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: “We used an interactive web-based response-randomization system for stratified randomization. Randomization lists were generated by an independent statistician using SAS (version 9.4), with a block size of 10.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: “The unblinded staffs who prepared and administered vaccination were aware of the treatment allocation, but were not allowed to involve in any other trial procedures or to reveal this information to any participants or other investigators. Blinding was maintained by preparing vaccines out of sight of participants and other investigators and concealing the syringes with a label of randomization number.”
Comment: Blinded study (participants and personnel/carers). LOCAL ADVERSE EVENTS, SYSTEMIC ADVERSE EVENTS, ADVERSE EVENTS, SERIOUS ADVERSE EVENTS ITT analysis reported for safety outcomes 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. Adverse events. Serious adverse events. NEUTRALIZING ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT OMICRON, SEROCONVERSION NEUTRALIZING ANTIBODY OMICRON The outcomes were assessed in the first 30 participants in each arm. 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 all participants according to their randomized assignment due to preplanned analysis and balance between arms. Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. Neutralizing antibody GMT Omicron. Seroconversion neutralizing antibody Omicron. |
| Missing outcome data |
Low |
Comment: 199 participants randomized; 199 participants analyzed for safety; 95 analyzed for immunogenicity againt the original strain, 60 participants analyzed for immunogenicity against omicron
LOCAL ADVERSE EVENTS, SYSTEMIC ADVERSE EVENTS, ADVERSE EVENTS, SERIOUS ADVERSE EVENTS 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. NEUTRALIZING ANTIBODY GMT Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Outcomes were assessed in a preplanned subgroup of the first 30 participants in each arm. The subsequent risk of bias was already assessed in domain 2. Risk assessed to be low for the outcomes: Neutralizing antibody GMT Omicron. |
| 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. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective protocol (Date April 16th, 2021), statistical analysis plan, registry were available (Date July 7th, 2021).
Outcomes pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Cellular response. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |