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:"Participants were randomly assigned to receive either anakinra or oSOC alone in a 1:1 ratio through a computer (SAS based) generated randomisation schedule...Randomization was performed by trained staff members using a secure, centralized, interactive web-based response system within the 20 days following the onset of COVID-19 symptoms."
Comment:Allocation sequence random Allocation sequence concealed |
| Deviations from intervention |
Some concerns |
Quote:"Open label. Study physicians, research staff, participants, and data analysts were aware of treatment allocation."
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: Biologics, antibiotics. Concerning steroids "For corticosteroids, 28 (76%) of patients in the anakinra group and 30 (88%) in the SOC group received cortico-steroids administrated at/or after inclusion." This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. 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. Of note, 2 vs 2 participants were excluded from the analysis post-randomization for unknown reasons; this will be accounted for in domain 3. Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 71 participants randomized; 71 participants analyzed for safety; 67 participants analyzed for the other outcomes.
ADVERSE AND SERIOUS ADVERSE EVENTS Data available for all participants randomized for safety. Risk assessed to be low for the outcomes: Adverse events. Serious adverse events. MORTALITY. CLINICAL IMPROVEMENT. WHO SCORE 7 AND ABOVE Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: withdrawn consent, lost to follow up Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). WHO Score 7 and above. |
| 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 (D28). CLINICAL IMPROVEMENT Clinical improvement (defined as hospital discharge) requires clinical judgement and could be affected by knowledge of intervention receipt, but it is 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) ADVERSE and SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious adverse events that may 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: Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, registry were available.
Outcome pre-specified. 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 |