Tocilizumab in Hospitalized Patients with COVID-19: A Meta Analysis of Randomized Controlled Trials

  1. Vijairam Selvaraj
  2. Mohammad Saud Khan
  3. Chirag Bavishi
  4. Kwame Dapaah-Afriyie
  5. Arkadiy Finn
  6. Amos Lal
  7. Eleftherios Mylonakis

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Abstract

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  1. Version published to 10.1007/s00408-021-00451-9
  2. ScreenIT

    SciScore for 10.1101/2021.03.23.21254054: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationA study was considered eligible for inclusion in the analysis if it was 1) randomized controlled trial 2) reported outcomes of interest in hospitalized COVID-19 patients with tocilizumab therapy compared to standard treatment or placebo.
    BlindingThis methodology explores the adequacy of sequestration, allocation sequence concealment, blinding of participants and study personnel, blinding for outcome assessment, incomplete outcome or selective outcome reporting, and another potential bias.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data Sources and Search Strategy: This study was conducted according to the Cochrane Collaboration and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement [30].
    Cochrane Collaboration
    suggested: None
    We conducted a systematic search in MEDLINE, EMBASE, Cochrane Central and preprint databases to identify all relevant articles using the following search terms: (“SARS-CoV2” OR “COVID-19”) AND (“tocilizumab” OR “IL6” OR “Anti-IL6”).
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)
    All results were imported into EndNote x8.2 (Clarivate Analytics) and duplicate results were identified and removed.
    EndNote
    suggested: (EndNote, RRID:SCR_014001)
    Statistical analysis was performed using Review Manager, version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).
    Review Manager
    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: We detected the following sentences addressing limitations in the study:
    One of the limitations of the meta-analysis is integral to the methodology. The summarization of information may ignore the important difference between studies. Secondly, the number of patients in the RECOVERY trial was much higher than other RCTs (study weight 77%) [33]. There were differences in enrollment criteria, the time at which anti–interleukin-6 therapy was initiated, the primary outcome, and background care. Also, five of the included studies had an open label design, implying high risk of performance and selection bias due to lack of blinding of participants and personnel to intervention, limiting our ability to interpret results. Lastly, we included one trial from the preprint databases, which has not been peer-reviewed [33]. Preprint articles possibly indicate the undetermined quality of available literature. One of the trials also ended early due to safety concerns, although mortality in the control arm was extremely low [29]. In conclusion, our meta-analysis suggests tocilizumab, when used along with dexamethasone, could be an effective therapeutic option with promising evidence on reduced mortality, progression to mechanical ventilation, and discharge from hospital. Limitations may exist in terms of obtaining tocilizumab as it is an expensive monoclonal antibody. Supplies may be limited, and many hospitals may not necessarily have adequate quantities. Clinical judgement is also necessary as some patients may not require the use of tocilizumab. Future studies ...

    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.

  3. Version published to 10.1101/2021.03.23.21254054v1 on medRxiv