Note: The risk of bias by domain corresponds to the highest risk of bias among outcomes by domain.
The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.
| Bias | Author's judgement | Support for judgement |
| Randomization |
Some concerns |
Quote from the protocol: "Participants who meet eligibility criteria are randomized in a 1:1 ratio to 1 of 2 treatment groups on Day 1 using an IWRS and assigned a subject number." Comment: Allocation sequence random. Allocation sequence concealed. the 10-day remdesivir group had a greater proportion of male participants and participants at higher severity. |
| Deviations from intervention |
Some concerns |
Quote: "open-label" Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant crossover. No information on co-interventions of interest: glucocorticoids, antivirals and biologics. Hence, no information on whether deviations arose because of the trial context. MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, AE, SAE Data for the outcome were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. TIME TO CLINICAL IMPROVEMENT Participants were analyzed according to their randomized groups for the outcome. Of note, 3 vs 2 participants were excluded from the analysis post-randomization because they did not receive the drug. This method was considered inappropriate to estimate the effect of assignment to intervention for this time-to-event outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcome: Time to clinical improvement. |
| Missing outcome data |
Low |
Comment: 402 participants randomized; 397 participants analyzed. Data available for all or nearly all participants. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY, WHO SCORE 7 AND ABOVE Mortality is an observer-reported outcome not involving judgement. For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcome: Mortality (D28). WHO score 7 and above (D28). (TIME TO) CLINICAL IMPROVEMENT, AE, SAE Clinical improvement requires clinical judgement and could be affected by knowledge of intervention receipt. Also, the authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events. All these outcomes can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). Time to clinical improvement. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan were available. Outcomes reported as pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality (D28). WHO score 7 and above (D28). Clinical improvement (D28). Time to clinical improvement. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |