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: "The participants were stratified into two age strata, age 18 – 45 years and 46 – 59 years. The randomization process was performed using a block of two or four in sealed envelope."
Comment: Allocation sequence probably random Unclear allocation concealment Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: “Double-blinded. The vaccination was performed by unblinded nurses. Therefore, the participants and blinded study team were not aware of the randomization arms.”
Comment: Blinded study (participants and personnel/carers) Per-protocol analysis was performed on the outcomes. Reasons for exclusion: For immunogenicity 2/2 were excluded from Anti S-RBD IgG and neutralizing antibodies analyses due to missing data; for safety analysis 3/5 were excluded due to missing data 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 the small number of missing patients. Risk assessed to be some concerns for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Local adverse events. Systemic adverse events. |
| Missing outcome data |
Some concerns |
Comment: 422 participants randomized; 410-418 participants analyzed for specific and neutralizing antibodies; 414 participants analyzed for safety; 80 participants analyzed for cellular response.
Data available for all or nearly all participants randomized for specific and neutralizing antibodies and safety. Data not available for all or nearly all participants randomized for cellular response. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Risk assessed to be some concerns for the outcomes: Cellular response |
| 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: Specific antibody GMT. Neutralizing antibdy GMT. Cellular response. Local adverse events. Systemic adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (July 22, 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 some concerns for the outcome: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Local adverse events. Systemic adverse events. |
| Overall risk of bias |
Some concerns |