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 |
Some concerns |
Quote: "patients were randomized in a 2:2:1 ratio to IV sarilumab 400 mg, sarilumab 200 mg, or placebo"
Comment: Allocation sequence probably random. No information on allocation concealment. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "An unmasked pharmacist was responsible for preparation of all study interventions. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the study"
Comment: Blinded study (participants and personnel/carers). Data 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). Mortality (D60 or more). Clinical improvement (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 1407 participants randomized; 1330 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons for missing data: randomized but not treated (n=42), Investigator/sponsor decision (n=12), withdrawal of consent (n=12), death before start of treatment (n=8), other (n=2), unknown (n=65). Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). 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). Clinical improvement (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The trial registry was available and consulted (up to version dated March 26th, 2020).
MORTALITY, SERIOUS ADVERSE EVENTS 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). Mortality (D60 or more). Serious adverse events. CLINICAL IMPROVEMENT, ADVERSE EVENTS Outcome not pre-specified No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Clinical improvement (D28). Adverse events. |
| Overall risk of bias |
Some concerns |