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: “Computer randomization was done with full allocation concealment within the secure web platform used for the study electronic case report form (service provided by Medprove company).”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: “Double blind. Trial staffs responsible for the vaccine preparation and administration, and participants were unaware of vaccine assignment.”
Comment: Blinded study (participants and personnel/carers) Per-protocol analysis was performed on the outcomes. Reasons for exclusion: protocol deviation (0 vs 1 vs 1 vs 1), loss to follow-up (1 vs 0 vs 0 vs 0), did not meet injection criteria (1 vs 0 vs 0 vs 0), withdrew consent (1 vs 0 vs 0 vs 0). 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 small number The outcome Neutralizing antibody GMT was assessed on a group of 112 participants randomly selected (32 VS 32 VS 32 VS 12) (pre-specified in the protocol). Quote:"112 serum samples of groups 2.1 to 2.4 were randomly selected for PRNT 50" Risk assessed to be some concerns for the outcomes: Local adverse events. Systemic adverse events. Neutralizing antibody GMT. |
| Missing outcome data |
Low |
Comment: 560 participants randomized; 554 participants analyzed for safety outcomes; 112 participants analyzed for immunogenicity outcomes.
Data available for nearly all participants randomized for the safety outcomes. Data not availaboe for all participants randomized for immunogenicity outcomes but the reason for the missigness was already assessed in the domain 2. Risk assessed to be low for the outcomes: Neutralizing antibody GMT.Local adverse events. Systemic 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: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective trial registry was available (dated 24 December 2020).
Outcomes were 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. |
| Overall risk of bias |
Some concerns |