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: "In this study, participants whose eligibility was confirmed were randomly allocated to the S-268019-b group or the tozinameran group at 1:1 ratio by the study intervention allocation manager or the person in charge of allocation designated by the study intervention allocation manager. Participants were stratified by age (<40 years and ≥40 years) and sex. The allocation table was prepared by the permuted block randomization with a block size of 4 in each of the 4 strata. The study intervention allocation manager prepared a separate protocol for randomization and complied with it."
Comment: Allocation sequence random. No information on allocation concealment. |
Deviations from intervention |
Low |
Quote: “Observer-blinded”
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over. Hence, deviations did not arise because of the trial context. Data for the safety outcomes were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Per-protocol analysis was performed on the immunogenicity outcomes. Reasons for exclusion: confirmed positive anti-SARS-CoV-2 N-protein antibody test at screening or after the booster dose. 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 small numbers. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
Missing outcome data |
Low |
Comment: 206 participants enrolled; 204 participants randomized; 204 participants analyzed for safety; 202 participants analyzed for immunogenicity.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody 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: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
Selection of the reported results |
Some concerns |
Comment: The prospective trial registry was available (dated 6.12.2021).
Neutralizing antibody GMT outcome was pre-specified. Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Results were probably not selected from multiple outcome measurements or analyses of the data. Risk assessed to be low for the outcomes: Mortality. Neutralizing antibody GMT. Specific antibody GMT and adverse events outcomes were not pre-specified in the trial registry. 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 outcomes: Specific antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
Overall risk of bias |
Some concerns |