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: “Sequential computer-generated randomization numbers were assigned to participants, and stratified block randomization by age and doses was adopted (block size 8).”
Comment: Allocation sequence random. Unclear allocation concealment. Imbalances in baseline characteristics appear to be compatible with chance. Risk assessed as some concerns |
| Deviations from intervention |
Low |
Quote: “Participants, investigators, and laboratory personnel were blinded to the intervention allocation.”
Comment: Blinded study (participants and personnel/carers) Data for the outcome were analyzed using intention-to-treat analysis. 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: Neutralizing antibody GMT. Specfic antibosy GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 1120 participants randomized; 1120 participants analyzed for safety; 1113 participants analyzed for immunogenicity.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Specfic antibosy GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| 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. Specfic antibosy GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and registry (prospective, dated 2020-04-11) were available.
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. Specfic antibosy GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |