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: "The trial staff administering the vaccine prepared vaccines out of sight of the participants and syringes were covered with an opaque material until ready for administration to ensure blinding of participants ... Clinical investigators involved in endpoint assessment and the laboratory team remained blinded to group allocation."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quotes: "participant-blinded" “Clinical investigators involved in endpoint assessment and the laboratory team remained blinded to group allocation.”
Comment: Blinded study (participants and personnel/carers). SAFETY Intention-to-treat analysis was carried out for safety outcomes. As we are assessing the effect of assignment to intervention, the analysis method performed on these outcomes was considered appropriate. Risk assessed to be low for the outcomes: Adverse events. Serious adverse events. IMMUNOGENICITY Per-protocol analysis was performed on immunogenicity outcomes. Reasons for exclusion: seropositive at baseline (n = 4/0/5/1). 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 balance between excluded participants. Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. Cellular response. |
| Missing outcome data |
Some concerns |
Comment: 150 participants randomized; 150 participants analyzed for safety and efficacy; 119 participants analyzed for neutralizing antibody GMTs within the 127-participant seronegative set; 93 participants analyzed for cellular response within the 127-participant seronegative set.
SAFETY Safety data available for all participants randomized. Risk assessed to be low for the outcomes: Adverse events. Serious adverse events. IMMUNOGENICITY Immunogenicity data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons for missing data were not reported. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome because proportions of missing data between arms were similar. Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. Cellular response. |
| 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: Neutralizing antibody GMT. Cellular response. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, registry were available.
If data analyzed and presented as pre-specified
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 some concerns for the outcomes: Neutralizing antibody GMT. Cellular response. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |