The efficacy of a drug promoted by right-wing figures around the world for the treatment of Covid-19 is in serious doubt after a major study showing the treatment’s effectiveness against the virus was withdrawn due to “ethical concerns”.
A preprint study of the efficacy and safety of ivermectin, a drug used against parasites such as worms and head lice in the treatment of Covid-19, led by Dr Ahmed Elgazzar of Benha University in Egypt, was published on the Research Square website in November.
It has been claimed to be a randomized control trial, a very important type of study in medicine, as it is thought to provide the most reliable evidence about the effectiveness of interventions due to the minimal risk of confounding factors affecting outcomes. Elgazzar is listed as the chief editor of the Benha Medical Journal and is an editorial board member.
The study found that 90% of Covid-19 patients who were hospitalized and “reported significant improvement early in the period receiving ivermectin” and “significant improvement and reduction in mortality in the ivermectin-treated groups”.
But after the Elgazzar study was removed from the Research Square website on Thursday “due to ethical concerns”, the drug’s promise of a cure for the virus raises serious doubt. Research Square did not explain what those concerns were.
Jack Lawrence, a medical student in London, was one of the first to identify serious concerns about the article, leading to its retraction. Elgazzar first became aware of the preprint when he was assigned to him by a faculty member for a post that forms part of his master’s degree. He saw that the introduction to the article was almost entirely plagiarism.
It turns out that the authors ran entire paragraphs from press releases and websites about ivermectin and Covid-19 through a thesaurus to replace keywords. “Amusingly, this led them to change ‘severe acute respiratory syndrome’ at one time to ‘extremely intense respiratory syndrome,'” Lawrence said.
The data also appeared questionable to Lawrence, and the raw data several times clearly contradicted the study protocol.
“The authors claimed to only do the study on 18-80 year olds, but at least three patients in the dataset were under 18 years old,” Lawrence said.
“The authors claimed to have conducted the study between 8 June and 20 September 2020, but most of the patients who died were hospitalized and died before 8 June according to the raw data. The data were also horribly formatted and non-existent who left the hospital on 31/06/2020 includes a patient.”
There were other concerns.
“The authors claim in their article that four out of 100 patients died from mild to moderate Covid-19 in the standard treatment groups,” Lawrence said. “According to the original data, number 0 was the same as in the ivermectin treatment group. The authors claim that two patients died in the ivermectin treatment groups for severe Covid-19, but the number four in their raw data.”
Lawrence and the Guardian sent Elgazzar an extensive list of questions about the data, but received no response. The university’s press office also did not respond.
Lawrence, an Australian chronic disease epidemiologist Gideon Meyerowitz-Katz of the University of Wollongong and a data analyst at Linnaeus University in Sweden, who reviews scientific papers for errors to help with more comprehensive analysis of data and study results. Contacted Nick Brown.
Brown has created a comprehensive document that she submitted to the Guardian, exposing the many data errors, inconsistencies and concerns. According to their findings, the authors had clearly duplicated data among patients.
“The main mistake is that at least 79 of the patient records are obvious clones of other records,” Brown told the Guardian. “It’s definitely the hardest to explain as an innocent mistake, especially since the clones aren’t even pure duplicates. There are signs that they’re trying to change one or two areas to make them look more natural.”
Other studies on ivermectin are still in progress. In the UK, the University of Oxford is testing whether giving people with Covid-19 ivermectin prevents them from going to the hospital.
The Elgazzar study was one of the largest and most promising studies to show that the drug could help patients with Covid, and is often cited as evidence of its effectiveness by the drug’s proponents. That’s despite a peer-reviewed article published in the journal Clinical Infectious Diseases in June showing that ivermectin “is not a viable option for treating COVID-19 patients.”
Meyerowitz-Katz told the Guardian that “this is one of the biggest ivermectin studies out there,” and it appeared to him that the data was “totally fake.” This was related to the fact that two meta-analyses of ivermectin for the treatment of Covid-19 included the Elgazzar study in the results. A meta-analysis is a statistical analysis that combines the results of multiple scientific studies to determine what the general scientific literature has found about a treatment or intervention.
“Because the Elgazzar study is so large and so overwhelmingly positive – showing a 90% reduction in mortality – it drastically skews the evidence in favor of ivermectin,” Meyerowitz-Katz said.
“If you remove this one study from the scientific literature, all of a sudden there are very few positive randomized control trials of ivermectin for Covid-19. Indeed, most meta-analyses that find positive results completely reverse their results if you just get rid of this research.”
Kyle Sheldrick, a Sydney physician and researcher, also independently expressed concern about the paper. He found that the numbers the authors provided for the few standard deviations (a measure of variation in a set of data points) mentioned in the tables in the paper were “mathematically impossible” given the range of numbers given in the same table.
The completeness of the data is further evidence suggestive of possible fabrication, Sheldrick said, noting that this is nearly impossible in real-world conditions. It also identified patient deaths and duplication of data.
Ivermectin has gained momentum in Latin America and India, based largely on evidence from preprint studies. In March, the World Health Organization warned against the use of ivermectin outside of well-designed clinical trials.
Conservative Australian lawmaker Craig Kelly, who also promoted the use of the antimalarial drug hydroxychloroquine to treat Covid-19, was among those promoting ivermectin – although there is no evidence that it works. Several Indian media outlets published news about Kelly last week. Asked Uttar Pradesh loan the state’s prime minister, Adityanath, to Australia to release ivermectin.
Lawrence said what began as a simple university assignment led to a thorough investigation into a seemingly scientific fraud “while there was sheer ivermectin hype… dominated by a mix of right-wing figures, anti-vaccine folks and outright conspirators.” .
“While science is tending to correct itself, something is clearly broken in a system like the Elgazzar newspaper that could allow a problem-filled study to run unopposed for seven months,” he said.
“Thousands of highly educated scientists, doctors, pharmacists, and at least four major drug regulators overlooked a fraud as blatant as it may have come with a flashing neon sign. All the more gruesome to happen in the midst of an ongoing global health crisis of epic proportions. ”