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 randomised in a 1:1 ratio to receive
either standard care or tocilizumab plus standard
care, with random blocks of sizes 2, 4, 6, and 8, and
stratified by age (<60 and ≥60 years) and sex, according
to a computer generated schedule using the sample
function of software R 3.6.3 (R Foundation). Allocation
concealment was ensured by a central automated web
accessed system (REDCap), developed by CZO.”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: “open label” trial.
Comment: Unblinded study. Deviations from intended intervention arising because of the study context: Cross over: 2/64 (3%) of the control arm received tocilizumab. Co-interventions of interest, corticosteroids and antivirals, were reported, but no information on another co-intervention of interest: biologics. Hence, this domain was rated as some concern as not enough information on deviations that arose because of the trial context were reported. Data for the outcome were analyzed using intention-to-treat analysis for this outcome. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be some concerns for the outcome: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 129 patients randomized; 129 patients analyzed.
Data available for all or nearly all participants. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| 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. 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: Mortality (D28). WHO score 7 and above (D28). Clinical improvement(defined as discharged alive) requires clinical judgement and could be affected by knowledge of intervention receipt. Also, the authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected outcomes. All these outcomes can be influenced by knowledge of the intervention assignment. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The published protocol, statistical analysis plan and registry were available.
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 outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |