Evaluation of the effectiveness of remdesivir in severe COVID-19 using observational data from a prospective national cohort study

  1. B N Arch
  2. D Kovacs
  3. J T Scott
  4. A P Jones
  5. E M Harrison
  6. A Rosala-Hallas
  7. C G Gamble
  8. P J M Openshaw
  9. J K Baillie
  10. M G Semple

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Abstract

Background

Remdesivir has been evaluated in clinical trial populations, but there is a sparsity of evidence evaluating effectiveness in general populations.

Methods

Adults eligible to be treated with remdesivir, requiring oxygen but not ventilated, were identified from UK patients hospitalised with COVID-19. Patients treated with remdesivir within 24h of hospitalisation were compared with propensity-score matched controls; estimates of effectiveness were calculated for short-term outcomes (14-day mortality, 28-day mortality, time-to-recovery among others) using multivariable modelling.

Results

9,278 out of 39,330 patients satisfied eligibility criteria. 1,549 patients were identified as ‘treated’ and matched with 4,964 controls. Patients were 62% male, mean (SD) age 63.1 (15.6) years, 80% ‘White’ ethnicity, and symptomatic for a median of 6 days prior to baseline. There was no statistically significant benefit of remdesivir at 14 days in terms of mortality or clinical status; there were signals of effectiveness in time-to-recovery after day 9, and a reduction in 28-day mortality.

Conclusion

In a real-world setting, initiation of remdesivir within 24h of hospitalisation in conjunction with standard of care was not associated with a benefit at 14 days but supports clinical trial evidence of a potential reduction in 28-day mortality.

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  1. Version published to 10.1101/2021.06.18.21259072v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.06.18.21259072: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: 19,20 Study materials including protocol, revision history, case report forms (CRFs), study information and consent forms, are available online20 Ethical approval for data collection was given by the South Central - Oxford C Research Ethics Committee in England (Ref: 13/SC/0149) and by the Scotland A Research Ethics Committee (Ref: 20/SS/0028).
    Consent: Under the Control of Patient Information (COPI) notice 2020 for urgent public health research, processing of demographic and routine clinical data from medical records for research does not require consent in England and Wales. In Scotland, a waiver for consent was obtained from the Public Benefit and Privacy Panel.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisThe sample size was limited by the number of patients treated with remdesivir in practice and while a formal sample size calculation was not undertaken a sample size of more than 500 patients treated with remdesivir was considered sufficient for a meaningful analysis.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Propensity score matching was carried out using the package MatchIt in R v3.6.1; all other analyses were carried out using SAS v9.4.
    SAS
    suggested: (SASqPCR, RRID:SCR_003056)

    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 limitations in that effectiveness estimates are not from randomised patients, and the data collected reflect local practice by the clinical teams at numerous hospital sites. The study was designed pragmatically to be simple enough to be rapidly implemented, using data that were being collected under a generic protocol. The analysis was planned and made open for comment prior to any data being provided for analysis. Data completeness for baseline characteristics and final clinical outcomes were found to be extremely good thanks to the diligence of participating sites throughout the country. Daily follow-up data was less available than expected, and this meant that two outcomes and clinical status at day 15 could not be derived as planned. Inclusion and exclusion criteria were used to define a cohort that represented the type of patient that would have been eligible to have received remdesivir, and with the greatest potential to benefit from it, according to the existing evidence base. This created a clear analysis cohort with similar baseline level of severity of COVID-19. 73% of patients given remdesivir were excluded – chiefly because their treatment did not start within 24 hours of baseline. We justify their exclusion as the data collection tool could not guarantee determination of clinical status at start of treatment at other times. Other remdesivir patients were excluded because they required respiratory support or ECMO at baseline. These excluded patients are ...

    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.
    • Thank you for including a protocol registration statement.

    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.

  3. Version published to 10.1101/2021.06.18.21259072v1 on medRxiv