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: "The interactive web response system (IWRS) assigned a unique intervention code, which dictated the
intervention assignment for the participant." (from report)
Quote: "Method of Generating Random Sequence:Computer generated randomization Method of Concealment: On-site computer system" (from registry) Comment: Allocation sequence random Allocation sequence concealed No information about imbalances in baseline characteristics (data were not reported by arm) |
| Deviations from intervention |
Low |
Quote: “Except independent statistician from contract
research organization (CRO) and personnel responsible for conducting
packaging/labelling/blinding of the investigational product, all the personnel involved in the
study remained blinded to the study vaccine”
Comment: Blinded study (participants, outcome asesor and personnel/carers) ADVERSE EVENTS,SERIOUS ADVERSE EVENTS Quote:"All safety-related tabulations and analyses were performed on safety population (subjects who received at least one dose of any study vaccine)" 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:Mortality. Adverse events. Serious adverse events NEUTRALIZING ANTIBODY GMT ASSAY Quote:"The primary immunogenicity analysis was performed in the per-protocol population (participants who received the single booster dose and for whom protocol specified immunogenicity data was available)" Per-protocol analysis was performed on the outcomes. There were no participants excluded from the analysis As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There was no substantial impact of failure to analyze participants according to their randomized assignment since there was no creoss-over or exclusion from the analysis Risk assessed to be low for the outcomes: Neutralizing antibody GMT. |
| Missing outcome data |
Low |
Comment: 208 participants randomized; 208 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality. Neutralizing antibody GMT. 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. Neutralizing antibody GMT. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The registry was available (dated 12/01/2022).
NEUTRALIZING ANTIBODIES GMT. ADVERSE EVENTS. SERIOUS ADVERSE EVENTS. 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 outcome: Neutralizing antibody GMT. Adverse events. Serious adverse events. 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 |
Low |