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: “Randomization was performed with random permuted blocks in a 2:1 ratio using a block size of six and programmed by a biostatistician with SAS, version 9.4, for Windows. The randomization file was imported to REDCap, and the investigator randomized patients in REDCap after confirming their eligibility for inclusion.”
Comment: Allocation sequence random Allocation sequence probably concealed |
| Deviations from intervention |
Some concerns |
Quote: “open-label”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of co-interventions of interest: corticosteroids. Antivirals were not administered. Hence, no information on whether deviations arose because of the trial context. Our analysis for the binary outcome is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Serious adverse events. MORTALITY D60, TIME TO DEATH RoB assessment consulted from The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group "Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis." JAMA. 2021;326(6):499–518 due to unavailability of trial details. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. |
| Missing outcome data |
Low |
Comment: 88 participants randomized; 86 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Serious adverse events. MORTALITY D60, TIME TO DEATH RoB assessment consulted from The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group "Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis." JAMA. 2021;326(6):499–518 due to unavailability of trial details. Risk assessed to be low for the outcomes: Mortality (D60 or more). Time to death. |
| 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 D28 Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as hospital discharge) requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). WHO SCORE 7 AND ABOVE For this outcome, 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). SERIOUS ADVERSE EVENTS The authors reported on serious adverse events that contain both clinically- and laboratory-detected events, which 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: Serious adverse events. MORTALITY D60, TIME TO DEATH: RoB assessment consulted from The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group "Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis." JAMA. 2021;326(6):499–518 due to unavailability of trial details. Risk assessed to be low for the outcomes: Mortality (D60 or more). Time to death. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were not available and the registry was retrospective (dated October 8, 2021).
No information on whether the result was selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Serious adverse events. MORTALITY D60, TIME TO DEATH: RoB assessment consulted from The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group "Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis." JAMA. 2021;326(6):499–518 due to unavailability of trial details. Risk assessed to be low for the outcome: Mortality (D60 or more). Time to death. |
| Overall risk of bias |
Some concerns |