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: "Participants in both cohorts were randomised via an Interactive Web Response system (IWRS). The randomisation scheme was generated by independent personnel at the contract research organisation (CRO) using SAS software version 9.4 or later by interactive response technology, which linked sequential randomisation numbers to treatment allocation."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "In this observer-blind study, vaccine group allocation was concealed from all participants and study personnel involved in endpoint assessments. Designated study personnel involved in obtaining randomisation codes from the IWRS and preparing and administering vaccines were not blinded to participant allocation. These personnel did not perform any study evaluations. Additionally, study monitors and statisticians could access unblinded subject-level data as required. All other study personnel, sponsors, CRO staff, statisticians and laboratory personnel involved in immunological testing were blinded to participant allocation."
Comment: Blinded study (participants and personnel/carers). Data for the outcome were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 401 participants randomized; 400 participants analyzed for safety and efficacy outcomes; minimum of 386 participants analyzed for immunogenicity outcomes.
Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. 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. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical plan and trial registry were available (registered prospectively on 15 August 2020).
Specific antibody GMT, adverse events, serious adverse events, and local- and systemic adverse event outcomes were pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified for these outcomes. Risk assessed to be low for the outcomes: Specific antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Results on mortality were probably not selected from multiple outcome measurements or analyses of the data. Risk assessed to be low for the outcome: Mortality. Outcomes were not pre-specified for neutralizing antbody GMTs. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified for this outcome. Risk assessed to be some concerns for the outcome: Neutralizing antibody GMT. |
| Overall risk of bias |
Low |