Comparative effectiveness and safety of antiviral agents for patients with COVID-19: Protocol for a systematic review and individual-patient data network meta-analysis

Abstract

Background A recent cluster of pneumonia cases in Wuhan, China, has been caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We propose the protocol described below to perform an individual-patient data (IPD) network meta-analysis (NMA) in order to evaluate the efficacies of different antiviral drugs to treat patients with coronavirus disease 2019 (COVID-19). Materials and methods We will search the Medline, EMBASE, Cochrane Library, SinoMed, CNKI and VIP databases from their inceptions through July 2020. There will be no restrictions on language, publication year, or publication type. Randomized clinical trials (RCTs) and prospective cohort studies with antiviral treatments for COVID-19 will be considered. Two reviewers will independently select studies and collect data. Risk-of-bias assessments will be completed using the Cochrane risk-of-bias scale. Primary outcome will be the COVID-19 recovery rate. We will combine aggregated data from IPD with the NMA in a single model, compare the effects of different antiviral drugs on patient-relevant efficacy, and rank the results to decide which is the most effective. Trial registration PROSPERO registration number: CRD42020167038.

Hydroxychloroquine/chloroquine for the treatment of hospitalized patients with COVID-19: An individual participant data meta-analysis

“…39,41,42 We are aware of only 4 additional published IPD meta-analyses for COVID-19 therapeutics (3 planned; 1 smaller one completed). [43][44][45][46] Two metaanalyses planned to use IPD data to supplement aggregate data but could not obtain them. 41,47 At least 50 aggregate data meta-analyses evaluating HCQ/CQ in hospitalized COVID-19 patients have been published, with the overwhelming majority finding lack of evidence of convincing clinical benefit, and many finding worse clinical outcomes and increased AE rates.…”

“…39,41,42 We are aware of only 4 additional published IPD meta-analyses for COVID-19 therapeutics (3 planned; 1 smaller one completed). 43–46 Two meta-analyses planned to use IPD data to supplement aggregate data but could not obtain them. 41,47…”

“…To our knowledge, this is the first published meta-analysis of HCQ/CQ trials in hospitalized COVID-19 patients to use IPD rather than aggregate data. We are aware of only 4 additional published IPD meta-analyses for COVID-19 therapeutics (3 planned; 1 smaller one completed) [41][42][43][44]. Two meta-analyses planned to use IPD data to supplement aggregate data but could not obtain them [45,46].…”

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COVID-19 individual participant data meta-analyses. Can there be too many? Results from a rapid systematic review

“…One IPD-MA was limited to studies in the US and Canada, [27] another to the US, Europe, and China, [28] and one to China. [29] Treatment or exposure Sixteen IPD-MAs focused on the evaluation of medical treatments, including antivirals (n=6), [13,16,[29][30][31][32] antibodies (n=4), [19,24,33,34] angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs; n=2), [27,35] convalescent plasma (n=2), [36,37] COVID-19 vaccines (n=1), [38] and the Bacillus Calmette-Guérin (BCG)-vaccine (n=1). [26] One IPD-MA focused on extracorporeal membrane oxygenation (ECMO).…”