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 (1:1) to Dexamethasone therapy plus standard of care or TCZ plus standard of care. Randomization in blocks of variable size was performed in an electronic case report form system and stratified by site, age (≥ 50 years versus < 50 years), baseline PaO2/FiO2, and respiratory status (non-invasive positive-pressure ventilation, or mechanical ventilation)”
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
High |
Quote: “Patients, investigators, and health-care providers were not masked to study drug assignment”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Co-interventions of interest: Corticosteroids and Biologics were the interventions. Antivirals were not reported. Hence, not sufficient information on whether deviations arose because of the trial context. MORTALITY (D28): 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 outcome: Mortality (D28). TIME TO DEATH: Of note, 28 (38%) vs 12 (16%) participants were excluded from the time to death analysis post-randomization because they died within 3 days of enrollment. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There is likely to have been substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be high for the outcome: Time to death. |
| Missing outcome data |
Low |
Comment: 149 participants randomized; 149 participants analyzed for mortality; 109 participants analyzed for time to death.
Data available for all participants randomized for mortality. The 27% missing data from the time to death analysis were protocol violations noted and accounted for in domain 2. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unclear blinding (outcome assessor). Mortality and time to death are observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. |
| Selection of the reported results |
Some concerns |
Comment: The protocol or statistical analysis plan were not available; the trial registry was retrospective.
No information on whether the result was selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Mortality (D28). Time to death. |
| Overall risk of bias |
High |