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 with equal probability to all open arms available at the site using a centrally-managed computer-generated random sequence"
Comment: Allocation sequence random. Allocation sequence 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. Co-interventions of interest: corticosteroids and biologics were reported and were balanced between groups. Antivirals were reported but not balanced between groups: 67.9% vs 53.3% vs 67.3% for namilumab, infliximab and usual care respectively. 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. Data for the outcomes were analyzed using 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). Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 146 participants randomized; 138 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 2, 6 and 0 participants were missing from the namilumab, infliximab and usual care arms respectively due to withdrawals. 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). 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 (outcome assessor). MORTALITY: Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: 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 outcome: Clinical improvement (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 (posted online 12 February 2021) and prospective registry (registered online 14 May 2020) were available.
Outcomes were 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). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |