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 randomly assigned in a 1:1 ratio to receive usual care plus sarilumab (sarilumab group) or usual care alone (usual care group) via a web-based secure centralised system. An independent statistician provided a computer-generated randomisation list stratified by centre and blocked with random block size (randomly selected among 2 and 4); the block size was unknown to the investigators and statisticians analysing the data."
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: “open-label study”
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 were reported in Table S2: anticoagulants (41 vs 45), hydroxychloroquine (2 vs 8), antibiotics (42 vs 43), antivirals (2 vs 3), immuno-modulators (0 vs 3) and corticosteroids (9 vs 17). This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concerns as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. MORTALITY. CLINICAL IMPROVEMENT. WHO SCORE 7 AND ABOVE. ADVERSE EVENTS. SERIOUS ADVERSE EVENTS. 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). Mortality (D60 or more). Clinical improvement (D28). Clinical improvement (D60 or more). WHO score 7 and above (D28). Adverse events. Serious adverse events. TIME TO DEATH. TIME TO CLINICAL IMPROVEMENT. TIME TO WHO SCORE 7 AND ABOVE Participants were analyzed according to their randomized groups for the outcome. Of note, 0 vs 4 participants were excluded from the analysis post-randomization because they withdrew consent which will be taken into account in ROB 3. Risk assessed to be some concerns for the outcomes: Time to death. Time to clinical improvement. Time to WHO score 7 and above |
| Missing outcome data |
Low |
Comment: 148 participants randomized; 144 participants analyzed.
Data available for all or nearly all participants randomized. Of note, 0 vs 4 participants withdrew consent and asked for their personal data to be erased. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). 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). Mortality (D60 or more). 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 outcome: WHO score 7 and above (D28). Time to WHO score 7 and above. CLINICAL IMPROVEMENT. 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). Clinical improvement (D60 ore more). Time to clinical improvement. ADVERSE and SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious adverse events that may 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 |
Some concerns |
Comment: The prospective registry (March 27th, 2020) and prospective protocol (March 24, 2020) were available.
MORTALITY. TIME TO DEATH. TIME TO CLINICAL IMPROVEMENT. WHO SCORE 7 AND ABOVE. ADVERSE AND SERIOUS ADVERSE EVENTS. 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). Mortality (D60 or more). Time to death. Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. CLINICAL IMPROVEMENT. TIME TO WHO SCORE 7 AND ABOVE. Outcomes not pre-specified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Clinical improvement (D28). Clinical improvement (D60 or more). Time to WHO score 7 and above. |
| Overall risk of bias |
Some concerns |