Effects of tocilizumab on mortality in hospitalized patients with COVID-19: a multicentre cohort study

  1. Javier Martínez-Sanz
  2. Alfonso Muriel
  3. Raquel Ron
  4. Sabina Herrera
  5. José A. Pérez-Molina
  6. Santiago Moreno
  7. Sergio Serrano-Villar

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Abstract

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  1. ScreenIT

    SciScore for 10.1101/2020.06.08.20125245: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Ethics Committee at University Hospital Ramón y Cajal (ceic.hrc(at)salud.madrid.org, approval number 191/20).
    RandomizationThis assumption helped obtain a conservative estimate of the treatment hazard ratio analogous to intention-to-treat analysis in an unblinded randomized controlled trial.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    16.0 (StataCorp LP College Station, TX, USA).
    StataCorp
    suggested: (Stata, RRID:SCR_012763)
    Figures 1 and 2 were generated using Prism v.8.0 (GraphPad, La Jolla, California).
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    Our study has a number of limitations. As with any observational study, there is still a risk of unmeasured confounding. Tocilizumab targets the IL-6 receptor, and thus using baseline IL-6 levels instead of CRP in the interaction term with tocilizumab use could have helped to better discriminate the population benefiting most from tocilizumab treatment. Although IL-6 measurements are rarely available in clinical settings, CRP is widely accessible and is an inflammatory biomarker upstream of the IL-6 pathway.13 Hence, we doubt that the use of CRP instead of IL-6 limited the scope of the results. Ongoing trials of tocilizumab in COVID-19 have also considered heightened CRP instead of IL-6 to identify patients with heightened inflammation and, therefore, potential greater benefit with this treatment (clinicaltrials.gov: NCT04346355 and NCT04356937). In addition, the results should be interpreted cautiously and must not be taken as confirmatory of tocilizumab efficacy because of the relatively wide confidence intervals in the principal analysis. The sensitivity analyses suggested that patients with high CRP and high D-dimer levels or lymphopenia may also be target populations for tocilizumab use. However, despite the fact that the size effects observed here were consistent with those obtained in the principal analyses, the sub-analyses must only be interpreted as exploratory and hypothesis-generating. The main strengths of the study include the large sample size and multicenter c...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04346355TerminatedEfficacy of Early Administration of Tocilizumab in COVID-19 …
    NCT04356937CompletedEfficacy of Tocilizumab on Patients With COVID-19

    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 10.1016/j.cmi.2020.09.021
  3. ScreenIT

    SciScore for 10.1101/2020.06.08.20125245: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementThis study was approved by the Ethics Committee at University Hospital Ramón y Cajal (ceic.hrc@salud.madrid.org, approval number 191/20).RandomizationThis assumption helped obtain a conservative estimate of the treatment hazard ratio analogous to intention-to-treat analysis in an unblinded randomized controlled trial.Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    16.0 ( StataCorp LP College Station , TX , USA) .
    StataCorp
    suggested: (Stata, SCR_012763)
    Figures 1 and 2 were generated using Prism v .8.0 ( GraphPad , La Jolla , California) .
    Prism
    suggested: (PRISM, SCR_005375)
          <div style="margin-bottom:8px">
        <div><b>GraphPad</b></div>
        <div>suggested: (GraphPad Prism, <a href="https://scicrunch.org/resources/Any/search?q=SCR_002798">SCR_002798</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">S.M. reports grants, personal fees and non-financial support from ViiV Healthcare, personal fees and non-financial support from Janssen, grants, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from Gilead, outside the submitted work.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>ViiV Healthcare</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr></table>

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

    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2020.06.08.20125245v1 on medRxiv