- There has been a lot of discussion on ivermectin as a possible prophylaxis and treatment for Covid-19.
- In November, a study studying the value of the drug for Covid showed promising findings, and was highly cited in other papers.
- But independent researchers conducted in-depth investigations and found that the original study was potentially based on fraud, inconsistencies, and plagiarism.
An extensive preprint study showing that the anti-parasitic drug, ivermectin, played a significant role in reducing the risk of Covid-19 infection, hospitalisation, and death has been withdrawn due to "ethical concerns".
The research was led by Dr Ahmed Elgazzar from Benha University in Egypt and was published on Research Square in November 2020. It was presented as the results of a multi-centre, 600-patient study evaluating the use of the drug in preventing and treating Covid-19.
Elgazzar and colleagues from two Egyptian universities wrote that ivermectin significantly reduced the length of Covid-19 patients' hospital stay, as well as the number of Covid-related deaths, compared to standard Egyptian treatment protocols. Additionally, the researchers claimed that the drug played a substantial prophylactic role in Covid-19. In other words, it prevented the onset of the disease, they said.
It was also one of the largest studies that had highly encouraging findings, on ivermectin for Covid-19 to date. As a result, it has been cited in other high-profile research also looking at its effectiveness against Covid and became a critical component of the pro-ivermectin case.
On Thursday, 15 July, however, Research Square said it, "... has withdrawn this preprint", but did not cite the reasons for the retraction.
The authors' "ethically dubious behaviour" was first observed by Jack Lawrence, a medical student based in London. In an article published by Grftr News, he wrote that the introduction of the study was almost entirely plagiarised from various sources, including press releases and other studies – only, the authors disguised this by changing some of the words.
"Humorously, this led to them changing 'severe acute respiratory syndrome' to 'extreme intense respiratory syndrome' on one occasion," Lawrence told The Guardian.
Moreover, there had also been some protocol issues: "The authors claimed to have done the study only on 18-80- year-olds, but at least three patients in the dataset were under 18," Lawrence wrote.
According to his investigation, while the authors claimed they conducted the study between 8 June – 20 September 2020, the raw data indicates that most of the patients who died were admitted to hospital and died before 8 June. He added: "The data was also terribly formatted, and includes one patient who left hospital on the non-existent date of 31/06/2020."
There were additional concerns observed by Lawrence: "In their paper, the authors claim that four out of 100 patients died in their standard treatment group for mild and moderate Covid-19.
"According to the original data, the number was 0, the same as the ivermectin treatment group. In their ivermectin treatment group for severe Covid-19, the authors claim two patients died, but the number in their raw data is four."
After detecting further concerns, Grftr News sent through a copy of the data to Nick Brown, a data analyst affiliated with Linnaeus University in Sweden who reviews scientific papers for errors. Brown analysed the research and posted his concerns to his blog. He found several problems, "... from numbers containing non-numeric characters, confusion about date formats, and—most damningly of all—multiple incidences of data being copied between patients," said Lawrence.
Brown told The Guardian: "The main error is that at least 79 of the patient records are obvious clones of other records. It's certainly the hardest to explain away as innocent error, especially since the clones aren't even pure copies. There are signs that they have tried to change one or two fields to make them look more natural."
When Lawrence alerted Research Square about his and Brown's findings, they quickly removed the paper citing "ethical concerns".
Grftr News approached the Benha University Research Ethics Committee and the paper's authors with several questions, but did not receive any response. Similarly, The Guardian reports that Elgazzar did not respond to a comprehensive list of questions that they sent.
"The study had formed a crucial piece of evidence in the pro-ivermectin case and its removal largely destroys the current scientific case for using the drug in Covid-19 care," said Lawrence.
Since this study was so large and showed very promising results, it skewed the evidence in favour of ivermectin, Gideon Meyerowitz-Katz, an Australian chronic disease epidemiologist from the University of Wollongong, told The Guardian.
"If you remove this one study from the scientific literature, suddenly there are very few positive randomised control trials of ivermectin for Covid-19," he said. "Indeed, if you get rid of just this research, most meta-analyses that have found positive results would have their conclusions entirely reversed."
Lawrence concluded that, "... something is clearly broken in a system that can allow a study as full of problems as the Elgazzar paper to run unchallenged for seven months. Thousands of highly educated scientists, doctors, pharmacists, and at least four major medicines regulators missed a fraud so apparent that it might as well have come with a flashing neon sign."
Cited in other research
"Despite never passing peer-review or being published in any scientific journal, the Elgazzar study went on to get cited in approximately 30 other studies, including several peer-reviewed ones in prominent journals," said Lawrence.
It also drew scepticism from the South African National Department of Health, who, in January 2021 pointed to a lack of specific details in the study and concluded that the paper had a, "... high risk of bias due to reporting issues".
The DoH also updated its ivermectin review on 18 June. According to the experts who reviewed existing studies, current evidence on the drug for Covid is insufficient to recommend its use for the treatment of Covid.
Much of the randomised clinical trial evidence, they said, "... consists of trials of low methodological quality, for the most part with small sample sizes and disparate interventions and controls, limiting the confidence in any conclusions with respect to ivermectin".
Another study published in BMC Infectious Diseases on 2 July found that ivermectin was not beneficial in reducing Covid-related hospitalisation, GroundUp reported.
Currently, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) advise against the use of ivermectin for Covid-19. The World Health Organization (WHO) only recommends its use within the context of clinical trials.