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: "A computerized random number generator performed block randomization with a randomly selected block size of 6, and eligible participants were randomly assigned into three groups"
Comment: Allocation sequence random. No information on allocation concealment. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Comment: No information on blinding (participants and personnel/carers).
Deviations from intended intervention arising because of the study context: No participant cross-over. All participants received two doses. Hence, deviations did not arise because of the trial context. Data for the safety and efficacy outcomes were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. All participants received two doses. Immunogenicity outcomes were assessed in all available particpants. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 809 participants randomized; 809 participants analyzed for safety and efficacy; 744 participants analyzed for immunogenicity and Confirmed COVID after second dose.
Safety and efficacy data available for all participants randomized. Risk assessed to be low for the outcomes: Confirmed COVID after first dose. Local adverse events. Systemic adverse events. Serious adverse events. Data not available for all or nearly all participants randomized for immunogenicity and Confirmed COVID after second dose. No evidence that the result is not biased. Reasons: 3.7%, 6.3% and 8.6% lost to follow up, 1.5%, 2.2% and 1.9% declined to participate at last assessment. 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 some concerns for the outcomes: Neutralizing antibody GMT. |
| 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. Unclear blinding (outcome assessor). NEUTRALIZING ANTIBODY GMT Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Confirmed COVID. Neutralizing antibody GMT. LOCAL, SYSTEMIC, ADVERSE, and SERIOUS 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. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective trial registries were available (dated 2 January 2021).
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: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |