Large Ivermectin Study Retracted

A large Egyptian study of ivermectin for COVID-19 patients has been retracted over concerns of plagiarism and serious problems with their raw data, the publisher confirmed to MedPage Today.

Michele Avissar-Whiting, PhD, editor-in-chief of the preprint server Research Square, said in an emailed statement that the study was withdrawn on July 14 "because we were presented with evidence of both plagiarism and anomalies in the dataset associated with the study, neither of which could reasonably be addressed by the author issuing a revised version of the paper."

Avissar-Whiting noted that the concerns were first raised by Jack Lawrence, a British medical student, according to The Guardian.

"Based on what Jack found, we have reason to believe the preprint's conclusions are compromised, so the withdrawal was done to stop its propagation as sound science," she said. "This is the strategy employed by a number of preprint servers, per best practice guidance."

The study was one of the largest ivermectin trials in the world, and has been included in two recent meta-analyses (Bryant et al. and Hill et al.) that received much attention for their positive results -- particularly the Hill review, which had been anticipated by a U.S. group that has long promoted ivermectin.

Some have questioned whether the positive conclusions of those meta-analyses would still stand when the Egyptian study is removed.

David Boulware, MD, MPH, of the University of Minnesota, told MedPage Today that the 400-patient Egyptian trial -- from Ahmed Elgazzar, MD, of Benha University, and colleagues -- was the largest study included in the Hill review and accounted for 20% of the total data.

Lead author Andrew Hill, PhD, of the University of Liverpool in England, said in an email to MedPage Today that his team will be "re-running our analysis with the Elgazzar trial removed."

Hill added that his team will also include a recently published 500-patient randomized controlled trial from Argentina, published in BMC Infectious Diseases, which found no effect for ivermectin in terms of preventing hospitalization in patients with COVID-19. It also found that those who received ivermectin required invasive ventilation sooner than those on placebo.

"In our published paper, we emphasized the preliminary nature of our results and the need to continue more definitive studies," Hill noted in the email.

Boulware echoed Hill's comments: "One problem with meta-analyses is that it is dependent on the underlying data," he tweeted. "Phase 3 double-blind randomized clinical trials are needed to provide definitive data." (Boulware is currently conducting a COVID-19 outpatient trial, randomizing patients to ivermectin, fluvoxamine, metformin [or a combination of two of those], or standard care within 3 days of diagnosis.)

Though the Elgazzar study is no longer available online, other publications have cited its main findings: Hospitalized patients with COVID-19 who were treated with ivermectin were 90% less likely to die than those who didn't receive the drug.

That conclusion started to fall apart when Lawrence took on a medical school assignment that had him look deeper into the paper. First, he found evidence of plagiarism, with entire paragraphs lifted from press releases and websites, according to The Guardian.

Lawrence also found that the raw data, which are available online for purchase, contradicted the study on several occasions. Gideon Meyerowitz-Katz, an epidemiologist from the University of Wollongong in Australia, also highlighted some of those discrepancies in a Medium post.

"For example, the study reports getting ethical approval and beginning on the 8th of June, 2020, but in the data file uploaded by the authors onto the website of the preprint fully 1/3 of the people who died from COVID-19 were already dead when the researchers started to recruit their patients," Meyerowitz-Katz wrote.

"Moreover, about 25% of the entire group of patients who were recruited for this supposedly prospective randomized trial appear to have been hospitalized before the study even started, which is either a mind-boggling breach of ethics or a very bad sign of potential fraud," he continued.

Elgazzar did not respond to a MedPage Today request for comment.

There are multiple ongoing phase III randomized controlled trials that will likely provide more definitive results on ivermectin, including Boulware's study and the U.K.'s PRINCIPLE outpatient trial that is aiming to enroll about 1,500 patients in its ivermectin arm.

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