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: "At enrollment on Day 1 participants were randomly allocated 1:1 using an interactive voice response system (IVRS), interactive web response system (IWRS), or interactive response technology (IRT)."
Comment: Allocation sequence random Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: "Participants were blinded to which vaccine they received which was administered by study nurses who played no further role in the study. All subsequent steps, including laboratory analyses, were performed in a blinded manner."
Comment: Blinded study (participants and personnel/carers) MORTALITY. ADVERSE EVENTS.SERIOUS ADVERSE EVENTS Safety outcomes analysis included those who received at least one dose of the intervention 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. Serious adverse events. NEUTRALIZING ANTIBODY GMT. NEUTRALIZING ANTIBODY GMT OMICRON. nAb SEROCONVERSION RATE OMICRON Per-protocol analysis was performed on the immunogenicity outcomes. Reasons for exclusion: 1 participant in the SCB-2019 group vs 2 participants in the CoronaVac group failed to provide a Day 15 blood sample; 3 participants in each group failed entry criteria and 1 in the SCB-2019 was out of schedule. 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 the small n. Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. Neutralizing antibody GMT OMICRON. nAb Seroconversion rate Omicron NEUTRALIZING ANTIBODY GMT OMICRON. nAb SEROCONVERSION RATE OMICRON Quote: "Secondary immunogenicity objectives were to evaluate the neutralizing responses against SARS-CoV-2 variants in subsets of participants from homologous and heterologous groups" Immunogenicity outcomes against variants were assessed and analyzed in a sub-set of participants. 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 arms. Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT OMICRON. nAb Seroconversion rate Omicron |
| Missing outcome data |
Low |
Comment: 430 participants randomized; 430 participants analyzed for safety; 420 participants analyzed for immunogenicity against ancestral strain; 99 participants analyzed for immunogenicity against Omicron variant
Data available for all or nearly all participants randomized for sqfety outcomes. Data not available for all participants randomized for immunogenicity outcome. However, reasons for missigness wwere already assessed in Domain 2. Risk assessed to be low for the outcomes: Mortality. Neutralizing antibody GMT. nAb Seroconversion rate. Neutralizing antibody GMT Omicron. nAb Seroconversion rate Omicron. 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: Mortality. Neutralizing antibody GMT. nAb Seroconversion rate. Neutralizing antibody GMT Omicron. nAb GMT seroconversion rate Omicron. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The registry was available (dated January 12, 2022).
MORTALITY. NEUTRALIZING ANTIBODY GMT. ADVERSE EVENTS.SERIOUS ADVERSE EVENTS. 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 low for the outcomes: Mortality. Neutralizing antibody GMT. Adverse events. Serious adverse events. NEUTRALIZING ANTIBODY GMT OMICRON. nAb SEROCONVERSION OMICRON Outcome not pre-specified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: nAb GMT-Omicron, nAb seroconversion-Omicron. |
| Overall risk of bias |
Some concerns |