key: cord-0797828-jbkz0pm0
authors: Banno, Masahiro; Tsujimoto, Yasushi; Ishikane, Masahiro
title: Need for More Randomized Controlled Trials With Rigorous Methodology to Confirm That Ivermectin Is Not a Viable Option for the Treatment of Coronavirus Disease 2019
date: 2021-08-06
journal: Clin Infect Dis
DOI: 10.1093/cid/ciab689
sha: e6c586ded082607232c5efcc541b7e8ae30c54b8
doc_id: 797828
cord_uid: jbkz0pm0

nan

To the Editor-We read with interest the study by Roman et al, in which they performed a systematic review and metaanalysis of randomized controlled trials (RCTs) to evaluate the effect of ivermectin on all-cause mortality in patients with coronavirus disease 2019 (COVID-19) [1] . We appreciate the authors' hard work in advancing our knowledge in this field; however, we have some concerns about their article.

First, their conclusions diverged from the results in the abstract. Based on the Grading of Recommendations, Assessment, Development, and Evaluations approach used in this review, the interpretation should have been that the evidence regarding the effect of ivermectin on all-cause mortality is uncertain [2] . However, the authors strongly expressed the conclusion that ivermectin did not reduce the all-cause mortality, length of stay, or viral clearance in the COVID-19 patients compared with controls and that ivermectin is not a viable option. This could potentially mislead the readers. It would be better if the authors stated that more RCTs with rigorous methodology are needed to confirm that ivermectin is not a viable option for the treatment of COVID-19.

Second, the literature search was not comprehensive. Their review did not include 11 RCTs and 39 ongoing trials, which were described in the study by Bryant et al [3] . The reason for the low retrieval of existing evidence could be that they did not search trial registries such as the International Clinical Trials Registry Platform and ClinicalTrials.gov [4, 5] .

Third, the protocol used in the study is not available anywhere. We agree with their selection of outcomes and statistical models that produced a conservative confidence interval. However, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement, the protocol should be registered to prevent unnecessary concerns about bias in the selection of the results [6, 7] . Therefore, we would encourage the authors to interpret their results carefully in line with the certainty of evidence and acknowledge the limitations of the methodology.

Ivermectin for the treatment of COVID-19: a systematic review and meta-analysis of randomized controlled trials

GRADE Working Group. GRADE guidelines 26: informative statements to communicate the findings of systematic reviews of interventions

Ivermectin for prevention and treatment of COVID-19 infection: a systematic review, meta-analysis, and trial sequential analysis to inform clinical guidelines

Studies registered in non-ClinicalTrials.gov accounted for an increasing proportion of protocol registrations in medical research

Cochrane handbook for systematic reviews of interventions version 6.2. 2021

PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews

Available at: https:// training.cochrane.org/resource/rob-2-domain-5-bias-selection-reported-result