Remdesivir for the treatment of COVID-19: a living systematic review
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Abstract
Objective Provide a timely, rigorous and continuously updated summary of the evidence on the role of remdesivir in the treatment of patients with COVID-19. Methods Eligible studies were randomized trials evaluating the effect of remdesivir versus placebo or no treatment. We conducted searches in the special L·OVE (Living OVerview of Evidence) platform for COVID-19, a system that performs regular searches in databases, trial registries, preprint servers and websites relevant to COVID-19. All the searches covered the period until 25 August 2020. No date or language restrictions were applied. Two reviewers independently evaluated potentially eligible studies according to predefined selection criteria, and extracted data on study characteristics, methods, outcomes, and risk of bias, using a predesigned, standardized form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic. Results Our search strategy yielded 574 references. Finally, we included threerandomized trials evaluating remdesivir in addition to standard care versus standard care alone. The evidence is very uncertain about the effect of remdesivir on mortality (RR 0.7, 95% CI 0.46 to 1.05; very low certainty evidence) and the need for invasive mechanical ventilation (RR 0.69, 95% CI 0.39 to 1.24; very low certainty evidence). On the other hand, remdesivir likely results in a large increase in the incidence of adverse effects in patients with COVID-19 (RR 1.29, 95% CI 0.58 to 2.84; moderate certainty evidence). Conclusions The evidence is insufficient for the outcomes critical for making decisions on the role of remdesivir in the treatment of patients with COVID-19, so it is impossible to balance potential benefits, if there are any, with the adverse effects and costs. PROSPERO Registration number: CRD42020183384.
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SciScore for 10.1101/2020.09.27.20202754: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources For any outcomes where it was not possible to calculate an effect estimate, a narrative synthesis is presented, describing the studies in terms of the direction and the size of effects, and any available measure of precision For any outcomes where data was available from more than one trial, we conducted a formal quantitative synthesis (meta-analysis) for studies clinically homogeneous using RevMan 5 [20], using the inverse variance method with the random-effects model. RevMansu…SciScore for 10.1101/2020.09.27.20202754: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
Software and Algorithms Sentences Resources For any outcomes where it was not possible to calculate an effect estimate, a narrative synthesis is presented, describing the studies in terms of the direction and the size of effects, and any available measure of precision For any outcomes where data was available from more than one trial, we conducted a formal quantitative synthesis (meta-analysis) for studies clinically homogeneous using RevMan 5 [20], using the inverse variance method with the random-effects model. RevMansuggested: (RevMan, RRID:SCR_003581)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:One of the limitations comes from the lack of precision of the result for the main outcomes. The early termination of the ACTT-1 trial can be seen as a missed opportunity in this regard [25]. In addition, all the trials concluded enrollment before the release of the RECOVERY trial which showed a mortality reduction with dexamethasone [27]. It is not clear if this factor would modify the effect, if any, of remdesivir. By now, clinicians and other decision makers are in a difficult position. The pressure to act is high, particularly after the the US Food and Drug Administration issued an emergency use authorisation of remdesivir for the treatment of COVID-19 [12]. We anticipate that the range of recommendations from different organisations should range between a suggestion against its use and a weak recommendation for its use in severe cases, especially in settings without resource constraints. There are at least 46 ongoing trials that we expect will provide data in the near future. Making sense of this information is not going to be an easy task. Systematic reviews are considered the gold standard to make sense of multiple trials addressing a similar scientific question, but the traditional model for conducting reviews has several limitations, including a high demand for time and resources [28] and a rapid obsolescence [29]. Amidst the COVID-19 crisis, researchers should make their best effort to answer the urgent needs of health decision makers yet without giving up scientifi...
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.
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