Update (February 11): The American Journal of Therapeutics has issued expressions of concern on two published papers summarizing ivermectin’s use in COVID-19 patients. One of those papers was a reworked version of the manuscript by Pierre Kory and colleagues that had previously been rejected by Frontiers after editors determined that it contained “a series of strong, unsupported claims.” The other paper was authored by a separate research group. Both expressions of concern cite “allegations of inaccurate data collection and/or reporting” in at least one of the studies included in the reviews. The journal’s editor-in-chief, Peter Manu, tells Retraction Watch that any further action will hinge on the results of independent investigations at other institutions into those allegations.

A special issue of Frontiers in Pharmacology on repurposing existing drugs as COVID-19 treatments has been axed following a dispute between the journal’s publisher and the issue’s guest editors over which submissions should be accepted.

The dissolution of the issue, which was entitled “Treating COVID-19 with Currently Available Drugs,” is the latest move in a row that’s continued for weeks. At the beginning of March, Frontiers issued a rejection for a manuscript on the antiparasitic drug ivermectin that had been provisionally accepted, after the publisher identified “a series of strong, unsupported claims” in the paper and determined that it did “not offer an objective nor balanced scientific contribution,” Frontiers’s chief executive editor Frederick Fenter said in a statement at the time. 

See “Frontiers Removes Controversial Paper on Ivermectin

Now, following disagreements about other submissions and more than a month of failed negotiations between Frontiers and the guest editors about how to proceed, the editors have followed through on previous threats to resign, while the publisher confirms it has pulled the issue page from its website.

According to Fenter, situations such as this do crop up from time to time. “When you deal with literally tens of thousands of people every year, you’re going to wind up having misunderstandings,” he tells The Scientist. “You do have disagreements with editors in many different contexts . . .  particularly around rejections.” The same goes for peer review, he adds. It’s “a human process and occasionally things will go wrong.”

In contrast, the editors who resigned consider Frontiers’s actions “extraordinary and unprecedented,” they write in a six-page resignation statement shared with The Scientist. The signatories are four of the five guest editors of the special issue: physician-scientist and consultant Robert Malone; Piero Sestili and Maria Cristina Albertini of the University of Urbino Carlo Bo in Italy; and Howard Haimes, formerly of US defense and analytics company SAIC. The fifth editor, France-based physician Stéphane Arminjon, was not a signatory on the resignation statement and did not respond to requests for comment.

The editors emphasize that the papers at the center of the disagreement had passed peer review. “The scientific process requires fair, open, and transparent peer review to proceed effectively and efficiently—particularly at this time and for this topic,” the editors write in their statement, which was sent to Frontiers staff and to authors of papers in the special issue yesterday (April 27). “The actions of ‘Frontiers’ in this matter clearly violate well established norms and processes for peer review and publication of scientific works and intellectual contributions.”

Fenter says that the handful of already published papers will remain online on the Frontiers in Pharmacology website, but will no longer be part of a particular issue, and other submissions will be handled by a new group of editors appointed by the publisher.

A platform for papers on early-stage COVID-19 research

The idea for the special issue came from Malone and Albertini, who met last year through virtual meetings with various other researchers about COVID-19 data, Malone tells The Scientist. They felt frustrated by the difficulty of disseminating preliminary, observational data of the kind needed to justify larger clinical trials on currently available drugs, Malone says, and wanted to “help create an opportunity for these earlier-stage studies to be published.” 

With Albertini’s colleague Sestili, they proposed the idea of a special issue to Frontiers late last year and developed a summary of the issue’s scope. The plan was to gather multiple types of articles—including case series reports and preliminary observations as well as broader reviews and meta-analyses—on various unproven COVID-19 treatments. 

It’s their business . . . academic publication of peer reviewed research. And now they’re like, ‘We can’t do that because it’s too risky.’ They can’t have it both ways.

—Robert Malone, guest editor on the special issue of 
Frontiers in Pharmacology

Frontiers accepted the proposal, Malone says; Haimes and Arminjon joined as editors shortly afterward, and the team began soliciting manuscripts and contributing their own articles for the issue. 

Malone coauthored and submitted a couple of manuscripts on famotidine, a stomach acid drug sold under the brand name Pepcid. As former chief medical officer of Alchem Laboratories Corporation, Malone has previously been involved in work on famotidine: in April 2020, Alchem and its subcontractor Northwell Health were awarded a $20.7-million government contract to test the drug in combination with hydroxychloroquine in patients with moderate to severe COVID-19, the Associated Press reported last summer. 

Malone left that study and resigned from Alchem shortly after the contract was awarded, citing a difficult working environment, he told the AP and confirms in an email to The Scientist.

See “Stomach & Heartburn Drugs Linked with COVID-19 Outcomes

Because Malone was one of the guest editors of the Frontiers in Pharmacology special issue, papers that he had coauthored were managed by an independent editor appointed by Frontiers. 

In his capacity as editor, Malone invited Pierre Kory—the president of an advocacy organization called the Front Line COVID-19 Critical Care (FLCCC) Alliance that has pushed for the use of ivermectin in COVID-19 patients despite widespread agreement among public health and medical communities that the evidence doesn’t support its use—to submit a paper on the drug. 

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

For that paper, Malone handled the reviewer selection and other aspects of the paper acceptance process. Haimes and three others reviewed the manuscript, and it was provisionally accepted in January 2021. The paper’s abstract was posted on the journal’s website, and proceeded to rack up tens of thousands of views over the following few weeks. 

Frontiers steps in after concerns are raised

Multiple readers contacted Frontiers shortly after the ivermectin paper’s abstract was posted online, with concerns about some of its assertions, Fenter writes in emailed responses to questions by The Scientist. “For integrity purposes, we investigate any concerns raised about a paper, regardless of publication stage or journal,” he adds. 

Frontiers’s investigation concluded that the paper lacked objectivity, contained unsubstantiated claims, and inappropriately included the FLCCC Alliance’s own COVID-19 treatment protocol, according to Fenter’s statement last month. He adds over email that “the types of concerns identified in this case would very likely have led to a retraction in due course.”

The ivermectin paper was officially rejected on March 1. Frontiers removed the paper’s abstract from the website, and Fenter and colleagues began an audit of other papers in the issue. By then, one of Malone’s papers, a discussion of the possible mechanisms of famotidine against COVID-19, had been accepted. (It was published on March 23.)

On March 11, another paper coauthored by Malone—which reported a case series of 25 patients treated at a community hospital with a combination of famotidine and the anti-inflammatory drug celecoxib and had not been provisionally accepted—was rejected at the post-review stage. The primary reason was that uncontrolled case studies of patients can’t provide new or meaningful insights into a drug’s effects in COVID-19, particularly since those patients were also receiving other drugs such as vitamin C in addition to famotidine and celecoxib, according to an email explaining the decision sent to the authors by one of Frontiers in Pharmacology’s chief editors.

We’re never going to accelerate an acceptance of a paper or accept anything that hasn’t been validated because the editors tell us that if it’s not published by Friday, they’re going to go to the press.

—Frederick Fenter, Frontiers

Malone and the other guest editors of the special issue objected to what they viewed as publisher interference on the ivermectin and famotidine-celecoxib papers, Malone tells The Scientist. Both papers had received predominantly favorable peer reviews, the editors’ statement emphasizes, and the famotidine-celecoxib paper was “clearly and explicitly described as a case series, and this clinical evaluation (case series) is explicitly allowed for publication both as a general category for this journal and in this special topic volume.”

In multiple rounds of emails and Zoom conversations in March and April, the two parties discussed how to proceed with these papers and with the issue in general, but by all accounts failed to find a mutually satisfactory solution. In mid-April, the guest editors told the publisher they were ready to resign and provided the journal with an ultimatum for finding a solution—a move that the editors say in their statement was necessary to receive a timely response.

Fenter points out that part of the editors’ ultimatum involved a threat to tell the media about what had happened if their demands weren’t met. “We do not operate that way,” he says in an interview with The Scientist. “We’re never going to accelerate an acceptance of a paper or accept anything that hasn’t been validated because the editors tell us that if it’s not published by Friday, they’re going to go to the press.”

In the end, the publisher dissolved the issue and notified authors on papers in the issue in an email on April 19. The Scientist reached out to several authors of papers already published as part of the issue but did not receive responses by deadline.

Frontiers also removed the issue’s webpage entirely—a procedure that Fenter says is standard policy at Frontiers in this kind of situation.

The role of peer reviewed science

Neither famotidine nor ivermectin are recommended by US health organizations for the treatment or prevention of COVID-19, although clinical trials are underway for both drugs. Ivermectin has been a particular subject of misinformation during the pandemic, prompting repeated warnings and guidance from health organizations and one of the drug’s manufacturers, Merck, that there is insufficient evidence at this time to recommend its use as a COVID-19 treatment. 

Malone argues that early-stage results need to be published in order to inform larger trials, and blames previous publishing scandals during the pandemic—in particular, last summer’s high-profile retraction of a discredited study of hydroxychloroquine—for making publishers and journal editors nervous about providing a platform for preliminary research or for conclusions that could turn out to be wrong. 

See “The Surgisphere Scandal: What Went Wrong?

Publishers have an obligation to assume these risks, he argues, adding that Frontiers shouldn’t have accepted the proposal for a special issue that explicitly allowed for weak or early-stage evidence if they weren’t willing to see it through. “This is the business they’re in,” he says. “It’s their business . . . academic publication of peer reviewed research. And now they’re like, ‘We can’t do that because it’s too risky.’ They can’t have it both ways.” 

In the last few weeks, Kory and his coauthors have found another journal to accept their ivermectin manuscript: The American Journal of Therapeutics confirms in an email to The Scientist that a version of the paper will be published in the journal’s May issue next week, and the FLCCC Alliance has already spread the news on social media. Malone tells The Scientist that he and his colleagues are preparing their rejected manuscript for another journal too.

Fenter says that the process has been frustrating, but that all decisions taken about papers in the issue were made as they should have been: on the basis of each paper’s quality and contribution to the literature. 

“We have the peace of mind of knowing that we’re doing the right thing—that’s all we care about,” he says. “We make the decision based on what has to be done for the sake of the integrity of the scientific literature, and the sake of our policies, and the sake of making sure at Frontiers that we’re working very, very hard only to validate and publish the articles that deserve to enter into the scientific literature.”

Clarification (April 29): The second and third paragraphs of this article have been updated to clarify the guest editors’ actions. 

Correction (April 29): A previous version of this article implied that Howard Haimes is currently affiliated with SAIC. An SAIC company spokesperson tells The Scientist that he left the company earlier this month. The Scientist regrets the error.