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: “centrally randomized to study intervention using an interactive web response system (IWRS)”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Low |
Quote: “This is a double-blinded study. Neither participants, nor investigators, nor the sponsor study team will be aware of treatment assignments prior to the final data base lock at the conclusion of the study.”
Comment: Unclear blinding (participants blinded and unclear if personnel/carers blinded) Deviations from intended intervention arising because of the study context: No patient cross-over (gained from contact with authors) 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 outcome is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcome: Hospitalization or death. |
| Missing outcome data |
Low |
Comment: 467 participants randomized; 452 participants analyzed for all outcomes except viral negative conversion events (461 analyzed).
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcome: Hospitalization or death. |
| Measurement of the outcome |
Low |
Quote: “This is a double-blinded study. Neither participants, nor investigators, nor the sponsor study team will be aware of treatment assignments prior to the final data base lock at the conclusion of the study.”
Response from contact with authors: "The study outcomes were assessed by the sponsor at pre-specified timing of interim analysis, when each cohort of patients have had an opportunity to reach the primary endpoint for that cohort. The method of assessment for each endpoint is described in the study protocol and SAP (Statistical Analysis Plan)." Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcome: Hospitalization or death. |
| Selection of the reported results |
Low |
Comment: The prospective protocol (dated May 30th, 2020) and statistical analysis plan and registry were available.
HOSPITALIZATION OR DEATH Outcome pre-specified. Results were not selected from multiple outcome measurements or multiple analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality (D28). Hospitalization or death. Adverse events. Serious adverse events. |
| Overall risk of bias |
Low |