Frontiers Removes Controversial Ivermectin Paper Pre-Publication
Frontiers Removes Controversial Ivermectin Paper Pre-Publication

Frontiers Removes Controversial Ivermectin Paper Pre-Publication

A review article containing contested claims about the tropical medicine drug as a COVID-19 treatment was listed as “provisionally accepted” on the journal’s website before being removed this week.

Catherine Offord
Catherine Offord
Mar 2, 2021

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The editors of Frontiers in Pharmacology have taken down an article about the use of the antiparasitic drug ivermectin in COVID-19 patients. The paper, which was written by members of an organization called the Front Line COVID-19 Critical Care Alliance (FLCCC), had been provisionally accepted and posted in abstract form by the journal in January, but was ultimately rejected this Monday (March 1). The editors determined that it contained unsubstantiated claims and violated the journal’s editorial policies.

By the end of last week, the abstract had been viewed more than 85,000 times, according to snapshots available on the internet archive.

The paper’s removal has drawn anger from members of the FLCCC and its followers. In comments on Twitter and in an interview with The Scientist, the organization’s president, Pierre Kory, describes the move as “censorship.” He adds in the interview that the paper had already successfully passed through multiple rounds of review. In reversing the paper’s acceptance, the journal is “allowing some sort of external peer reviewer to comment on our paper,” he says. “I find that very abnormal.”

Ivermectin is widely used in tropical medicine to treat parasitic infections, but its use as a COVID-19 drug has been controversial since the beginning of the pandemic, with major health organizations consistently stating that there is insufficient evidence for its efficacy in prevention or treatment of the disease.

See “Surgisphere Sows Confusion About Another Unproven COVID-19 Drug

The FLCCC’s paper (also posted on the organization’s website) reviewed epidemiological and clinical evidence on ivermectin’s use in people infected with and exposed to SARS-CoV-2. In it, the authors argued that health agencies such as the National Institutes of Health (NIH) should update their recommendations to include the drug.

Frontiers takes no position on the efficacy of ivermectin as a treatment of patients with COVID-19, however, we do take a very firm stance against unbalanced or unsupported scientific conclusions.

—Frederick Fenter, Frontiers

After being contacted by The Scientist, the journal posted a statement from Frontiers’s chief executive editor, Frederick Fenter, saying that “Frontiers takes no position on the efficacy of ivermectin as a treatment of patients with COVID-19, however, we do take a very firm stance against unbalanced or unsupported scientific conclusions.”

During review of the article in what the journal refers to as “the provisional acceptance phase,” Fenter says in the statement, members of Frontiers’s research integrity team identified “a series of strong, unsupported claims based on studies with insufficient statistical significance, and at times, without the use of control groups.”

The statement continues: “Further, the authors promoted their own specific ivermectin-based treatment which is inappropriate for a review article and against our editorial policies. In our view, this paper does not offer an objective nor balanced scientific contribution to the evaluation of ivermectin as a potential treatment for COVID-19.”

The statement provided no information about why these concerns had been raised and acted on now, rather than earlier in the publication process.

This isn’t the first time that Kory and his colleagues at FLCCC have been accused of making unsubstantiated claims about ivermectin. In December, Kory gave a statement at a US Senate hearing on COVID-19 treatments in which he called ivermectin “effectively a ‘miracle drug’” that could obliterate disease transmission and prevent illness—claims that Associated Press fact-checkers labelled “False” at the time. Kory, who formerly oversaw critical care at the UW Health in Wisconsin, tells The Scientist that he now regrets using “miracle” and other hyperbolic terminology.

Later in December, FLCCC founder Paul Marik, the first author on the now-rejected Frontiers manuscript and a professor at Eastern Virginia Medical School, wrote a paper reviewing ivermectin that included references to debunked papers, including an observational study of ivermectin in COVID-19 patients led by now-discredited Surgisphere Corporation. That study, which had been posted on the preprint server SSRN, was taken down at the request of one of the authors back in May after concerns were raised about the provenance of the company’s data.

There have been a number of trials of ivermectin in COVID-19 patients, although they haven’t met all the criteria that scientists typically deem necessary to generate strong evidence—that is, being randomized, well-controlled trials with hundreds or thousands of patients and findings published in a peer-reviewed journal.

The NIH, which last updated its advice on ivermectin in COVID-19 patients on February 11, 2021, states that most of the studies claiming to show benefits of ivermectin contain “incomplete information and significant methodological limitations, which make it difficult to exclude common causes of bias.”

The agency concludes that “there are insufficient data . . . to recommend either for or against the use of ivermectin for the treatment of COVID-19,” and calls for “adequately powered, well-designed, and well-conducted clinical trials.”

Kory argues that these common criticisms ignore the fact that there are several groups of researchers in favor of ivermectin’s use, and that the urgency of the situation means that health organizations should be looking at smaller, uncontrolled trials and observational data as well as gold-standard trials. He adds that larger trials of the drug are underway or planned. The multicenter TOGETHER trial led by researchers at McMaster University, for example, was announced earlier this year.

Responding to the Frontiers statement’s invitation to the authors to submit a revised version of the paper, Kory says that while he would have been open to removing mentions of his own team’s treatment protocol, he doesn’t want to work with the journal again. “There was no communication with us, no telling us of their concerns, no discussion” during this process, he says. “The idea that I would resubmit to that journal is fairly preposterous, don’t you think?”