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: “All participants were randomly assigned to study intervention using an interactive web response system (IWRS).”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: “Double-blinding was employed in the study; hence, both participants and investig.ators were blinded to the participants’ assignment of the study intervention.”
Comment: Blinded study (participants and personnel/carers) MORTALITY The outcome was analyzed on 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 outcome: Mortality. LOCAL ADVERSE EVENTS. SYSTEMIC ADVERSE EVENTS. ADVERSE EVENTS. SERIOUS ADVERSE EVENTS Safety analysis on 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: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. SPECIFIC ANTIBODY GMT. NEUTRALIZING ANTIBODY GMT Immunogencity outcomes were analyzed in a sub-set of particpants who had received two doses of the study intervention, had valid154 immunogenicity data on Day 43, and had no major protocol deviations up to Day 43. As we are assessing the effect of assignment to intervention, the analysis method performed on these safety outcomes, was considered inappropriate. 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:Specific antibody GMT. Neutralizing antibody GMT. |
| Missing outcome data |
Low |
Comment: 1030 participants randomized; 1030 participants analyzed for mortality and safety outcomes; 326 participants analyzed for Specific antibody GMT; 83 particpants analyzed for Neutralizing antibody GMT.
MORTALITY. LOCAL ADVERSE EVENTS. SYSTEMIC ADVERSE EVENTS. ADVERSE EVENTS. SERIOUS ADVERSE EVENTS Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. SPECIFIC ANTIBODY GMT. NEUTRALIZING ANTIBODY GMT Data not available for all or nearly all participants randomized for immunogenicity, but this potential risk of bias has been taken into account in domain 2. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. |
| 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 prospective registry was available (Date August 18, 2021).
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. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |