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: “Following enrollment, participants were randomly assigned to the three groups by block randomization.”
Comment: Allocation sequence probably random. No information on allocation concealment. |
| Deviations from intervention |
Low |
Quote: “Open-label. Participants and investigators were not blinded during the study period.”
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 immunogenicity outcomes were analyzed using intention-to-treat analysis using available participants. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Specific antibody GMT. Cellular response. Local adverse events. Systemic adverse events. |
| Missing outcome data |
Some concerns |
Comment: 125 participants randomized; 124 participants analyzed for immunogenicity; 98 participants analyzed for safety.
Data available for nearly all participants randomized for immunogenicity. Data not available for all or nearly all participants randomized for safety. No evidence that the result is not biased. Reasons: presumably non-response - safety events were collected in an online form. 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 low for the outcomes: Specific antibody GMT. Cellular response. Risk assessed to be some concerns for the outcomes: Local adverse events. Systemic 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) SPECIFIC ANTIBODY GMT, CELLULAR RESPONSE Observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Specific antibody GMT. Cellular response. LOCAL and SYSTEMIC 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. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available.
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: Specific antibody GMT. Cellular response. Local adverse events. Systemic adverse events. |
| Overall risk of bias |
Some concerns |