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: “Patients were randomly assigned through a random sequence generator (derived from http://www.randomization.com) to tocilizumab or baricitinib on 1:1 ratio.”
From contact with authors:"Author APK (working on a separate Department) was responsible for the randomization and informed clinicians which compound was to be applied after the application for enrolment of a new patient. Following randomization, the treatment applied was not blinded." Comment: Allocation sequence random. Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Open-label”.
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 was probably balanced between groups: antivirals, corticosteroids and biologics, based on the detailed description of standard of care given to all participants. Hence, deviations probably did not arise because of the trial context. MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, ADVERSE EVENTS, SERIOUS ADVERSE EVENTS Our analysis for the binary outcomes is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. No participants were missing in time-to-event analyses. Risk assessed to be low 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. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Time to death. Time to clinical improvement. Time to WHO score 7 and above. |
| Missing outcome data |
Low |
Comment: 251 participants randomized; 251 participants analyzed.
Data available for all or nearly all participants randomized. 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 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). Time to WHO score 7 and above. (TIME TO) 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). Clinical improvement (D60 or more). Time to clinical improvement. br/> 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 |
Low |
Comment: The prospective registry was available (dated October 19th, 2021)
MORTALITY (D28). TIME TO DEATH. CLINICAL IMPROVEMENT (D28). TIME TO CLINICAL IMPROVEMENT. WHO SCORE 7 AND ABOVE. TIME TO 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). Time to death. Clinical improvement (D28). Time to clinical improvement. WHO score 7 and above (D28). Time to WHO score 7 and above. MORTALITY (D60 OR MORE). CLINICAL IMPROVEMENT (D60 OR MORE). ADVERSE EVENTS. SERIOUS ADVERSE EVENTS Outcome data acquired from direct contact with authors. Analysis performed by the COVID-NMA. Risk assessed to be low for the outcome: Mortality (D60 or more). Clinical improvement (D60 or more). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |