Ivermectin for Covid-19: abundance of hype, dearth of evidence

Here’s a tip for navigating the constantly evolving data on treatments for Covid-19: Beware when someone describes a drug as a “miracle.”

The ongoing devastation wrought by the Covid-19 pandemic creates an understandable allure for a quick-fix or magic-bullet solutions. But it is painstaking scientific testing — not magical thinking — that reveals what works and how well. For example, clinical trials involving tens of thousands of patients across multiple continents were needed to demonstrate the enormous value of Covid-19 vaccines.

In the early months of the pandemic, hydroxychloroquine was touted by President Trump, even in the absence of adequate supporting data. Today it’s the antiparasitic drug ivermectin, whose developers were awarded a Nobel Prize in 2015 for the drug’s success in combatting river blindness and other tropical maladies. Veterinarians also use it to prevent heartworm and treat parasitic infections in some animals.

Several ivermectin champions, boosted by the internet, have been promoting the drug as a cure or preventive for Covid-19. But promoting is not the same as knowing. Knowing requires testing in well-designed clinical trials.

Ivermectin proponents haven’t been content to wait for that research. In striking testimony before the U.S. Senate Homeland Security and Governmental Affairs Committee in December 2020, Pierre Kory, a critical care physician who formerly worked for the University of Wisconsin Health University Hospital, described the “immense potency” of ivermectin, characterizing it as effectively a “miracle drug.” “All studies are positive,” he testified, “with considerable magnitude benefits, with the vast majority reaching strong statistical significance.”

Unfortunately, and not for the first time in the Covid-19 pandemic, the hype exceeded the evidence.

The gold standard in drug development is the randomized controlled trial. These maximize the chance that the group receiving a treatment and the control group not receiving it are alike in all other respects. But even such trials must be properly conducted with adequate sample sizes, investigators and participants blinded to who is getting what, and rigorous data collection and analysis. But Kory cited several non-randomized observational studies, in which patients can receive non-standardized treatments, as well as many poor-quality controlled trials.

One of these was a trial by Ahmed Elgazzar from Benha University in Egypt. In this trial of patients with severe Covid-19, one group received ivermectin while the other, the control group, received hydroxychloroquine (people in this group should have received a placebo). According to the researchers, there was a 90% reduction in deaths in the ivermectin group, a degree of effectiveness strikingly at odds with most other studies of ivermectin and considerably better than even FDA-approved therapies for Covid-19.

A British medical student, Jack Lawrence, was assigned to evaluate the Elgazzar paper for a course and encountered a potpourri of apparent plagiarism and data fabrication. The Elgazzar paper had not been formally published in a medical journal, but had appeared instead on a preprint website called Research Square. Upon learning of Lawrence’s analysis, Research Square promptly retracted the paper.

Gideon Meyerowitz-Katz, an Australian chronic disease epidemiologist who also reviewed the Elgazzar data, found faults similar to Lawrence. Researchers often summarize large bodies of literature by statistically synthesizing trials in what are called meta-analyses. “If you remove this one study from the scientific literature,” he told The Guardian “most meta-analyses that have found positive results would have their conclusions entirely reversed.”

Where to look for higher quality data? A group called the Cochrane Collaboration spends its time conducting meta-analyses of the best-conducted clinical trials. After excluding dozens of ivermectin studies with “high risk of bias,” the collaboration left little room for optimism: “Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent Covid-19.” The group recommended that ivermectin use be restricted to clinical trials that might actually generate high quality data.

The World Health Organization and the Infectious Diseases Society of America concur. Even Merck, an ivermectin manufacturer, avers that there is “no meaningful evidence for clinical activity or efficacy in patients with Covid-19.” And just last weekend the FDA warned people not to use the drug as a treatment for Covid-19.

You are not a horse. You are not a cow. Seriously, y'all. Stop it. https://t.co/TWb75xYEY4

— U.S. FDA (@US_FDA) August 21, 2021

Yet ivermectin boosters and merchants have convinced many to use this therapy for Covid-19, particularly in Latin America where its use is so widespread that researchers have had difficulty recruiting patients for trials of other potentially effective products. In June, YouTube suspended the account of Sen. Ron Johnson (R-Wis.), a member of the Senate Homeland Security and Governmental Affairs Committee, for a week for spreading misinformation about ivermectin and hydroxychloroquine.

The increased demand for the drug, combined with enhanced scrutiny from pharmacists, has caused shortages of veterinary formulations of the drug. Inevitably, a spike in calls to Poison Control Centers connected to the use of veterinary ivermectin has followed.

The University of Oxford’s rigorously designed PRINCIPLE trial is now trying to determine if ivermectin actually benefits people with Covid-19. But until those results come in, I urge people to heed the lessons of hydroxychloroquine, bleach, and all the other purported Covid-19 cures: effective treatments will be identified through systematic scientific study, not by wishful thinking, fabrication, or miracles.

Peter G. Lurie is president of the Center for Science in the Public Interest and a former associate commissioner of the FDA.