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: "Block
randomisation, with a block size of 3, was used to decrease
the risk of imbalance. Randomisation was stratified by
geographical region (North America, western Europe,
eastern Europe, Latin America, and other). Randomisation
was done by interactive response technology. The
investigator contacted the interactive response technology
system, which assigned a randomisation number to each
participant, linking them to their unique medication
number. Medication numbers were automatically
assigned to medication packs. Study treatments were identical in packaging, appearance, taste, and odour."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "Participants, investigator staff, persons performing the assessments, and CTT will remain blind to the identity of the treatment from the time of randomization until database lock"
Comment: Blinded study (participants and personnel/carers) MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, AE, SAE 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). Adverse events. Serious adverse events. TIME TO CLINICAL IMPROVEMENT Participants were not analyzed according to their randomized groups for the outcome. Of note, 1 participant in the ruxolitinib arm was excluded due to missing data which is accounted for in domain 3. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be low for the outcome: Time to clinical improvement. |
| Missing outcome data |
Some concerns |
Comment: 432 participants randomized; 431-432 participants analyzed for efficacy; 424 participants analyzed for safety.
Data not available for nearly all participants randomized. No evidence that the result is not biased. Reasons: 18 vs 6 discontinued study treatment due to diverse reasons. 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). Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (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). Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and registry (dated April 24, 2020) were available.
Efficacy outcomes pre-specified. Safety outcome (SAEs) not pre-specified in the registry, but specified in the protocol. 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). Time to clinical improvement. WHO score 7 and above (D28). Time to WHO score 7 and above. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |