key: cord-1018072-9ykjod6w
authors: Kumar, Jogender; Jain, Siddharth; Yadav, Arushi; Meena, Jitendra
title: Efficacy and Safety of Hydroxychloroquine/chloroquine against SARS-CoV-2 Infection: A Systematic Review and Meta-analysis – Authors Reply
date: 2021-07-16
journal: J Infect Chemother
DOI: 10.1016/j.jiac.2021.07.010
sha: cdab59d25edfc55927b0830b9dc68bdfd2dd34ff
doc_id: 1018072
cord_uid: 9ykjod6w

nan

We appreciate the Boglione and colleagues' [1] interest in our meta-analysis on the efficacy and safety of hydroxychloroquine (HCQ) in patients affected by COVID-19 [2] . We want to take this opportunity to clarify the points raised by them.

1. The authors raised a point over criteria used to define the disease severity. They rightly pointed that the severity criteria might be different across the studies. We agree over it and already mentioned the lack of clear definitions and separate data for different disease categories in trials.

2. The authors suggested a meta-regression for the effect of disease severity (using the P/F values at the admission), HCQ dose, and duration of treatment on efficacy and safety of HCQ. The suggestion is reasonable but not feasible given the limited studies for various outcomes and their data. For example, most studies did not report the P/F value or other criteria used to define disease severity. Furthermore, as a thumb rule, to ensure adequate statistical power, a minimum of ten studies are required to test one covariate in metaregression analysis [3, 4] . Unfortunately, neither of these criteria were met, therefore precluding any meta-regression analysis.

3. We excluded the study by Catteau L et al. [5] as it was a retrospective study, and we have predefined criteria for excluding retrospective studies as there are at high risk of biases.

Furthermore, we have seen that premature conclusions from retrospective studies did not hold in rigorous randomized trials in this pandemic. The same holds for this study too. Therefore, we decide a priori to exclude retrospective studies.

period [6] . Therefore, in our opinion best approach in such a scenario would have been to do a meta-regression using cumulative dosage as a moderator (which takes both dose and duration into account). Unfortunately, that was not possible in this review due to a limited number of studies (as mentioned earlier). As many more trials have been published after this meta-analysis, exploring this aspect in further meta-analyses might be possible.

Response to: Efficacy and safety of hydroxychloroquine/chloroquine against SARS-CoV-2 infection: a systematic review and meta-analysis

Efficacy and safety of hydroxychloroquine/chloroquine against SARS-CoV-2 infection: A systematic review and meta-analysis

Methodological Standards for Meta-Analyses and Qualitative Systematic Reviews of Cardiac Prevention and Treatment Studies: A Scientific Statement From the American Heart Association

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Lowdose hydroxychloroquine therapy and mortality in hospitalised patients with COVID-19: a nationwide observational study of 8075 participants