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 eligible participants were randomized within each age group (18 through 59 years, and 60 years or older) in a ratio of 2:2:1 to receive either 5 μg vaccine, 10 μg vaccine, or placebo. The randomization list was generated by an independent statistician using SAS software (version 9.4; SAS Institute). A unique randomization number in sequence was allocated to each participant, who then received a vaccine or placebo dose labelled with the same randomization number. The individuals involved in randomization and masking had no involvement in the rest of the trial.:
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Double-blind. Participants, investigators, and staff undertaking laboratory testing were blinded to treatment allocation.”
Comment: Blinded study (participants and personnel/carers) ll participants who received at least 1 dose were included in safety analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 500 participants randomized; 500 participants analyzed for safety
Data available for all or nearly all participants randomized for safety. Risk assessed to be low for the outcomes: 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: 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 were available.
Outcomes pre-specified in registry and/or protocol. 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: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Low |