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: "Participants were randomized via a centralized
computer program to each intervention (available locally) starting with balanced assignment"
Comment: Allocation sequence random. Allocation sequence concealed. Baseline imbalances appear compatible with chance. |
| Deviations from intervention |
Low |
Quote: "open-label design"
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Administration of co-interventions of interest (antivirals, corticosteroids and biologics) were balanced between arms. Hence, deviations did not arise because of the trial context. MORTALITY, SERIOUS ADVERSE EVENTS 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 low for the outcomes: Mortality (D28). Serious adverse events. TIME TO DEATH Participants were analyzed according to their randomized groups for the outcome. Of note, 6 vs 7 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. Risk assessed to be low for the outcome: Time to death. |
| Missing outcome data |
Low |
Comment: 2000 participants randomized; 1979 participants analyzed for mortality, 1980 participants analyzed for serious adverse events, 1987 participants analyzed for time to death.
Data available for all or nearly all participants randomized. Of note, 6 vs 7 withdrew consent and 3 vs 5 had no outcome available. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Serious adverse events. |
| Measurement of the outcome |
Low |
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 Mortality is an 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 only laboratory-detected events, which cannot be influenced by knowledge of the intervention assignment. Risk assessed to be low for the outcome: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocols (prospective core protocol dated July 10th, 2019 and retrospective pandemic appendix to core protocol dated May 18th, 2020), statistical analysis plan (retrospective: dated February 23rd, 2021), and prospective registry (dated April 13th, 2016 up to version March 25, 2020) were available.
Outcomes 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). Time to death. Serious adverse events. |
| Overall risk of bias |
Low |