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 in a 1:1 ratio to receive standard of care with or without a single
dose of tocilizumab ... via a web-based secure centralized system. A computer-generated assignment
randomization list stratified by ICU eligibility and use of hydroxychloroquine and blocked
with varying block sizes unknown to the investigators.”
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. Antivirals and corticosteroids were reported and balanced between groups. Biologics versus standard care was the comparison. Hence, deviations did not arise because of the trial context. Our analysis for the 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). Time to death. WHO score 7 and above (D28). Time to WHO score 7 and above. |
| Missing outcome data |
Low |
Comment: 354 participants randomized; 354 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. WHO score 7 and above (D28). Time to WHO score 7 and above. |
| Measurement of the outcome |
Low |
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 Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). 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. |
| Selection of the reported results |
Low |
Comment: The prospective trial registry was available (dated April 3rd, 2020).
MORTALITY. TIME TO DEATH. Outcome 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 outcome: Mortality (D28). Time to death. (TIME TO) WHO SCORE 7 AND ABOVE Outcome not pre-specified, but was a post-hoc analysis performed to facilitate comparison with other trials of tocilizumab in similar populations. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified or post-hoc with reasonable justification. Risk assessed to be low for the outcome: WHO score 7 and above (D28). Time to WHO score 7 and above. |
| Overall risk of bias |
Low |