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 |
Some concerns |
Quote: "Eligible patients (one or two days after hospitalization) were randomly distributed to the control and intervention groups by block randomization (1:1 ratio."
Comment: Allocation sequence probably random. Unclear allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote: "In this study, patients, investigators, and outcome assessors did not inform which group received an intervention. Besides, a placebo was not used in the control group."
Comment: Unclear blinding (unclear if participants and personnel/carers blinded) Deviations from intended intervention arising because of the study context: No participant cross-over. Biologics were the intervention. Corticosteroids reported and balanced between groups. Antivirals reported and not balanced between groups: 35% in the Tocilizumab versus 10% in the standard care arm. This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. MORTALITY, CLINICAL IMPROVEMENT, SAE Data for the outcome were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). Serious adverse events. TIME TO DEATH Participants were analyzed according to their randomized groups for the outcome. Of note, 3 vs 1 participants were excluded from the analysis post-randomization 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 some concerns for the outcome: Time to death. |
| Missing outcome data |
Some concerns |
Comment: 40 participants randomized; 36 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. 3 participants in the treatment arm and 1 in the standard care arm refused to participate before start of the intervention. 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). Time to death. Clinical improvement (D28). 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). Time to death. Clinical improvement (D28). Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The trial registry was available.
MORTALITY Outcome has different timepoint listed in the registry. 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: Mortality (D28). Time to death. CLINICAL IMPROVEMENT, SAE Outcomes 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). Serious averse events. |
| Overall risk of bias |
High |