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: “participants were randomly allocated”
Comment: Allocation sequence probably random. No information on allocation concealment. |
| Deviations from intervention |
|
Quote: “Open-label”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Pre-planned per-protocol analysis was performed on the immunogenicity outcomes. Reasons for exclusion: losses to follow up/withdrawals 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 balanced losses to follow up between arms. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. |
| Missing outcome data |
Some concerns |
Comment: 113 participants randomized; 96 participants analyzed for safety; 106-109 participants analyzed for immunogenicity.
Data not available for all or nearly all participants randomized for immunogenicity (nAb). No evidence that the result is not biased. Reasons: losses to follow up/withdrawals. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Risk assessed to be some concerns for the outcome: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY, IMMUNOGENICITY Mortality and immunogenicity are observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. ADVERSE EVENTS The authors reported on adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Local adverse events. Systemic adverse events. Adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registries were available.
Outcomes 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: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. |
| Overall risk of bias |
Some concerns |