Brazil study of ivermectin as COVID-19 prevention flawed, experts say

Ivermectin is not FDA approved for use against COVID-19 and there is no scientific consensus yet on its effectiveness in treating or preventing the virus. But a new study from Brazil has supporters of the drug re-proclaiming the drug’s effectiveness on social media and beyond.

“Large peer-reviewed study proves ivermectin works,” reads the headline. an article from January 25 widely shared on Facebook.

The article was reported as part of Facebook’s efforts to combat fake news and misinformation on its News Feed. (Learn more about our partnership with facebook.)

We wanted to learn more about whether the study could indeed change the course of the ongoing debate about the use of ivermectin for COVID-19. But experts in the field criticized the study as having critical flaws involving incomplete methodology and data that undermine what, if any, it adds to research.

The article was written by a group called Frontline COVID-19 Critical Care Alliance, also called FLCCC, which describes itself as a nonprofit organization of critical care specialists dedicated to developing prevention and treatment protocols for COVID-19. According to the group’s website, defenders for the use of ivermectin in the treatment of COVID-19.

One of the study’s co-authors told PolitiFact he couldn’t say the research had “proved” ivermectin to be effective. And he said nothing replaces vaccines. On the contrary, the manuscript advocates ivermectin as an additional tool.

Neither the FDA nor the WHO recognizes ivermectin for COVID-19

Ivermectin tablets and topical forms of the drug are FDA-approved for use in humans to treat parasites and certain skin conditions, but not COVID-19. There are also animal-only formulations of the drug used to treat and prevent heartworms and other parasites.

Asked specifically about Facebook’s claim, an FDA spokesperson said the agency doesn’t typically comment on third-party research, but assesses it as part of a body of evidence when forming its advice.

And nothing in his position has changed.

“Currently, the FDA has not cleared or approved the use of ivermectin to prevent or treat COVID-19 in humans,” Chanapa Tantibanchachai, an FDA spokesperson, wrote in an email. at PolitiFact. “To date, published clinical trials have shown mixed results.”

Tantibanchachai said that while ivermectin can be prescribed by doctors for COVID-19 if they deem it appropriate, “safety and effectiveness” have not been established for this use and cautioned that the medicine could negatively interact with other medicines.

The World Health Organization also still recommends against using ivermectin to treat COVID-19 outside of clinical trials. A WHO spokesperson said the organization is tracking research on ivermectin.

“To date, there are no plans to review our guidelines on ivermectin immediately, but that could change,” the spokesperson said.

The Brazil study

The FLCCC story shared on Facebook links to a study published on January 15 in the scientific journal Cureus. Its authors, two of whom are members of the FLCCC, concluded that “regular use of ivermectin as a prophylactic agent was associated with a significant reduction in the rates of infection, hospitalization and mortality from COVID-19”, on the basis of an observational study of 159,561 18-year-old residents. and more in Itajaí, Brazil.

According to the study, between July 7, 2020 and December 2, 2020, 113,845 participants in a citywide program took the drug, while 45,716 did not. Those who took ivermectin caught COVID-19 at a rate of 3.7%, while those who did not had an infection rate of 6.6%.

After adjusting for variables, the authors reported finding a 67% reduction in the hospitalization rate and a 70% reduction in the death rate among ivermectin users.

That sounds promising, but two experts not associated with the study pointed to serious research shortcomings, including leaving questions about whether those identified as taking ivermectin actually took it as prescribed. They also raised questions about the conflicts of interest of some of its authors.

Methodological concerns

Johns Hopkins Novel Coronavirus Research Compendium epidemiologist Dr Nikolas Wada raised concerns about the study’s uncertainty about who was “really taking ivermectin and vice versa” and the poor control of factors that can predispose someone to catching COVID-19, among other outcomes.

“My main conclusion,” Wada said, “is that this article adds almost nothing to the knowledge base regarding ivermectin and COVID-19, and certainly does not prove its effectiveness as a prophylaxis.”

Gideon Meyerowitz-Katz, an epidemiologist and doctoral student at the University of Wollongong in Australia who writes often about COVID-19, said the research lacked key information about study participants, including how many Itajaí residents were already taking ivermectin before the program began and how many continued taking it full doses of the drug as prescribed.

“This type of epidemiological study is very prone to bias resulting from inherently different characteristics between intervention and control groups,” Meyerowitz-Katz said. “There’s essentially no information on how many people in the intervention or control group actually took ivermectin, which is a pretty important consideration if that’s what the authors were trying to figure out. investigate.”

Meyerowitz-Katz detailed some of his concerns about the study in a long twitter thread in December, when the study was in preprint, a preliminary version that has not been peer-reviewed.

He said little had changed in the published version.

Itajaí’s municipal health department said in January 2021 – a year before the study was published – that 138,216 residents had taken the first dose of ivermectin when it began distributing the drug as part of a city-wide program. That number fell to 93,970 people taking the second and third doses and 8,312 taking the fourth and fifth doses, the department said.

What the study authors say

The study authors acknowledged the uncertainty regarding the drug regimen in the “discussion” section of the publication. Dr. Flavio Cadegiani, corresponding author of the study, also addressed it in an email to PolitiFact, saying the results would be even better in a controlled study if all users took the drug regularly.

But Cadegiani defended the study’s methodology.

“The limitations of the study are those inherent in any population-based observational study,” said Cadegiani, who said he used a method called propensity score match “to increase the level of certainty of the results.”

Cadegiani said that in addition to showing positive results for ivermectin, the study explicitly states that “nothing replaces vaccines.”

Dr. Lucy Kerr, the study’s lead author, responded to criticism in the comments section below the study, writing that the data was comprehensive and that “the most relevant clinical variables that affected COVID-19 mortality -19 have been taken into account”. She said the study was “strong, robust, accurate” and “very high quality”.

We contacted Kerr by email, but got no response.

As to whether the title of the article’s claim that the study “proves” that ivermectin works, even Cadegiani isn’t so sure, despite being a member of the FLCCC, the group that promote the study.

“Our job was to test whether in this population ivermectin would be effective or not, in terms of protecting against COVID-19 infection, hospitalizations or death. At least from what we received, it seemed work. And I didn’t believe it. at all,” he told PolitiFact.

“Now the concept of being ‘proven’ is scientifically hard to say – even a precise definition is missing,” he said. “I never said it was proven anywhere. How people interpret and claim, that’s not in my control.”

Conflicts of interest

Wada and Meyerowitz-Katz, who were not involved in the study, each pointed to potential conflicts of interest with the study authors. They noted that although the preprinted version of the study mentions that two of its authors received money from a pharmaceutical company that manufactures ivermectin, the published version omits this detail.

The pre-print study said that Kerr had received funding from Vitamedic “unrelated to this study” and that Cadegiani had been paid for consulting services by the company, also unrelated to the study, and that he had given his all for patient care and research on COVID-19. In an email to PolitiFact, Cadegiani also said he had no conflict and reiterated that he had donated his payment.

The published version of the study simply stated that “all authors stated that they had no financial relationship at the present time or within the previous three years with any organizations that may have an interest in the submitted work” .

Brazil’s National Research Ethics Commission, meanwhile, is investigating another clinical trial of an experimental COVID-19 drug in which Cadegiani was lead author for a possible ethics violation, according to the BMJ and the publication Science.

Our decision

A post shared on Facebook about a study of ivermectin in Brazil states that “large peer-reviewed research study proves that ivermectin works”. The article is promoted by the Frontline COVID-19 Critical Care Alliance, a group that promotes the use of ivermectin to treat COVID-19. Two of the study’s authors are members of the group.

The study, said one of its authors, does not definitively prove that ivermectin works as a prevention or treatment for COVID-19.

Experts not involved in the study pointed to serious flaws in the study and conflicts of interest with its authors. The FDA and WHO have not changed their positions on the use of ivermectin outside of clinical trials.

We rate this claim as false.