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 occurred after all screening-related activities were completed and prior to the first dose of study vaccine using the interactive web response system (IWRS) platform. A randomization scheme was generated by using a validated system.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “a single-blind study where study participants randomized into immunogenicity arm are kept blinded of the vaccination group to which they have been assigned, but the investigator and study staff are aware of the assigned group.”
Comment: Partially blinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Hence, deviations did not arise because of the trial context. Data for the safety outcomes were analyzed using modified intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Data for neutralizing antibodies were analyzed in a predefined randomized immunogenicity cohort. Data for cellular response were analyzed in a randomly selected sub-set of the immunogenicity cohort. 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 randomized selection of the sub-set. 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 |
Low |
Comment: 2140 participants randomized; 2139 participants analyzed for safety; 610/640 analyzed for neutralizing antibodies; 106 participants analyzed for cellular response.
Data available for all or nearly all participants randomized for safety and neutralizing antibodies. Data not available for all or nearly all participants randomized for cellular response, but this potential source of bias has been taken into account in domain 2. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| 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. Unblinded study (outcome assessor) NEUTRALIZING ANTIBODY GMT Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: 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 registry was available.
Safety and neutralizing antibodies outcomes pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified for safety and neutralizing antibodies. Cellular response outcome not pre-specified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified for cellular response. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |