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 |
Low |
Quote: "Patients were then randomly assigned to one of the four arms using a Web-based
randomization system (UNcovApp ®) that allows maintaining concealment until the closest
time to the start of treatment in one of the 4 arms."
Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: "open parallel-group multi-centre randomised controlled trial"
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of all co-interventions of interest, such as biologics. Only study antivirals were administered as per group assignment. Corticosteroids were reported and balanced between groups. Hence, no information on whether deviations arose because of the trial context. MORTALITY, SERIOUS ADVERSE EVENTS Our analysis for the binary outcome is an 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 outcome: Mortality (D28). Serious Adverse Events. TIME TO DEATH Of note, 3 vs 8 vs 4 vs 1 participants were excluded from the analysis post-randomization due to missing data which is accounted for in domain 3. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be some concerns for the outcome: Time to death. |
| Missing outcome data |
Low |
Comment: 649 participants randomized; 633 participants analyzed.
Data available for nearly all participants randomized. Risk assessed to be low for the outcome: Mortality (D28). Time to death. 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. TIME TO DEATH Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. SERIOUS ADVERSE EVENTS The authors reported on serious adverse events that contain clinically-detected events (severe diarrhea and drug-related exanthema), which can be influenced by knowledge of the intervention assignment (severe diarrhea), but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry (dated April 22nd, 2020) was available.
Outcome 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 outcome: Mortality (D28). Time to death. Serious adverse events. |
| Overall risk of bias |
Some concerns |