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: "Randomization during both parts was performed using an interactive response technology... Enrollment was observer-blinded to treatment assignment because the study vaccines differed in appearance. Dose preparation, administration, and accountability was performed by designated site personnel who did not participate in any clinical study evaluations. The unblinded site personnel prepared the dose out of view of the participant as well as blinded site personnel, and did not reveal the identity of the study vaccine except in case of emergency."
Comment: Allocation sequence random. Allocation sequence probably concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: "observer-blinded" trial.
Comment: Blinded study (participants and personnel/carers). MORTALITY.ADVERSE EVENTS. SERIOUS ADVERSE EVENTS ITT analysis. 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: Mortality, Adverse events and Serious adverse events. NEUTRALIZING ANTIBODY SEROCONVERSION OMICRON Per-protocol analysis was performed on the outcomes. Reasons for exclusion: 47 vs 43 participants excluded due to baseline SARS-CoV-2 positivity; and additionally for immunogenicity 32 vs 30 excluded due to 28-day SARS-CoV-2 positivity. 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 similar proportions between groups. Risk assessed to be some concerns for the outcome:Neutralizing antibody Seroconversion Omicron. |
| Missing outcome data |
Low |
Comment: 724 participants randomized; 724 participants analyzed for safety; 551 analyzed for immunogenicity.
MORTALITY.ADVERSE EVENTS. SERIOUS ADVERSE EVENTS Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality, Adverse events and Serious adverse events. NEUTRALIZING ANTIBODY SEROCONVERSION OMICRON Data not available for nearly all participants randomized. No evidence that the result is not biased. Reasons: most exclusions already accounted for in domain 2. Missingness could not depend on the true value of the outcome. Risk assessed to be low for the outcome: Neutralizing antibody Seroconversions. |
| 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: Mortality, Neutralizing antibody Seroconversion Omicron, Adverse events and Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The NCT registry was available (dated February 22, 2022).
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, Neutralizing antibody Seroconversion Omicron, Adverse events and Serious adverse events. |
| Overall risk of bias |
Some concerns |