The available scientific evidence does not support the use of ivermectin, an antiparastic drug, for the treatment or prevention of COVID-19 outside the context of clinical trials, according to a new report from Cochrane, an international organization that reviews medical research and provides guidance about clinical practice.

Ivermectin has been the subject of much misinformation during the pandemic, prompting multiple health organizations and one of the drug’s manufacturers to issue warnings throughout the past year that there is not sufficient evidence to recommend its use for COVID-19 beyond a trial setting. In the new report, researchers in Germany and the UK sifted through the literature on ivermectin and came to broadly the same conclusion.

“Based on the current very low- to low-certainty evidence, we are uncertain about the efficacy and safety of ivermectin used to treat or prevent COVID-19,” the authors write in their report, posted last week (July 28). “The completed studies are small and few are considered high quality. . . . Overall, the reliable evidence available does not support the use ivermectin for treatment or prevention of COVID-19 outside of well-designed randomized trials.”

“The hype around ivermectin is driven by some studies where the effect size for ivermectin is frankly not credible,” Paul Garner, the coordinating editor of the Cochrane Infectious Diseases Group, says in a statement. “Careful appraisal is the cornerstone of Cochrane’s work, and with such extreme public demands for a drug to work during the pandemic, it remains vital that we hold onto our scientific principles to guide care.”

The Cochrane review notes an “urgent need” for good quality randomized controlled trials of the drug.

The team’s final analysis included 14 randomized controlled trials with a total of 1,678 adults. Six of the studies were double-blinded and placebo-controlled—factors considered to improve the quality of evidence in drug trials. Nine of the 14 studies focused on moderate COVID-19 cases in hospital settings, four on mild cases in outpatients, and one on the use of ivermectin as a preventive medicine. 

The team identified an additional 38 studies that failed to meet the review’s inclusion criteria, mainly because they contained problematic comparisons or data, or otherwise didn’t meet scientific standards for strong evidence. For example, nearly a third of the studies evaluated ivermectin alongside other treatments that varied between different groups of patients, making it difficult to extract the effect of ivermectin, specifically, from the data. Several studies classified people as COVID-19 patients without testing to make sure they had the disease with a PCR or antigen test.

One of the excluded studies, a widely cited paper first posted late last year on the preprint server Research Square, was withdrawn a couple weeks ago following allegations of data manipulation. The study, led by researchers in Egypt, claimed to have found a dramatic effect of ivermectin treatment on COVID-19 outcomes. However, researchers identified multiple inconsistencies in the data, The Guardian reported in July, particularly regarding the numbers of patients and their dates of hospital admission. 

One patient was even reported to have left the hospital on the “non-existent date of 31/06/2020,” Jack Lawrence, a medical student in London who identified problems in the paper, tells The Guardian. 

Another study that was not included in the Cochrane review, this one carried out in Argentina, has come under increased scrutiny from scientists in the last few days after epidemiologist and blogger Gideon Meyerowitz-Katz documented multiple inconsistencies—including numbers of patients that don’t add up and implausible effect sizes—on Twitter. “As far as interventional observational trials go, this is probably the worst one I’ve ever seen,” he writes.

The Cochrane review notes an “urgent need” for good quality randomized controlled trials of the drug, and identifies more than 30 ongoing studies. They include the PRINCIPLE trial run by the University of Oxford and the National Institutes of Health ACTIV-6 study.

“The findings from these studies may help to answer more clearly the question of ivermectin and its effects in treating and preventing COVID-19 in the future,” the authors write.