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 randomized in a 1:1:1 ratio to receive SOC alone (control group); SOC plus a single subcutaneous dose of 200 mg sarilumab (Sarilumab-200) or SOC plus a single subcutaneous dose of 400 mg sarilumab (Sarilumab-400). Concealed randomization was carried out by means of electronic case report forms after obtaining informed consent and stratified according to the presence of an oxygen saturation (SatO2) < 90% while breathing room air and/or a partial pressure of arterial oxygen (PaO2) < 60 mm Hg."
Comment: Allocation sequence probably random. Allocation sequence concealed. |
| 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 cross-over. No information on administration of co-interventions of interest: corticosteroids and biologics during the study. Antivirals (3 vs 7 vs 4) and anticoagulant were reported (37 vs 39 vs 39) and were balanced between groups. Hence, no sufficient information on whether deviations arose because of the trial context. MORTALITY, CLINICAL IMPROVEMENT 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 outcomes: Mortality (D28). Clinical improvement (D28). TIME TO DEATH, TIME TO CLINICAL IMPROVEMENT Participants were analyzed according to their randomized groups for the outcome. Of note, 1 vs 1 vs 0 participants were excluded from the analysis post-randomization because [1 in group (sarilumab 200) did not comply with protocol, 1 in group (sarilumab 400) they did not receive the drug. This method was considered inappropriate to estimate the effect of assignment to intervention for this 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 outcomes: Time to death. Time to clinical improvement. |
| Missing outcome data |
Low |
Comment: 118 participants randomized; 115 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Time to clinical improvement. |
| 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) CLINICAL IMPROVEMENT Clinical improvement (defined as a 2-point increase on a 263 7-category ordinal scale or hospital discharge, whichever occurred first) 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. |
| Selection of the reported results |
Low |
Comment: The protocol (dated January 5, 2022) and registry (dated April 22, 2020). 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 outcome: Mortality (D28). Time to death. Clinical improvement (D28). Time to clinical improvement. |
| Overall risk of bias |
Some concerns |