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: “An independent unblinded statistician used a computer-generated randomisation list with a permuted block size of 6 to assign participants to treatment groups and was not involved in the rest of the trial. He was the only person who knew the size of the blocks. All treatment assignments were stored in a secure area on a server with restricted access. The randomisation list was integrated by the study data manager in the electronic case-report form (eCRF).”
Comment: Allocation sequence random. Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: “All participants, care providers and other study personnel were masked to treatment assignment. The baricitinib drug and matching placebo were provided by Eli Lilly and Company.”
Comment: Blinded study (participants and personnel/carers) MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, and 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 low for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D60 or more). WHO score 7 and above (D28). Serious adverse events. TIME TO CLINICAL IMPROVEMENT Participants were analyzed according to their randomized groups for the outcome. Of note, 3 vs 6 participants were excluded from the analysis post-randomization because they did not receive the intervention. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcome: Time to clinical improvement. |
| Missing outcome data |
Low |
Comment: 284 participants randomized; 275 participants analyzed; 19 (7%) missing data.
MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, SERIOUS ADVERSE EVENTS Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 3 vs 6 were excluded from the analysis post-randomisation because they did not receive the intervention: 3 vs 3 withdrew consent, 1 investigator decision, and 2 did not meet inclusion criteria. Also, 3 vs 1 withdrew consent, 3 vs 2 was investigator decision, and 1 vs 0 was lost to follow up. Missingness could not depend on the true value of the outcome as the main reasons are due to outside factors. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D60 or more). WHO score 7 and above (D28). Serious adverse events. TIME TO CLINICAL IMPROVEMENT Data available for nearly all participants randomized. Of note, 9 of the 19 missing participants were addressed in domain 2; 3 vs 1 withdrew consent, 3 vs 2 was investigator decision, and 1 vs 0 was lost to follow up. Risk assessed to be low for the outcome: Time to clinical improvement. |
| 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 (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective trial registry was available (dated May 18, 2021).
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). Mortality (D60 or more). Clinical improvement (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). Serious adverse events. |
| Overall risk of bias |
Some concerns |