Repositioned chloroquine and hydroxychloroquine as antiviral prophylaxis for COVID-19: A protocol for rapid systematic review of randomized controlled trials

  1. Raymond Chang
  2. Wei-Zen Sun

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Abstract

Since the SARS-CoV-2 outbreak rapidly evolved into a pandemic, there is an urgent need for rapid development, identification and confirmation of efficacious antiviral prophylaxis. In this setting, the existing drugs chloroquine (CQ) and hydroxychloroquine (HCQ) which has suggestive evidence of efficacy against SARS-CoV-2 infection and COVID-19 disease has become prime candidates to be repositioned as therapeutic and preventative agents, and a growing number of clinical trials have been registered to study their preventative potential for at-risk populations using a range of dosing schemes and outcome measures. This rapid systematic review protocol aims to provide streamlined and timely synthesis on methodologies and results of randomized controlled trials assessing the efficacy of CQ and HCQ in hopes that this will constructively inform further research as well as public health policy.

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  1. ScreenIT

    SciScore for 10.1101/2020.04.18.20071167: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    BlindingAdditionally, researchers intend to qualitatively summarize the risk of bias across different studies for each of six domains: (1) random sequence generation (2) allocation concealment (3) blinding methods (4) incomplete outcome data (5) selective outcome reporting (6) other biases, as referenced by the Cochrane collaboration network (Higgins et al., 2011).
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Additional corroborative searches will be executed using Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase, and without any language or publication status restrictions.
    Pubmed
    suggested: (PubMed, RRID:SCR_004846)
    Cochrane Central Register of Controlled Trials
    suggested: (Cochrane Central Register of Controlled Trials, RRID:SCR_006576)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    In order to identify articles that might have been missed in the electronic searches, we will a) scan the reference bibliographies of other pertinent systematic reviews on the search terms, and evaluate in full text all the articles they include, b) scan the reference lists of selected narrative reviews and other documents relevant to the subject, c) conduct cross-citation search in Google Scholar, as well as review relevant news websites in English and Chinese for any newly announced or unregistered trials.
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    Additionally, researchers intend to qualitatively summarize the risk of bias across different studies for each of six domains: (1) random sequence generation (2) allocation concealment (3) blinding methods (4) incomplete outcome data (5) selective outcome reporting (6) other biases, as referenced by the Cochrane collaboration network (Higgins et al., 2011).
    Cochrane
    suggested: (Cochrane Library, RRID:SCR_013000)
    Data synthesis and statistical analysis: If there are more than one trial and they are clinically homogeneous, we will conduct meta-analysis using RevMan 5.3
    RevMan
    suggested: (RevMan, RRID:SCR_003581)
    3 (Nordic Cochrane Centre, 2014), using the inverse variance method with random effects model.
    Cochrane Centre
    suggested: (ChiCTR - Chinese Clinical Trial Registry, RRID:SCR_006037)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.04.18.20071167 on medRxiv