Ivermectin and the study of Itajai, Brazil

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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

The above was a retrospective analysis of data from July to December 2020 in a clinical database for a COVID-19 prevention program implemented in the Brazilian city of Itajaí.

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Original article

peer-reviewed

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

Lucy Kerr, Fernando Baldi, Raysildo Lobo, Washington Luiz Assagra, Fernando Carlos Proença, Juan J. Chamie, Jennifer A. Hibberd, Pierre Kory, Flavio A. Cadegiani


Published: August 31, 2022 (see history)

DOI: 10.7759/cureus.28624

Cite this article as: Kerr L, Baldi F, Lobo R, et al. (August 31, 2022) 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. Cureus 14(8): e28624. doi:10.7759/cureus.28624

Abstract

Background

We have previously demonstrated that ivermectin used as prophylaxis for coronavirus disease 2019 (COVID-19), irrespective of the regularity, in a strictly controlled citywide program in Southern Brazil (Itajaí, Brazil), was associated with reductions in COVID-19 infection, hospitalization, and mortality rates. In this study, our objective was to determine if the regular use of ivermectin impacted the level of protection from COVID-19 and related outcomes, reinforcing the efficacy of ivermectin through the demonstration of a dose-response effect.
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Conclusion

Non-use of ivermectin was associated with a 12.5-fold increase in mortality rate and a seven-fold increased risk of dying from COVID-19 compared to the regular use of ivermectin. This dose-response efficacy reinforces the prophylactic effects of ivermectin against COVID-19.


https://www.cureus.com/articles/111851-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-88012-subjects

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DETAILS

Overstates scientific confidence: The study contained multiple methodological flaws that call the reliability of its conclusions into question. For example, there are indications that many people assigned to the ivermectin treatment group didn’t take the drug consistently, or stopped taking it after a while. It is therefore unclear whether any observed effect in this group can be reliably attributed to ivermectin treatment.

KEY TAKE AWAY

Ivermectin is a drug used to treat parasitic infections in humans and animals. Although some studies conducted on cells growing in the lab suggest that ivermectin has antiviral properties, reliable and large-scale clinical trials in humans haven’t detected significant benefits from ivermectin treatment in COVID-19 patients so far. At the moment, scientists are continuing to study ivermectin in order to explore its potential as a COVID-19 treatment.

FULL CLAIM: A preprint of an ivermectin study in the Brazilian city of Itajaí found that prophylactic ivermectin reduced COVID-19 hospitalization and mortality by half

REVIEW

The drug ivermectin has become a breeding ground for conflict during the COVID-19 pandemic. Ivermectin is a derivative of avermectin, a naturally-occurring compound discovered by William Campbell and Satoshi Omura, which won them the Nobel Prize for Physiology or Medicine in 2015. Used to treat parasitic infections in humans and animals, an in vitro study and a study in hamsters in 2020 suggested that the drug could have beneficial effects in fighting SARS-CoV-2 infection[1,2], prompting scientists to study the drug for its potential as a COVID-19 treatment.
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Briefly, the preprint in question was a retrospective analysis of data from July to December 2020 in a clinical database for a COVID-19 prevention program implemented in the Brazilian city of Itajaí. The aim of the study was to determine the effects of prophylactic (preventative) ivermectin on the risk of infection, hospitalization, and mortality. To do this, the authors compared the disease outcomes (infection and mortality) in more than 133,000 people who used ivermectin with that of more than 87,000 people who didn’t. A person was considered to be an ivermectin user if they opted into the program.

For example, despite the authors’ claim to have controlled for all relevant confounding factors in the study, Meyerowitz-Katz pointed out that they didn’t account for confounding factors influencing risk of infection, like occupation and income, despite being a study examining ivermectin’s effect on risk of infection. 

Confounding factors are variables that affect the outcome of an experiment, but aren’t the variables being studied in the experiment. For example, scientists may wish to study the causes of heart disease. They may observe that red meat consumption is associated with a higher risk of heart disease. But it is possible that people who tend to eat more red meat might also be more likely to smoke cigarettes. In such a case, one possible explanation for the observation is that cigarette smoking, rather than red meat consumption, is the true influence behind that risk. This makes cigarette smoking a confounding factor.

The above example illustrates how failing to account for such confounding factors can lead scientists to draw erroneous conclusions about the cause of an effect that they observe in the study.
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In addition, it’s unknown how many people in both groups had already been taking ivermectin before the study. It’s also unknown whether people who were part of the ivermectin treatment group had consistently taken the drug throughout the study. In fact, there are indications that many who had initially started the ivermectin treatment didn’t continue the treatment. This raises questions about whether any effects seen in the ivermectin treatment group can be reliably attributed to ivermectin in the first place. Indeed, it’s unknown whether the improvement observed in the treatment group would still remain if people who didn’t actually take ivermectin were removed from that group and the data re-analyzed.
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Interestingly, the authors acknowledged this issue in the Discussion: “Due to the large number of participants, this citywide program was unable to supervise whether ivermectin users were using ivermectin regularly, in the correct dose and interval proposed.” But they didn’t fully account for its potential effects on their findings, instead simply suggesting that their findings underestimated ivermectin’s beneficial effects, implying that the true benefit was even larger. While that is one possibility, the authors didn’t appear to consider how the problems above may have also obscured a potential absence of benefit or even harm from ivermectin treatment. There isn’t evidence to support the a priori assumption that ivermectin treatment can only lead to improvement.

In his concluding remarks, Meyerowitz-Katz called it “a very weak observational study” that gave us “no useful information at this point in the ivermectin literature”:
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It’s also of note that Itajaí actually saw the highest COVID-19 mortality rate in 2020 among the major cities in the state of Santa Catarina, another observation that casts doubt over whether the COVID-19 prevention program using ivermectin was actually effective.

Finally, at least two of the authors, Flavio Cadegiani and Juan Chamie, are members of a group called the Front Line COVID-19 Critical Care Alliance (FLCCC). This group, led by physicians Pierre Kory and Paul Marik, propagated unsupported claims about ivermectin as an effective COVID-19 treatment. Cadegiani is also the principal investigator of a clinical trial that is being investigated for potential violations of medical ethics and human rights by Brazil’s National Health Council, as reported by the British Medical Journal. Cadegiani and Lucy Kerr also have financial conflicts of interest from their work for a company that produces ivermectin.
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UPDATE (25 Jan. 2022):

We updated the review to indicate that the preprint by Kerr et al. has since been published in the scientific journal Cureus (see here).

https://healthfeedback.org/claimreview/ivermectin-study-itajai-contains-methodological-weaknesses-questionable-conclusions/

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Study in Brazil on ivermectin as a COVID-19 prevention is flawed, experts say

By Jeff Cercone January 28, 2022

If Your Time is short

  • Experts we spoke with point out serious flaws in the study’s methodology and conclusions.
  • Health officials in Itajaí said that most residents they initially distributed the drug to did not take all five doses as recommended.
  • The FDA and World Health Organization still do not recommend the use of ivermectin in treating or preventing COVID-19 outside of clinical trials.
  • One of the study’s authors said ivermectin seemed to work  at preventing COVID-19, but he never said it was “proven.”

See the sources for this fact-check

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Concerns about methodology

Dr. Nikolas Wada, an epidemiologist with the Novel Coronavirus Research Compendium at Johns Hopkins, raised concerns about the study’s uncertainty over who was “truly taking ivermectin and vice versa” and poor control for factors that may predispose someone to catch COVID-19, among other issues.

“My primary takeaway,” Wada said, “is that this paper adds nearly 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 Ph.D student from the University of Wollongong in Australia who often writes about COVID-19, said the research lacks critical information about the study’s participants, including how many Itajaí residents were already taking ivermectin before the program began and how many continued to take the full doses of the drug as prescribed.

“This sort of epidemiological study is very prone to biases resulting from characteristics that are inherently different between the intervention and control groups,” Meyerowitz-Katz said. “There is essentially no information on how many people in either the intervention or control group actually took ivermectin, which is a fairly important consideration if that’s what the authors were trying to 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 draft version that has not been peer-reviewed. 

He said not much has changed in the published version.

The Municipal Health Department of Itajaí said in January of 2021 — a year before the study was published — that 138,216 residents took the first dose of ivermectin when it started distributing the drug as part of a citywide 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.
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Our ruling

An article shared on Facebook about an ivermectin study out of Brazil states that the “large, peer-reviewed research study proves ivermectin works.” The article is being promoted by the Front Line 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, one of its authors said, does not definitively prove that ivermectin works as a prevention or treatment for COVID-19.

Experts not involved in the study pointed out 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 False.

https://www.politifact.com/factchecks/2022/jan/28/facebook-posts/study-brazil-ivermectin-covid-19-prevention-flawed/

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