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:"An automatically randomised list was prepared by a biostatistician using an internet resource. The randomisation was stratified by age (18–59 and ≥60 years) and time since last primary dose (3 to <6 months and 6 to 9 months). Each participant was assigned a unique study identification number and randomisation code (A, B, C, D, or E). Participants were randomly assigned and vaccinated by the unmasked personnel."
Comment: Allocation sequence random Unclear allocation concealment. Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: "observer and participant masked"
Comment: Blinded study (blinded participants and unblinded 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. LOCAL ADVERSE EVENTS, SYSTEMIC ADVERSE EVENTS, SERIOUS ADVERSE EVENTS Safety analysis conducted on all participants that completed the vaccination protocol. 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: Local adverse events. Systemic adverse events. Serious adverse events. SPECIFIC ANTIBODY GMT Per-protocol analysis was performed on the immunogenicity outcomes. Reasons for exclusion: four had a major protocol deviation. 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 of missing participants. Risk assessed to be some concerns for the outcomes: Specific antibody GMT. |
| Missing outcome data |
Low |
Comment: 960 participants randomized; 957 participants analyzed for local/system safety; 953 participants analyzed for 28 day safety, efficacy and mortality; 949 participants analyzed for immunogenicity.
Data available for all or nearly all participants randomized. Risk assessed to below for the outcomes: Specific antibody GMT. Local adverse events. Systemic 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: Specific antibody GMT. Local adverse events. Systemic adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and prospective registry were available (Dated Nov 25th, 2021)
Outcome pre-specified for immunogenicity and safety. 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: Specific antibody GMT. Local adverse events. Systemic adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |