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 and consenting patients were assigned in a 1:1 ratio to either usual standard of care plus baricitinib or usual standard of care alone, using web-based simple (unstratified) randomisation with allocation concealed until after randomization.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Open-label. Participants and local study staff were not masked to the allocated treatment. The Trial Steering Committee, investigators, and all other individuals involved in the trial were masked to outcome data during the trial.”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: 11/3950 (0.3%) of particpants with completed follow-up randomised to control group did receive the study drug. Overall, the deviation was too small to affect the outcome. Administration of co-interventions of interest - biologics, antivirals and corticosteroids - was reported and balanced between groups (webtable 2): steroids: 89% vs 90%; antivirals: 21% vs 21%; tocilizumab or sarilumab: 26% vs 29%). 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). |
| Missing outcome data |
Low |
Comment: 8156 participants randomized; 8034 participants with complete follow up analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (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). CLINICAL IMPROVEMENT Clinical improvement (defined as discharged alive) 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 |
Low |
Comment: The protocol, statistical analysis plan and prospective registry (dated May 11, 2020) were available.
Mortality outcome pre-specified in the registry and protocol; clinical improvement outcome pre-specified in the protocol and statistical analysis plan. 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). Clinical improvement (D28). |
| Overall risk of bias |
Some concerns |