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Editorials

Unethical studies of ivermectin for covid-19

BMJ 2022; 377 doi: https://doi.org/10.1136/bmj.o917 (Published 14 April 2022) Cite this as: BMJ 2022;377:o917
  1. Gideon Meyerowitz-Katz, epidemiologist1,
  2. Sarah Wieten, assistant professor2,
  3. María de Jesús Medina Arellano, researcher3,
  4. Gavin Yamey, professor of global health and public policy4
  1. 1School of Health and Society, University of Wollongong, Wollongong, New South Wales, Australia
  2. 2Department of Philosophy, Durham University, Durham, England
  3. 3Bioethics, Health and Biolaw Program, Instituto de Investigaciones Jurídicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
  4. 4Center for Policy Impact in Global Health, Duke Global Health Institute, Duke University, Durham, NC, USA
  1. Correspondence to: G Yamey gavin.yamey{at}duke.edu

Flawed research means we still do not know if the drug is safe or effective

During disease outbreaks, it can be tempting to sacrifice the scientific rigour of research in favour of speed, given the urgency to develop new treatments. After the 2014-16 Ebola outbreak in west Africa, however, a report on the ethics of research from the US National Academy of Medicine stated clearly that “research during an epidemic is still subject to the same core scientific and ethical requirements that govern all research on human subjects.”1 Early in the covid-19 pandemic ethicists warned researchers against “pandemic research exceptionalism”—lowering ethical standards because of the urgency of the crisis.2 Despite these warnings, there have been many examples of researchers treating covid-19 as exactly that: an exception to the rigorous standards to which we should hold medical research.3 There is no better example of such exceptionalism than the research into ivermectin for covid-19.

Ivermectin is used to treat a range of parasitic diseases, including onchocerciasis and helminthiases. On the basis of in vitro activity against SARS-CoV-2,4 the drug was tested as a possible treatment and prevention for covid-19. Initial randomised trials and systematic reviews suggested large benefits from the drug, including reduced hospital admissions and improved survival rates.56 It turns out that many of the results were—literally—too good to be true.7

An analysis of 26 major trials of ivermectin for covid-19 found that over one third had “serious errors or signs of potential fraud.”7 One prominent meta-analysis that suggested a large survival benefit from the drug was retracted.6 The authors did a re-analysis and found that the effect of ivermectin on survival that they had shown in their retracted study “was dependent on the inclusion of studies with a high risk of bias or potential medical fraud.”8 The editor of the American Journal of Therapeutics published an expression of concern about another high profile meta-analysis, noting suspicious data in several of the included studies and concluding that “exclusion of the suspicious data appears to invalidate the findings regarding ivermectin’s potential to decrease the mortality of covid-19 infection.”9

Ethics scandals

Two recent ethics scandals have cast a further shadow over ivermectin research. First, a report of an experimental study in Mexico City that gave almost 200 000 ivermectin based medical kits to residents with covid-19 was retracted from the preprint server SocArXiv.10 The report was retracted, says SocArXiv’s director, because the experiment was conducted “without proper consent or appropriate ethical protections.”11 Second, in an experiment in a jail in Arkansas, USA, four incarcerated men developed severe side effects after a physician gave them high dose ivermectin as a supposed covid-19 treatment without their knowledge.10 The four men are suing the jail.

Lack of consent was not the only ethical violation in these two scandals. The research participants were exposed to a risk of drug side effects without knowing they had been given ivermectin. In Mexico, the failure to give information to the participants infringed on a human right established in Mexico’s constitution: the right to access information.12 The Arkansas case raises additional concerns as it involved incarcerated people, who risk coercion and exploitation when they are enrolled in clinical research.

It is also arguably unethical and a waste of resources to conduct drug research in an emergency that is of such low quality that no conclusions can be drawn about the drug’s efficacy. That is the situation we find ourselves in today—it is still unclear whether ivermectin is safe or has any benefit in the treatment or prevention of covid-19.13 The flawed and potentially fraudulent research represents a huge missed opportunity to answer an important research question.

Abandoning research exceptionalism

The pressure to act quickly and do something instead of nothing in a global health emergency can lead researchers to cause harm or add to already existing injustices. But the answer is not to abandon research during crises, which could itself lead to “inadequate, ineffective, or even harmful care.”14 The answer is to abandon research exceptionalism.

Such exceptionalism is not needed to run fast, informative trials during a pandemic. The Recovery trial, for example, was a collaborative triumph that allowed clinicians quickly and efficiently to discard ineffective treatments such as lopinavir-ritonavir while adopting effective ones such as dexamethasone.1415 The trial started in March 2020 and released its first results in June 2020, finding an effective treatment for covid-19 just 10 weeks after enrolling the first participant while maintaining high ethical standards.16

The Nuffield Council on Bioethics has recommended several ways to conduct ethical research even under crisis conditions.17 These include research teams developing study protocols with input from the local community to ensure that a trial is acceptable. Research funders should require inclusive community engagement plans in all proposals and should collaborate with governments, national research institutions, and multilateral agencies at the start of an emergency to agree research priorities. Research ethics committees must consider “whether the proposed consent processes are the most appropriate and sensitive that they can be in the circumstances.”17 The urgency of a pandemic is never an excuse for poorly designed studies, ethical misconduct, or the violation of human rights.

Footnotes

  • Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following. GM-K has been involved in uncovering potentially fraudulent papers on ivermectin for covid-19. SW’s previous post-doctoral research centre received funding from the Arnold Foundation.

  • Provenance and peer review: Commissioned; not externally peer reviewed.

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References

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