Fact Check-Gaps in study claiming that ivermectin reduces risk of COVID-19 death by 92%

Social media users are sharing a report about a Brazilian study that claims regular use of ivermectin reduces the risk of death from COVID-19 by 92%.

Examples can be seen (here) and (here).

The text in one post reads: “Peer-reviewed study of 88,000 people finds ‘Ivermectin reduces COVID death risk by 92%’ But, but… horse de-wormer! At what point will the ‘COVID conspiracy theorists’ be remembered as the only adults in the room?” Comments on the posts include: “And the American people knew all along that it worked but we were not allowed to have it!”, “Those of us that are awake have known this for over a year!” and “Less death was NOT what they wanted.”

Some users commented on the posts that the National Institutes of Health (NIH) has “silently approved” ivermectin. Reuters previously debunked this claim (here). As of September 2022, the NIH recommends “against the use of ivermectin for the treatment of COVID-19, except in clinical trials” (here), as does the World Health Organization (here).

Ivermectin is used to treat a wide range of diseases caused by parasites, such as River Blindness and strongyloidiasis in humans (here)

The new study, based on data from a voluntary program offering preventive ivermectin in a small Brazilian city early in the pandemic, claims that regular ivermectin use was associated with better protection from COVID-19 infection and “related outcomes” such as death. But scientists say there are too many gaps in the paper to draw conclusions about whether ivermectin had an effect.

STUDY FINDINGS

The study, “Regular Use of Ivermectin as Prophylaxis for COVID-19 Led Up to a 92% Reduction in COVID-19 Mortality Rate in a Dose-Response Manner: Results of a Prospective Observational Study of a Strictly Controlled Population of 88,012 Subjects,” was published (here) on Aug. 31, 2022, by the online journal Cureus.

The authors analyzed data on participants in a voluntary citywide program in Itajaí, southern Brazil, that offered ivermectin as a preventive measure against COVID-19 between July and December of 2020.

Participants in the program were prescribed ivermectin for two consecutive days, every 15 days, for 150 days. The study team did not have information about how much medication individuals really took; instead, they categorized “regular users” as those who received a total of 180 mg (30 tablets) or more of the drug from the program over the entire period, versus “irregular users” who received up to 60 mg (10 tablets) during the study period.

The study initially identified 159,560 adults over age 18 as eligible for inclusion in the analysis. The authors then excluded more than 71,000 of these people whose ivermectin use was considered “intermediate” – those having received between 60 mg and 180 mg – with the explanation that this would make for a clearer comparison between “regular” and “irregular” users.

That narrowed the study population to 8,325 “regular” ivermectin users and 33,971 “irregular” users. These were compared with 45,716 other city residents not prescribed ivermectin, for a total of 88,012 people included in the study.

However, several calculations for COVID-19 outcomes were based on comparisons of much smaller sets of 283 individuals from each ivermectin-use group, matched according to age and certain health conditions such as diabetes and asthma.

For example, the apparent 92% reduction in risk of dying from any cause – not only from COVID — for regular ivermectin users was based on the finding that 15 of 283 ivermectin non-users died during the study period as compared with 2 of 283 regular users.

A different analysis in the paper found an apparent reduction in COVID-specific mortality of 86% among regular ivermectin users versus non-users.

As an observational study, the results cannot prove that ivermectin is the reason for apparent reductions in risk of death from any cause or from COVID-19 specifically (here). But the study is also missing certain types of data needed to support its conclusions, experts said.

DATA LACKING

First, in addition to being unable to confirm whether ivermectin users actually took all the medication they received from the program, the authors acknowledge but do not factor-in the possibility that people identified as non-users or irregular users could have acquired the drug outside the city’s program and taken it on their own.

Dr. Stuart Ray, professor of medicine at the Johns Hopkins University School of Medicine, told Reuters via email that “the accuracy of inferred ivermectin use seems to be low based on reports from the local health authorities in Brazil that many people took ivermectin who were not prescribed, and many who were prescribed ivermectin did not take it.”

Second, the study doesn’t account for other possible differences between the groups that could introduce bias in the calculations.

“The main shortcoming here is that the program was optional – and we know well from decades of literature, that those who choose to seek healthcare and take medicines are inherently different from those who do not,” Dr. Mark Siedner, an infectious disease clinician and clinical epidemiologist at Massachusetts General Hospital, told Reuters via email.

“There are also a number of additional shortcomings that have to do with missing data,” Seidner said. Referring to the 71,548 “moderate” users of ivermectin excluded from the analysis entirely, as well as the calculations based on small matched subsets of 283 people, he noted, “for example, almost half the sample appears to have been excluded and nearly 99% was excluded in their analysis that included age and health problems, and there is no good way of accounting for infection rates in people who were never tested.”

The study authors do acknowledge that they could have missed some hospitalizations, deaths, and COVID-19 infections that were not reported in the datasets they used.

In response to online criticisms of the study’s methods, the editor of Cureus told Retraction Watch that, “This article was carefully reviewed and not found to have any substantial methodological flaws.” (here). The study’s corresponding author, Flavio A. Cadegiani, responded to a Reuters request for comment that he also stands by the study’s methods and results.

The current study does disclose extensive relationships between its authors and groups with an interest in promoting ivermectin, Ray noted. “The Disclosures section of the article reveals that multiple authors including the lead author have financial or consulting relationships with a company that manufactures ivermectin and groups that have a long history of promoting its use. Such conflicts do not invalidate a study, but they do represent potential conflict of interest, and the study’s weak scientific methods don’t mitigate these concerns,” Ray said.

IVERMECTIN AND COVID-19 – WHAT WE KNOW

“There was some initial hope for ivermectin based on test tube studies of very high concentrations of ivermectin that are not safely achievable with standard dosing; still, scientists performed rigorous randomized clinical trials and those revealed no signs of ivermectin efficacy against COVID-19 in people,” Ray said.

“The current study by Kerr et al. is too flawed and subject to bias to change the current understanding – ivermectin is excellent for its approved indications but it doesn’t improve COVID-19 outcomes when carefully studied,” he explained.

Randomized controlled trials, the gold standard for medical evidence, have repeatedly found no effect on COVID-19 outcomes with use of ivermectin (here) (here) (here).

Observational studies like the one from Brazil help generate new ideas but do not provide the evidence required to make clinical or public health recommendations, Seidner said. “In light of so much better data showing ivermectin is not helpful, even in the early stages of COVID-19, the findings of this study should not be used for much more than to potentially encourage a better study to be done to explore its safety and benefit as a prevention agent.”

VERDICT

Misleading. An observational study based on data from a Brazilian city offering prophylactic ivermectin early in the SARS-CoV-2 pandemic finds an apparent reduction in deaths from all causes and from COVID-19 specifically among some ivermectin users, but the study lacks several types of relevant data and fails to account for potential confounding factors.

This article was produced by the Reuters Fact Check team. Read more about our fact-checking work  here  .