Scientists have cast doubts over an ivermectin study that said it had found a "favorable outcome" when giving the medicine to COVID patients—though its authors have defended it.
The May 2021 study was a randomized, double-blinded trial in Israel that compared non-hospitalized patients receiving ivermectin for three days to those who were given a placebo. There were 47 patients in the ivermectin group, and 42 in the placebo group.
The study, which is a pre-print available to read on the medRxiv pre-print repository, concluded that it had identified "significantly lower viral loads and viable cultures" in a group of people treated with ivermectin compared to a placebo group. It has since been cited by several news outlets.
But Gideon Meyerowitz-Katz, a chronic disease researcher and science journalist, criticized the study in a series of Twitter posts on Tuesday.
This study is a common citation of ivermectin believers, has been reported widely, and I think is a great teaching tool in how little effort it takes to be critical about research findings 1/n pic.twitter.com/YDZNB1JP5R
— Health Nerd (@GidMK) September 7, 2021
He said that there is a discrepancy between the final study and what the study authors said they would do in pre-registration. The study's pre-registration can be found here.
Meyerowitz-Katz said the discrepancy involves people who were excluded from the study based on what is known as the patients' CT value—simply, a measure of how much virus someone has in their system.
The study states that COVID patients with a CT value of over 35 in the first two tests were excluded, despite this not being included in the study's initial exclusion criteria. "It appears that the authors have added an extra exclusion criteria that is applied after randomization and treatment," Meyerowitz-Kats tweeted. "If you add these people back in, the results of the study entirely lose their significance," he added.
7/n It appears that the authors have added an extra exclusion criteria that is applied AFTER randomization and treatment. This is "tested Ct>35" in the first two tests pic.twitter.com/V5ZfCZWhv7
— Health Nerd (@GidMK) September 7, 2021
Dr. David Boulware is professor of medicine in the Division of Infectious Diseases and International Medicine at the University of Minnesota with formal training in clinical trials. He told Newsweek the criticisms of the study were "spot on" and that the changes "seem very much like cherry-picking."
"While post-hoc changes can be made, they need to be explained in great detail," he said. "And preferably before looking at the group level data."
Dr. Stephen Griffin is chair of the virus division, microbiology society and academic lead for laboratories at the Leeds Institute of Medical Research. He said Meyerowitz-Katz' criticism "makes perfect sense," and added: "You can't add extra exclusion criteria after randomizing.
"The trial is ongoing and I will be interested to see the outcome, but until then I would echo the advice from WHO and urge that Ivermectin is not used off-label to treat COVID. The rise in U.S. poison centers dealing with Ivermectin-related issues is deeply troubling."
Dr. Simon Maxwell of the Clinical Pharmacology Unit at the University of Edinburgh said the study is "interesting but flawed" due to the change in protocol, and pointed to several large-scale ivermectin trials currently underway. "Let's all await the clinical trials before advocating mass deployment," he told Newsweek.
In response to the criticisms, two of the study's authors, doctors Asaf Biber and Eli Schwartz at The Center for Geographic Medicine and Tropical Diseases at the Chaim Sheba Medical Center in Israel, told Newsweek the criticisms had "missed the point."
They said in a joint statement: "As our target population was non-hospitalized patients who were sent to dedicated hotels for isolation due to their proven cases, we were not expecting to encounter patients who were already negative for COVID-19 upon recruitment, which was done up to 48 hours after admission to the hotel.
"We became aware of this phenomenon during the study—we presume it occurred either from a mistaken diagnosis at the community level or due to a fast recovery before entering the hotels.
"Subsequently when we became aware of the situation, these patients were excluded from the study, still while being blinded to the group, and we added more patients.
"Our results regarding the viral load and pace in which patients became non-infectious are encouraging, demonstrating the favorable impact of ivermectin."
Ivermectin is an anti-parasitic medication that has been put forward as a potential COVID treatment due to a number of studies suggesting it may be beneficial to patients.
At the same time, the U.S. Food and Drug Administration (FDA) has warned people not to use it to treat or prevent COVID, citing a lack of data, misuse, and the effects of overdose.
This article has been updated to include a response by the study's authors.
