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.
‘Undercooked’ COVID-19 research, such as those relating to ivermectin, has done considerable harm. They have fuelled incredible claims about treatments/cures/protection without scientific evidence as to efficacy and safety. They have fed into dodgy claims by politicians, media figures and other influencers.
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errors or signs of potential fraud.”7 One prominent meta-analysis that suggested a large survival benefit from the drug was retracted.6 The authors did a re-analysis and found that the effect of ivermectin on survival that they had shown in their retracted study “was dependent on the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
References
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Integrating clinical research into epidemic response: the Ebola experience.National Academies Press, 2017.
National Academies of Sciences, Engineering, and Medicine.
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Against pandemic research exceptionalism. Science2020;368:476–7.doi:10.1126/science.abc1731 pmid:32327600
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Review of: “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial Gautret et al 2010, DOI:10.1016/j.ijantimicag.2020.105949. Int J Antimicrob Agents2020;56:106063.doi:10.1016/j.ijantimicag.2020.106063 pmid:32674928
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Ivermectin for prevention and treatment of COVID-19 infection: a systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines. Am J Ther2021;28:e434–60.doi:10.1097/MJT.0000000000001402 pmid:34145166
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Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection[Retracted]. Open Forum Infect Dis2021doi:10.1093/ofid/ofab358
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Schraer R, Goodman J. Ivermectin: how false science created a covid “miracle” drug. BBC News 2021 Oct 6. https://www.bbc.co.uk/news/health-58170809
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Ivermectin for COVID-19: addressing potential bias and medical fraud. Open Forum Infect Dis2022;9:b645. doi:10.1093/ofid/ofab645 pmid:35071686
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. Expression of concern for Bryant A, Lawrie TA, Dowswell T, Fordham EJ, Mitchell S, Hill SR, Tham TC. Ivermectin for prevention and treatment of COVID-19 Infection: a systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines. Am J Ther2022;29:e232. doi:10.1097/CND.0000000000000400 pmid:35142702 CrossRefPubMedGoogle Scholar
Publisher (Open Access): https://www.bmj.com/content/377/bmj.o917