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: "All eligible subjects will be centrally randomized using an interactive response technology (IRT) that will assign the subjects to either acalabrutinib plus BSC versus BSC, stratified by the stratification factors" (protocol)
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 information on participant cross-over. No information on administration of co-interventions of interest: antivirals, corticosteroids and biologics Hence, no information on whether deviations arose because of the trial context. MORTALITY. ADVERSE AND SERIOUS ADVERSE EVENTS 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). Adverse events. Serious adverse events. TIME TO CLINICAL IMPROVEMENT Participants were analyzed according to their randomized groups for the outcome. Of note, 0 vs 2 participants were excluded from the analysis post-randomization because they did not have one post-baseline result to be included which is missing data and accounted for in domain 3. This method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be some concerns for the outcomes: Time to clinical improvement. |
Missing outcome data |
Low |
Comment: 62 participants randomized; 62 participants analyzed for the safety outcomes; 60 analyzed for the time to clinical improvement.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Time to clinical improvement. 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 Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). TIME TO CLINICAL IMPROVEMENT Clinical improvement (defined as [Time From Randomization to Clinical Improvement of at Least 2 Points on a 9-point Category Ordinal Scale]) 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: Time to clinical improvement. ADVERSE EVENTS The authors reported on 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: Adverse events. SERIOUS ADVERSE EVENTS The authors reported on serious adverse events that contain only laboratory-detected events, which 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 (consulted up to version dated July 6, 2020)
MORTALITY. ADVERSE AND SERIOUS ADVERSE EVENTS Outcomes 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 outcome: Mortality (D28). Adverse events. Serious adverse events. TIME TO CLINICAL IMPROVEMENT Outcome not pre-specified in the registry. 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: Time to clinical improvement. |
Overall risk of bias |
Some concerns |