Effect of hydroxychloroquine with or without azithromycin on the mortality of coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis

  1. Thibault Fiolet
  2. Anthony Guihur
  3. Mathieu Edouard Rebeaud
  4. Matthieu Mulot
  5. Nathan Peiffer-Smadja
  6. Yahya Mahamat-Saleh

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  1. ScreenIT

    SciScore for 10.1101/2020.06.17.20133884: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    A search was performed via PubMed and Web of Science and Cochrane Review until 10 June 2020 with this string search: (COVID-19 OR SRAS-CoV-2
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Cochrane Review
    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:
    Limitations come from the studies which do not report adjusted effect size when mortality was not the primary endpoint. Confounding bias is high in these articles (mainly for the preprints). This meta-analysis was based on aggregated data, without access to original patient data. Most of studies are observational which do not allow to identify a causal association. This meta-analysis did not include results from the European DISCOVERY trial and the WHO SOLIDARITY trial (46). To finish, some of the included studies had very low quality of evidence (missing data, small sample size, confusion bias, bias in classification of intervention and selection bias) but the exclusion of these articles did not change the results. Few peer-reviewed studies with a comparative group analysed some other endpoints such as virological clearance, clinical improvement and arrhythmia risks. A recent randomized controlled trial with 821 asymptomatic participants in contact with a COVID-19 confirmed case, concluded hydroxychloroquine was not efficient to prevent illness in a prophylactic way (47). However, this trial had a limitation: only 16 participants had a confirmed positive RT-PCR test. A small French non-randomised trial identified a higher proportion of negative RT-PCR tests in the HCQ group (21) but two other RCT did not find any difference between the HCQ and standard care groups for clinical improvement (38,39). Several studies raised concerns about an increase of the QTc interval with HCQ...

    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 10.1016/j.cmi.2020.08.022
  3. ScreenIT

    SciScore for 10.1101/2020.06.17.20133884: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.RandomizationThe quality of each study was assessed with ROBIN-I tool following Cochrane guidelines for non-randomized studies and with Rob2 for randomized studies ( 24,25) .Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Methods and Findings: Pubmed , Web of Science , Cochrane Library , MedRxiv and grey literature were searched until 10 June 2020 .
    Pubmed
    suggested: (PubMed, SCR_004846)
          <div style="margin-bottom:8px">
        <div><b>Cochrane Library</b></div>
        <div>suggested: (Cochrane Library, <a href="https://scicrunch.org/resources/Any/search?q=SCR_013000">SCR_013000</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">A search was performed via PubMed and Web of Science and Cochrane Review until 10 June 2020 with this string search: ( COVID-19 OR SRAS-CoV2 )</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Cochrane Review</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Given that the number of articles about hydroxychloroquine and COVID-19 is rapidly growing , we also manually searched additional reference on MedRxiv preprint server and on google scholar .</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>google scholar</b></div>
        <div>suggested: (Google Scholar, <a href="https://scicrunch.org/resources/Any/search?q=SCR_008878">SCR_008878</a>)</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">RR calculation is based on Cochrane Handbook for Systematic Reviews of Interventions formula RR = number of deaths in treatment group number of participants in treatment group number of deaths in control group number of participants in control group ( 23 ) For all the other studies , reported adjusted OR , RR or HR were used.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Cochrane Handbook</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">7 articles from Medrxiv/Google Scholar were added.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Medrxiv/Google Scholar</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr></table>

    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 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 10.1101/2020.06.17.20133884v1 on medRxiv