Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

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  1. Venkata Emani, Nidhi K. Reddy, Kartik Goswami, Raghunath Reddy, Dheeraj Nandanoor, Sanjeev Goswami

    Review 1: "Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial"

    Reviewers: Venkata Emani, Nidhi K. Reddy, Kartik Goswami, Raghunath Reddy, Dheeraj Nandanoor, Sanjeev Goswami (Central Valley Cardiovascular Associates) | 📒📒📒 ◻️◻️

  2. Venkata Emani, Nidhi K. Reddy, Kartik Goswami, Raghunath Reddy, Dheeraj Nandanoor, Sanjeev Goswami

    Review of "Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial"

    Reviewers: Venkata Emani, Nidhi K. Reddy, Kartik Goswami, Raghunath Reddy, Dheeraj Nandanoor, Sanjeev Goswami (Central Valley Cardiovascular Associates) | 📒📒📒 ◻️◻️

  3. SciScore for 10.1101/2021.02.11.21249258: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The trial is conducted in accordance with the principles of the International Conference on Harmonisation–Good Clinical Practice guidelines and approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the Cambridge East Research Ethics Committee (ref: 20/EE/0101).
    Consent: Written informed consent was obtained from all patients, or their legal representative if they were too unwell or unable to provide consent.
    RandomizationPatients who were eligible for randomisation to tocilizumab were assigned to either usual standard of care or usual standard of care plus tocilizumab in a 1:1 ratio using web-based simple (unstratified) randomisation with allocation concealed until after randomisation.
    Blindingnot detected.
    Power AnalysisPrior to commencement of the randomisation to tocilizumab vs. usual care, the trial steering committee determined that if 28-day mortality in the usual care group was above 25% then recruitment of around 4000 patients to this comparison would provide 90% power at two-sided P=0.01 to detect a proportional reduction in 28-day mortality of one-fifth.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    either convalescent plasma or REGN-COV2 (a combination of two monoclonal antibodies directed against SARS-CoV-2 spike protein); and part 3, no additional treatment vs. aspirin.
    REGN-COV2
    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:
    There are some limitations: For this preliminary report, information on the primary outcome is available for 92% of patients. This should increase to >99% by early March when all patients have passed the 28-day follow-up period. Following random assignment, 17% of patients in the tocilizumab group did not receive this treatment. The reasons for this were not recorded. The size of the effects of tocilizumab reported in this paper are therefore an underestimate of the true effects of actually using the treatment. Hospital stay is very long for many of these patients (median >28 days); the pre-planned analyses at 6 months will provide additional information on the full effects of tocilizumab on clinical outcomes. The RECOVERY results support the use of tocilizumab, but other IL-6 antagonists are available. Although the effects of sarilumab in REMAP-CAP were similar to tocilizumab, only 48 participants received sarilumab.8 Two larger trials of sarilumab have completed but have not reported any results (NCT044327388, NTC044315298). Publication of results from those trials is now essential to assess whether alternative IL-6 antagonists to tocilizumab are effective. Guidelines on the use of IL-6 antagonists for patients with severe COVID-19 vary. For example the US National Institutes for Health conclusion is that there are insufficient data to recommend either for or against the use of tocilizumab or sarilumab, a view shared by some commentators.19,20 By contrast, interim guidance ...

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

    IdentifierStatusTitle
    NCT04381936RecruitingRandomised Evaluation of COVID-19 Therapy
    NCT044327388Trial number did not resolve on clinicaltrials.gov. Is the number correct?NA


    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 scite Reference Check: We found no unreliable references.


    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.