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: "We used a web-based interactive response randomization system for stratified randomization of the
participants in cohort 1 and cohort 2, respectively... The randomisation lists were generated by an independent statistician using SAS (version 9.4)."
Comment: Allocation sequence random. Allocation sequence probably concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: "open-label" trial.
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: Unclear information on participant cross-over. Hence, no information on whether deviations arose because of the trial context. ITT analysis (with N randomized denominators) or safety analysis on those who received at least one dose of the intervention. As we are assessing the effect of assignment to intervention, the analysis method performed on these safety outcomes, was considered appropriate. Risk assessed to be some concerns for the outcomes: Mortality, nAb Seroconversion rate, Neutralizing antibody GMT, nAb Seroconversion rate Omicron, nAb Seroconversion rate Omicron, Adverse events, and Serious adverse events. |
| Missing outcome data |
Low |
Comment: 356 participants randomized; 356 participants analyzed for safety; 351 (99%) analyzed for immunogenicity.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality, nAb Seroconversion rate, Neutralizing antibody GMT, nAb Seroconversion rate Omicron, Neutralizing antibody GMT Omicron, Adverse events, and 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, NEUTRALIZING ANTIBODY GMT, SEROCONVERSION Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality, nAb Seroconversion rate, Neutralizing antibody GMT, nAb Seroconversion rate Omicron, Neutralizing antibody GMT Omicron. ADVERSE and SERIOUS ADVERSE EVENTS The authors reported on 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 |
Some concerns |
Comment: The prospective registry was available (dated March 31, 2022).
MORTALITY, NAB SEROCONVERSION RATE, NAB GMT OMICRON, NAB SEROCONVERSION RATE OMICRON, ADVERSE EVENTS, AND SERIOUS 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 outcomes: Mortality, nAb Seroconversion rate, nAb GMT Omicron, nAb Seroconversion rate Omicron, Adverse events, and Serious adverse events. Neutralizing antibody GMT ratio (GMR) Outcome not pre-specified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Neutralizing antibody GMR. |
| Overall risk of bias |
Some concerns |