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 |
Some concerns |
Quote: “Prospective, multi-centre, randomized, observer-blinded Phase 2 study.”
Comment: Allocation sequence probably random. No information on allocation concealment. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: “Observer blinded” “Double (Participant, Investigator)”
Comment: Blinded study (participants and personnel/carers). SERIOUS ADVERSE EVENTS Safety analyses included all randomized participants with at least one vaccination dose. 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 low for the outcomes: Serious adverse events. NEUTRALIZING ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT (>90D), NEUTRALIZING SEROCONVERSION RATE OMICRON, NEUTRALIZING ANTIBODY GMT OMICRON Per-protocol analysis was performed on the immunogenicity outcomes. Reasons for exclusion: nAb was only measured in a subgroup of participants. As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There was probably no substantial impact of failure to analyze participants according to their randomized assignment due to balance between groups (sAb, nAb). Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. Neutralizing antibody GMT (>90 days). Neutralizing seroconversion rate Omicron. Neutralizing antibody GMT Omicron. |
| Missing outcome data |
Low |
Comment: 1243 participants randomized; 1243 participants analyzed for safety; 396-1233 participants analyzed for immunogenicity.
SERIOUS ADVERSE EVENTS Data available for all or nearly all participants randomized for safety. Risk assessed to be low for the outcomes: Local adverse events. Serious adverse events. NEUTRALIZING ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT (>90D), NEUTRALIZING SEROCONVERSION RATE OMICRON, NEUTRALIZING ANTIBODY GMT OMICRON Data not available for all or nearly all participants randomized for immunogenicity. No evidence that the result is not biased. Reasons: sAb: COVID-19 infection, receipt of a fourth vaccine dose, immunocompromised state; nAb was only measured in a subgroup of participants. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. This potential source of bias has been taken into account in domain 2. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Neutralizing antibody GMT (>90 days). Neutralizing seroconversion rate Omicron. |
| Measurement of the outcome |
Low |
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 outcomes: Neutralizing antibody GMT. Neutralizing antibody GMT (>90 days). Neutralizing seroconversion rate Omicron. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (dated September 20, 2021).
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 outcomes: Neutralizing antibody GMT. Neutralizing antibody GMT (>90 days). Neutralizing seroconversion rate Omicron. Serious adverse events. |
| Overall risk of bias |
Some concerns |