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: "Permuted block randomization was used to stratify according to study sites and age groups (18 to < 55 years and > 55 years) using an interactive web response system."
Comment: Allocation sequence probably random. Allocation sequence probably concealed. Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: “After the randomization, each participant received the assigned intervention via intramuscular injection in the deltoid region by predetermined unblinded site staff who were not involved in the assessment and evaluation of participants. The remaining site staff,study participants, and sponsor were blinded to the study treatment.”
Comment: Blinded study (participants and personnel/carers) MORTALITY All the participants who received intervention were analyzed 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 outcome: Mortality. SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY ASSAY GMT, NEUTRALIZING ANTIBODY ASSAY GMT OMICRON Per-protocol analysis was performed on the outcomes Reasons for exclusion: Participants with invalid laboratory data and anti-N positive (prior infection/history of COVID-19) or major protocol deviation were excluded of the analysis of the oucomes: Specific antibody GMT and Neutralizing antibody assay GMT. A pre-specified subset of participants was analyzed for the outcomes: Seroconvertion rate Omicron and Neutralizing antibody assay GMT Omicron. 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 exclusions balanced between arms. Risk assessed to be some concerns for the outcomes: Specific antibody GMT, Neutralizing antibody assay GMT, Neutralizing antibody assay GMT Omicron. |
| Missing outcome data |
Some concerns |
Comment: 323 participants randomized; 323 participants analyzed for mortality, 309 participants analyzed for Specific antibody GMT and Neutralizing antibody assay GMT, unknown number of participants analyzed for Neutralizing antibody assay GMT Omicron.
MORTALITY, SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY ASSAY GMT Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality, Specific antibody GMT and Neutralizing antibody assay GMT NEUTRALIZING ANTIBODY ASSAY GMT OMICRON No information on whether data were available for all randomized participants. No evidence that the result is not biased. No information on whether missingness could or is likely to depend on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Neutralizing antibody assay GMT 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: Mortality, Specific antibody GMT and Neutralizing antibody assay GMT and Neutralizing antibody assay GMT Omicron. |
| Selection of the reported results |
Low |
Comment: The registry was available (January 19, 2022)
SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY ASSAY GMT, NEUTRALIZING ANTIBODY ASSAY GMT OMICRON 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: Specific antibody GMT, Neutralizing antibody assay GMT Omicron. MORTALITY 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. Trial analyzed as pre-specified. Risk assessed to be low for the outcome:Mortality. |
| Overall risk of bias |
Some concerns |