| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: “Patients who were eligible for randomisation to tocilizumab were assigned to either usual 136 standard of care or usual standard of care plus tocilizumab in a 1:1 ratio using web-based 137 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. 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. 1333/1602 (83%) allocated to tocilizumab received tocilizumab but this probably did not arise because of the trial context. 44/1664 (3%) 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 |
Quote: "For this preliminary report, information on the primary outcome is available for 92% of randomised patients. Those patients who had not been followed for 28 days and were not known to have died by the time of the data cut for this preliminary analysis (8 February 2021) were either censored on 8 February 2021 or, if they had already been discharged alive, were right- censored for mortality at day 29."
Quote: "For this preliminary report, information on the primary outcome is available for 92% of patients." Comment: 4116 patients randomized; 4116 patients analyzed. Data for the primary outcome (all-cause mortality at day 28) was available for 92% of participants. 1602/2022 (79%) patients of those allocated to tocilizumab and 1664/2094 (79%) 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: interim analysis; 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. Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). 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 assessment (D28). |
| Overall risk of bias |
Some concerns |