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 (protocol): "The ratio between the treatment groups is 1:1:1, i.e., the same number of patients will be randomized to emapalumab, anakinra, or standard of care. Patients will be stratified based on glucocorticoid treatment at randomization to ensure an equal distribution between treatment arms.The randomization numbers are generated in blocks. Each block includes the three treatment groups per the ratio described above. An IWRS will be used for the randomization."
Comment: Allocation sequence random. Allocation sequence concealed |
| Deviations from intervention |
Some concerns |
Quote: "randomized, open-label, parallel group"
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No information on participant cross-over. No information on administration of co-interventions of interest: antivirals and corticosteroids. Biologics were the intervention 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 (D60 or more). Clinical improvement (D60 or more). Serious adverse events. |
| Missing outcome data |
Low |
Comment: 16 participants randomized, 16 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D60 or more). Clinical improvement (D60 or more). 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 (outcome assessor) MORTALITY Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D60 or more). CLINICAL IMPROVEMENT Clinical improvement (defined as hospital discharge but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D60 or more). SERIOUS ADVERSE EVENTS The authors reported on serious adverse events that cannot be influenced by knowledge of the intervention assignment. Risk assessed to be low for the outcomes: Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol, statistical analysis plan, registry were available (prospective registry dated March 27, 2020)
MORTALITY Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Results were probably 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 (D60 or more). CLINICAL IMPROVEMENT, SERIOUS ADVERSE EVENTS Outcomes not pre-specified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Clinical improvement (D60 or more). Serious adverse events. |
| Overall risk of bias |
Some concerns |