Comparing the efficacy of anti□infectious drugs for the treatment of mild to severe COVID-19 patients: a protocol for a systematic review and network meta-analysis of randomized clinical trials

  1. Dejene Tolossa Debela
  2. Kidist Digamo Heraro

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Abstract

Background

COVID-19 is a viral infection spreading at a great speed and has quickly caused an extensive burden to individuals, families, countries, and the world. No intervention has yet been proven highly effective for the treatment of COVID-19. Different drugs were being evaluated and reported through randomized clinical trials, and more are currently under trial. This review aimed to compare the efficacy of anti-infectious drugs with a comparator of the standard of care or placebo in patients with COVID-19.

Methods and analysis

Two independent review authors will extract data and assess a risk of bias using RoB2. Randomized controlled trials (RCT) that evaluate single and/or combined antiviral drugs recommended by WHO latest guideline for the treatment of COVID-19 will be included. We will search for Pub Med, the Cochrane Center for Clinical Trial database (CENTRAL), clinicaltrials.gov, etc. databases for articles published in the English language between December 2019 to April 2021. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) involving Network Meta-analysis guidelines for the design and reporting of the results. The primary endpoints will be time to clinical recovery and time to RNA negativity. The certainty of evidence will be evaluated using the GRADE extension of NMA. Data analysis will be performed using the frequentist NMA approach with netmeta package implemented in R.

Ethics and dissemination

There are no ethical considerations associated with this study as we will use publicly available data from previously published studies. We plan to publish results in open access peer-reviewed journals.

PROSPERO registration number

ID=CRD42021230919.

Strengths and limitations of this study

  • This will be the first systematic review and network meta-analysis to assess the efficacy specific to anti-infectious drugs category for for mild to severe patients of COVID-19.

  • Its compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols (PRISMA-P) involving network meta-analysis(NMA) will ensure the quality of reporting.

  • Doing both pairwise meta-analysis and network meta-analysis (NMA) can comprehensively analyse direct and indirect comparison results of different anti-infectious drugs for COVID 19 will give more reliable conclusions aswell as the rank of those drugs.

  • There is risk of heterogeneity and inconsistency, given the different anti-infectious drugs that will be included; however, we try to control intransitivity by carefully identifying the eligibility criteria depending on PICOS strategy and assess inconsistency using local as well as global approaches.

  • The limitation of this study is it will not explore the economic benefits of these drugs.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.19.21253957: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We will conduct search for PubMed, the Cochrane Center for Clinical Trial database (CENTRAL), clinicaltrials.gov, clinicaltrialsregister.eu, chictr.org.cn, covid-19.cochrane.org, and covid-evidence.org. databases for articles published worldwide in the English language.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Cochrane Center for Clinical Trial
    suggested: None
    The search will be done according to guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions.
    Cochrane Handbook
    suggested: None
    Eligibility criteria: We will identify eligible studies through the PICOS(participants, interventions, comparison, outcomes, and study designs) format(21) Selection of studies: Endnote software version X7 will be used to import the research articles from the electronic databases and duplicates will be removed.
    Endnote
    suggested: (EndNote, RRID:SCR_014001)
    Assessment of risk of bias: The risk of bias assessment will be based on the Cochrane Risk of Bias tool version 2 (Rob 2) as recommended in The Cochrane Handbook of Systematic Reviews of Interventions(22).
    Cochrane Risk of Bias
    suggested: None

    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 10.1101/2021.03.19.21253957v1 on medRxiv