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: “Eligible patients were randomized in a 1:1 ratio to KB109 plus SSC or SSC alone groups via an interactive response technology system.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
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: 5 participants in the intervention group crossed over into the control group. In the outpatient setting, we consider no important cointerventions of interest. 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: Adverse events. Serious adverse events. |
Missing outcome data |
Some concerns |
Comment: 350 participants randomized; 350 participants analyzed for safety outcomes.
Data probably not available for all or nearly all participants. No evidence that the result is not biased. Reasons for missing data: discontinued intake of study product (9 vs 7) [adverse event (4 vs 1), lost to follow-up (1 vs 0), withdrew consent (0 vs 3), withdrawal by patient (3 vs 0), hospitalization due to worsening COVID (1 vs 2)]; study discontinued (13 vs 12) [adverse event (2 vs 1), lost to follow-up (2 vs 3), sponsor decision (2 vs 1), withdrawal by patient (4 vs 4), hospitalization due to worsening COVID (1 vs 3), other (2 vs 0)] Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (similar proportions and reasons for missingness between arms). Risk assessed to be some concerns for the outcomes: 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 assessors). The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected outcomes. All these outcomes 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 |
Some concerns |
Comment: The protocol and statistical analysis plan (dated December 9th, 2020) and registry were available. The protocol was retrospective and no information on the changes made to the original document were accessible. The prospective version of the registry (dated June 1st, 2020) was accessible and consulted.
ADVERSE EVENTS 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 outcome: Adverse events. SERIOUS ADVERSE EVENTS. Outcome 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: Serious adverse events. |
Overall risk of bias |
Some concerns |