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: “After signing informed consent, participants were randomly assigned in a 1:1 ratio to receive either sarilumab plus SOC (experimental group) or SOC (control group). Randomization codes were produced by means of the RERAND system integrated within the eCRF system based on Oracle, stratified by center and using blocks multiple of 2 elements. The randomization schedule was managed through the eCRF in a concealed manner.”
Comment: Allocation sequence random. Allocation probably concealed. |
| Deviations from intervention |
Low |
Quote: "Our clinical trial was a national, multicenter, randomized, open label, controlled clinical study".
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Co-interventions of interest were reported during trial: corticosteroids in 77 vs 84 participants; tocilizumab in 18 vs 16 participants and remdesivir in 3 vs 2 participants. Hence, deviations did not arise because of the trial context. Our analysis is an 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). Time to death. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Time to WHO score 7 and above. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 201 participants randomized; 201 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Time to WHO score 7 and above. 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. TIME TO DEATH Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. (TIME TO) WHO SCORE 7 AND ABOVE For this outcome, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: WHO score 7 and above (D28). Time to WHO score 7 and above. (TIME TO) CLINICAL IMPROVEMENT Clinical improvement (defined as hospital discharge) requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). Time to clinical improvement. ADVERSE AND SERIOUS ADVERSE EVENTS. The authors reported on adverse events that contain both clinically- and laboratory-detected events, which 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: Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol (dated May 5th, 2020), statistical analysis plan, registry (dated May 26th 2020) were available.
Outcome pre-specified (in the protocol with appropriate timepoint) 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. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Time to WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |