line Critical Care COVID-19 Alliance (FLCCC), a group of ivermectin-promoting doctors and their allies. On a weekly conference call, which was free and open to the public, Drs. Pierre Kory and Joseph Varon, two of the FLCCC’s founders, lightly interviewed Hecker and heavily implied that all three of them are under the same oppressive thumb of censorship, being silenced by the forces of media, Big Pharma, and their unnamed co-conspirators. 

“I’ve left two jobs” in medicine, Kory said, shortly after Hecker declared her gratitude that she’s not in jail for her beliefs. “I was attacked and harassed by two different employers and I left.” What was happening to all of them, he said, was a signal of how oppressive the public sphere has become for people who speak out: “In a certain sense, I’d like to believe it’s gotten so absurd that we now have to pay attention and do something and fix it. This can’t go on.”

I’ve discussed Pierre Kory before, of course. He’s one of the founders of FLCCC and has been flogging ivermectin conspiracy theories since last fall at least. But let’s see where the conspiracy theories lead us. Unsurprisingly, it includes claims that, because of government, medical, media, and (of course!) big tech’s “suppression” of discussions of how great ivermectin is for COVID-19, lots and lots of people have died unnecessarily. How many? Well…:

Ivermectin advocates believe themselves to be fighting against the forces of censorship to promote a suppressed cure for COVID-19. (Asked during a question and answer session how many people had been killed by social media censorship against ivermectin, Kory and Varon offered estimates in the six figures.) Despite the fact that the drug’s effectiveness at treating any kind of viral infection is far from clear, their holy war has taken on new vigor over the past several weeks, as prominent members of the so-called “Intellectual Dark Web” have begun advocating for the drug—and have found themselves running afoul of policies meant to prevent platforms being used for the advocacy of unproven medical claims.

Even worse, the conspiracy theories and claims of “suppression” are money-makers:

Their claims of suppression are also making ivermectin’s biggest promoters ever more famous. Kory announced this week that he’ll be following up on his appearance on Joe Rogan’s podcast, where he preached the gospel of ivermectin to millions, with an appearance on Dr. Drew. But on their weekly Zoom call, Varon and Kory agreed with Hecker, the fired reporter they were interviewing, that something truly sinister was taking place. Kory hinted at a new theory that may begin to take shape in the ivermectin sphere, asserting that something called the “Trusted News Initiative” may be to blame for ivermectin’s lukewarm reputation in the mainstream media. 

“A large part of the major mass media have made a decision that they’ll only allow discussion on what’s determined to be correct and efficacious by the WHO and the NIH,” he said. That decision seemed be linked, he implied, to the Trusted News Initiative, an project begun in 2019 involving a group of news organizations trying to agree on new standards and technologies to combat disinformation, most recently around elections and vaccines, and to provide continuing education resources to help journalists learn how to identify things like manipulated images.

In other words, predictably, the conspiracy theory is…evolving. It’s becoming wider, in order to become a broader conspiracy theory that portrays efforts by journalists and the mass media to combat disinformation and help journalists identify manipulated images and real “fake news” (news that is fake, compared to real news that politicians call “fake news” because it’s a threat) as a threat to whatever the conspiracy theorists believe in.

But let’s discuss the grift, because, associated with any conspiracy, there is always grift. Always. Jef Rouner makes this point even more forcefully than Merlan by making a comparison that is so spot-on that I really which that I had thought of it first:

Two months ago, I implored people to get vaccinated against COVID instead of taking horse dewormer, and my email has been a circus train of screwballs ever since. By far, the largest number of messages I get implore me to seek out the work of Bret Weinstein, a “professor in exile” and podcaster. I did just that, and I now believe the world is now in the beginning stages of Andrew Wakefield 2.0. Get a snack because it’s going to take us a while to get there. 

Wakefield was a British doctor. I mean was as in “no longer allowed to be a doctor” for reasons that will soon be abundantly clear. In 1998, he launched the modern anti-vaccination movement by claiming that there was a link between autism in children and the MMR vaccine when he published a study in the prestigious journal Lancet. His work spread like wildfire, leading to multiple measles outbreaks all over the world including Texas. The disease was declared extinct in the United States in 2000, but he managed to bring it back to horrific results like the world’s worst version of Jurassic Park.

By George, I think he’s got it! Weinstein and his fellow dewormer advocates are the modern incarnation of Andrew Wakefield. They promote ivermectin not just because they think it works, but because it is very profitable to their brand to do so.

I’ve written about Andrew Wakefield more times than I can remember, and regular readers will be familiar with his story, including how investigative journalist Brian Deer showed how Wakefield had committed scientific fraud in his Lancet case series; how he then became the patron saint of antivaccine conspiracy theorists, first of the “MMR causes autism” variety, the more generally; how as a result he lost his medical license in the UK or was “struck off,” to use the delightful British term for it; and how he’d done it all for money, a barrister named Richard Barr having paid him to produce evidence to use in lawsuits against vaccine manufacturers for “vaccine-induced autism” even as he had developed a measles-only vaccine that he hoped could compete against the MMR. Unsurprisingly, in the era of the COVID-19 pandemic, in addition to his antivaccine grifting Wakefield has glommed onto the antimask, anti-“lockdown” movement, apparently seeing a rich source of new marks as he parrots COVID-19 conspiracy theories and antivaccine nonsense adapted to the pandemic. It turns out that his fellow grifters have even co-opted Wakefield’s ideas to argue that COVID-19 vaccines will cause a mass extinction, possibly even of humanity.

Now comes the kicker:

Bret Weinstein is, simply, a right-wing media grifter in the vein of conservative political commentator Ben Shapiro and Canadian professor of psychology Dr. Jordan Peterson. Part of the “intellectual dark web,” (a term his brother Eric coined), Weinstein has risen in prominence over the last year as other members of the IDW have lost relevance. 

Weinstein made his reactionary right wing guru bones after he left his evolutionary biologist teaching gig at Evergreen State College in Washington State. He spoke out against the college’s traditional “day of absence,” where minority students and faculty would absent themselves to show their contribution to the college. A proposed change to the program would have asked white students to stay away instead to attend a program on race issues. Weinstein called this oppression. After a confrontation with protestors, Weinstein and Heather Heying, a fellow biology professor and Weinstein’s wife, sued the college. 

The couple resigned, and Weinstein began his career playing a skeptical maverick who was cast out by political correctness. His DarkHorse podcast is wildly popular, reaching Number 51 on the Podcast Insights chart. Weinstein, like a lot of IDW personalities, positions himself as a centrist intellectual just searching for answers, but it’s a thin veneer that is destroyed by even a cursory listen or look at his Twitter feed.

Here’s where Weinstein latches on to the “big Wakefield energy”:

Weinstein is also a fervent believer in ivermectin (that horse dewormer I mentioned above) as a cure for COVID, which is one of the reason he keeps having social media posts taken down for spreading misinformation. While it’s hard to find specific instances of him being overtly anti-vaccination, his latest output is implicitly such. In addition to insinuating there is a wide conspiracy to suppress ivermectin, he has had Dr. Geert Vanden Bossche on as a guest. This is where the big Wakefield energy comes in.

Here’s where I point out that I was comparing Vanden Bossche to Wakefield back in March. I just wish I’d thought of the term “big Wakefield energy.” I guess “Wakefield grift” will have to do. In any event, Bossche really is a lot like Wakefield, as Rouner points out:

It’s not hard to connect the dots. A seemingly prestigious scientist who is a lot less impressive when looked at with a critical eye begins crying doom about the current state of vaccination. Rather doing publishing research, he takes to Twitter and YouTube to get his message out, the hallmark of all great science. As an alternative, he offers a new path forward using technology that he is personally working on and stands to profit from. I suppose we should be grateful that Vanden Boscche isn’t teaming up with a disgraced quack who thinks his bone marrow cures autism like Wakefield did. At least, not that we know of.

Give it time, Mr. Rouner. Give it time (that is, if it hasn’t happened already).

Rouner concludes by pointing out—correctly—that at its heart this is all a con game. I prefer to refer to it as grift, because that’s what’s happening. Like Wakefield before him, Vanden Bossche is a once somewhat respectable scientists who has become so enamored of his own alternative vaccine strategy for COVID-19 that he’s spread a conspiracy theory about how existing COVID-19 vaccines are a threat to humanity. The result? Profit! Then Weinstein latched onto Vanden Bossche, seeing the potential to buff his conspiracy cred and thereby profit himself.

It’s likely the same reason that Weinstein has also latched on to ivermectin, as Merlan describes:

One prominent ivermectin advocate is Bret Weinstein. A former evolutionary biology professor turned podcast host and passionate promoter of ivermectin, he has appeared on Joe Rogan’s podcast with Kory to discuss the drug, which he and wife/co-host Heather Heying have repeatedly claimed on their podcast can prevent or treat COVID-19. Recently, after receiving “strikes” from Youtube, the couple moved their podcast to the fringe platform Odysee and put their claims about the suppression of science at the center of discussion, alongside speculation about whether powerful institutions want the pandemic to continue. Prominent media figures have rallied around them in support, a cast of characters ranging from Ben Shapiro to Matt Taibbi to Bill Maher to Rod Dreher to Bari Weiss to Glenn Greenwald, citing them as victims of either Big Tech censorship or else what Shapiro called the “increasingly censorious Left.”

Because of course any criticism of bad science, pseudoscience, and conspiracy theories coupled with attempts to slow the rapid spread of such disinformation must be “censorship” or “suppression.” This is nothing more than the longstanding tactic by conspiracy theorists and pseudoscientists to cast criticism as “suppression” and tyranny, leading to what Merlan describes thusly:

In reality, two parallel and increasingly divergent conversations are taking place around ivermectin. One involves the routine workings of science. The other, holding that social media platforms are engaged in censorship, suppression of free speech, or even perhaps a sinister conspiracy, has only gotten louder in recent days. That’s been aided by media personalities like Weinstein and Heying and their supporters as well as the FLCCC. Joyce Kamen, the group’s “VP of Public Information,” wrote a deeply conspiratorial blog post on Medium claiming that ivermectin is being suppressed by a vast global cabal, titled “The Bigge$t Lie, Perhaps Ever.” (Kamen, for her part, is not a doctor; according to her LinkedIn page, she studied journalism and worked as a broadcast producer in the 1980s, and now works on communications for nonprofit organizations.) 

And:

Their claims of suppression are also making ivermectin’s biggest promoters ever more famous. Kory announced this week that he’ll be following up on his appearance on Joe Rogan’s podcast, where he preached the gospel of ivermectin to millions, with an appearance on Dr. Drew. But on their weekly Zoom call, Varon and Kory agreed with Hecker, the fired reporter they were interviewing, that something truly sinister was taking place. Kory hinted at a new theory that may begin to take shape in the ivermectin sphere, asserting that something called the “Trusted News Initiative” may be to blame for ivermectin’s lukewarm reputation in the mainstream media. 

As I said at the beginning, all conspiracy theories are associated with grift. The grift might not be what gets them started, but it is definitely a prominent component of any conspiracy theory as it matures. Moreover, as I pointed out before, science denial is a form of conspiracy theory. It has to be, because believers need an explanation why “mainstream science” and “mainstream media” reject their conspiracy theory. Naturally, it has to be a tyrannical conspiracy to “suppress” their ideas.

Ivermectin as a “cure” (or at least a highly effective treatment) for COVID-19 is basically science denial. It is still possible that science will show ivermectin to be effective against COVID-19, but from my perspective that outcome is looking less and less likely. Thus, not surprisingly, the promotion of ivermectin requires denying the inconvenient science, with all the techniques of denial used by denialists ranging from creationists, to antivaxxers, to cancer quacks, to climate science deniers being marshaled against disconfirming science. Because all science denial includes a conspiracy theory, we should therefore not be surprised that ivermectin advocates have not only embraced conspiracy theories about the “suppression” of their favored COVID-19 cure, but have gone beyond that to go even bigger on the conspiracy mongering to portray any effort to combat disinformation as a grand conspiracy to suppress The Truth about…everything.