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 who were eligible for randomisation to tocilizumab were assigned to either usual standard of care or usual standard of care plus tocilizumab in a 1:1 ratio using web-based simple (unstratified) randomisation with allocation concealed until after randomisation.”
Comment: Allocation sequence random. Allocation sequence concealed. No baseline imbalance. |
| Deviations from intervention |
Low |
Quote: "Open-label study"
Comment: Unblinded study(participants and personnel/carers). Deviations from the intended intervention that arose because of the trial context: Administration of co-interventions of interest, antivirals, biologics and corticosteroids, reported and balanced between groups. 1647 allocated to tocilizumab received tocilizumab but this probably did not arise because of the trial context. 77 of those allocated to usual care received tocilizumab. Overall, the deviation was too small to affect the outcome. Data were analyzed using intention-to-treat analysis. No patients were excluded from the analysis post-randomization. This method was considered appropriate to estimate the effect of assignment to intervention was considered appropriate. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). |
| Missing outcome data |
Low |
Comment: 4116 patients randomized; 4116 patients analyzed. 1964/2022 (97%) patients of those allocated to tocilizumab and 2049/2094 (98%) of those allocated to usual care had a completed follow−up form at time of analysis. Data not available for all or nearly all participants. No evidence that the result is not biased. Reason for missing data: lack of completed follow-up form Missingness due to documented reason unrelated to the outcome. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). |
| 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 Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as discharge from hospital) requires clinical judgement and could be affected by knowledge of intervention receipt, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, registry were available.
Mortality outcome was pre-specified. The authors specified "duration of hospital stay" and despite a slight difference we consider it consistent with discharge alive from hospital (taken as clinical improvement). Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified (interim analysis for adult population) Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement(D28). |
| Overall risk of bias |
Some concerns |