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: “Per pre-specified plans for a play-the-winner design, the first 30 patients were randomized 1:1 to sarilumab or no additional treatment beyond the current SOC. The randomization ratio was then adapted after assessment of the primary outcome in the first 30 patients and again after each additional 15-patient block. Following a pre-specified scheme, the study statistician determined the change in randomization ratio based on the observed results. The randomization list was sent to the VA Information Technology Department and then embedded within the VA electronic health record system. Neither the allocation ratio nor randomization list was shared with the study team.”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: “Open-label. Investigators were blinded to the individual patient outcomes, aggregate outcomes, and the randomization ratio after adaptation.”
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: biologics, antivirals and corticosteroids reported and generally balanced between groups. Hence, deviations did not arise because of the trial context. 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 low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). |
| Missing outcome data |
Low |
Comment: 50 participants randomized; 50 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). |
| 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 Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). WHO SCORE 7 AND ABOVE For WHO score 7 and above, 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). CLINICAL IMPROVEMENT Clinical improvement (defined as 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). |
| Selection of the reported results |
Some concerns |
Comment: The protocol, statistical analysis plan, registry (submitted April 20, 2020) were available.
MORTALITY. WHO SCORE 7 AND ABOVE. 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 outcomes: Mortality (D28). WHO score 7 and above (D28). CLINICAL IMPROVEMENT 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). |
| Overall risk of bias |
Some concerns |