Efficacy of remdesivir in COVID-19 patients with a simulated two-arm controlled study

  1. Chen-Yang Hsu
  2. Chao-Chih Lai
  3. Amy Ming-Fang Yen
  4. Sam Li-Sheng Chen
  5. Hsiu-Hsi Chen

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Abstract

While the recent study on the compassionate use of remdesivir for COVID-19 patients has shown a 68% clinical improvement 7 it is a one-arm study that renders the evaluation of the efficacy in reducing death and the length of stay of hospitalization intractable due to a lacking of the control group. We came up with a two-arm controlled study design to simulate the treated and the untreated (control group) group by applying two respective transition models to the empirical data on dynamics of the disease severity (Figure 2 of the original article 7 ) that are classified into low- (no and low oxygen supplement), medium- (non-invasive ventilator and high oxygen supplement), and high-(ECMO and invasive ventilator) from enrolment until discharge, death or the end of follow-up. By using a simulated two-arm controlled study, the remdesivir treatment group as opposed to the control group led to a statistically significantly 29% (95% CI: 22-35%) reduction of death from COVID-19. The treated group also revealed a 33% (95% CI 28-38%) significantly higher odds of discharge than the control group. The median time to discharge for the treated group (5.5 days, 16.5 days, and 29.5 days for low-, medium-, and high-risk state, respectively) was around half of those of the control arm. Our results with a simulated two-arm controlled study have not only corroborated the efficacy of remdesivir but also made great contribution to designing a further large-scale randomized controlled trial. They have significant implications for reducing transmission probability and infectious time of COVID-19 patients when contacting with susceptible health care workers during hospitalization.

Key Points

Question

What is the efficacy of remdesivir in reducing advanced disease state or death from COVID-19 and the length of stay of hospitalization?

Findings

Remdesivir treatment results in a 33% significantly higher odds of discharge, a 29% significantly lower risk of death, and a 39% significantly lower risk for the combined endpoint of severe status and death. The median time to discharge for the remdesivir treated group was around half of the median time-to-discharge compared with the control arm.

Meaning

Remdesivir is effective in treating COVID-19 patients in terms of enhancing recovery and accelerating discharge.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.05.02.20088559: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationSuch a two-arm controlled study, which is equivalent to a randomized controlled trial, was therefore simulated and used for evaluating the efficacy of remdesivir treatment in accelerating discharge and decelerating subsequent deaths.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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: 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 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 10.1101/2020.05.02.20088559 on medRxiv