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: “The randomization sheets were generated by the trial statistician. All new randomization sheets and all updates of existing randomization sheets were done using a pre-written R script which was stored on the randomization Dropbox folder (owner is MORU, under custodianship of the head of MORU IT); this file is a full ‘Professional’ version with history recorded and only the trial statistician and head of IT had access..
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: Two participants in. the SC arm crossed-over to another treatment arm in the platform study. 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. In the outpatient setting, we consider no important cointerventions of interest. Hence, no deviation arose because of the trial context. Our analysis for the binary safety outcomes 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). WHO score 7 and above (D28). Serious adverse events. |
| Missing outcome data |
Low |
Comment: 136 participants randomized; 136 participants analyzed for safety; 2 missing data (withdrew).
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). WHO score 7 and above (D28). 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). 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 outcome: WHO score 7 and above (D28). SERIOUS ADVERSE EVENTS The authors reported on 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 outcome: Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The prospective protocol, statistical analysis plan and registry (dated September 13, 2021) were available.
MORTALITY Mortality outcome was not pre-specified in the protocol/SAP/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 (D28). WHO SCORE 7 AND ABOVE, 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 outcomes: WHO score 7 and above (D28). Serious adverse events. |
| Overall risk of bias |
Some concerns |