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|
|Quote: "Eligible patients were randomly assigned using block randomisation in a 1:1 ratio to receive open-label tocilizumab plus current standard care (tocilizumab group) or current standard care alone (standard care group). The randomisation sequence was generated using SAS, version 9.4 and an interactive web response system. Randomisation numbers were assigned in sequential order to the study sites according to the pregenerated sequence provided by the investigational medicinal product team at the Medanta Institute of Education and Research."
Comment: Allocation sequence random.
Allocation sequence concealed.
|Deviations from intervention||
|Quote: "After randomisation, none of the study personnel or patients was masked to treatment assignment in this open-label trial."
Comment: Unblinded study (participants and personnel/carers).
Deviations from intended intervention arising because of the study context.
One patient randomly assigned to the standard care group inadvertently received tocilizumab at baseline and was included in the tocilizumab group for all analyses (one cross-over)
Information on the administration of co-interventions of interest was provided: antivirals and corticosteroids. Biologics were not reported.
Hence, this domain was rated as some concern as not enough information on deviations that arose because of the trial context were reported.
Participants were not analyzed according to their randomized groups for the outcome.
Of note, 1 participant randomized to the control group was analyzed in the intervention group. Nevertheless, we considered the analysis to be probably appropriate to estimate the effect of assignment to intervention.
Risk assessed to be some concerns for the outcomes: Mortality (D28). Adverse events. Serious adverse events.
|Missing outcome data||
|Comment: 180 participants randomized; 180 participants analyzed for mortality, adverse events and serious adverse events.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. Serious adverse events.
|Measurement of the outcome||
|Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Unblinded study (outcome assessor)
Mortality is an observer-reported outcome not involving judgement.
Risk assessed to be low for the outcome: Mortality (D28).
Also, the authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events. All these outcomes can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic.
Risk assessed to be some concerns for the outcomes: Adverse events. Serious adverse events.
|Selection of the reported results||
|Comment: The protocol, statistical analysis plan, 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 outcome: Mortality (D28). Adverse events. Serious adverse events.
|Overall risk of bias||