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: "Eligible patients were randomly assigned (2:2:1)
to one dose of intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo according to a central randomisation scheme using permuted blocks of five and implemented through an interactive response technology (IRT). Randomisation was stratified by severity of illness (severe or critical) and use of systemic corticosteroids (yes or no). Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. An unmasked pharmacist was responsible for the preparation and dispensation of all study interventions."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study."
Comment: Blinded study (participants, personnel/carers) Data for the binary outcomes were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Participants were analyzed according to their randomized groups for the time-to-event outcome. Of note, 2 vs 2 patients were excluded from the analysis because they did not start the treatment. Nevertheless, we consider the analysis appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to clinical improvement. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 420 participants randomized; 416 participants analyzed.
Data available for all or nearly all participants. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to clinical improvement. Adverse events. 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. Blinded study (outcome assessor) Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to clinical improvement. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The study registry was available.
Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified for these outcomes. Risk assessed to be low for the outcomes: Mortality (D28). Time to clinical improvement. Adverse events. Serious adverse events. Mortality outcome was not pre-specified for day 60 in the registry. No information whether the result was selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for the outcome: Mortality (D60 or more). |
| Overall risk of bias |
Some concerns |