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 |
|
Quote: “the subjects in each procedure were randomly assigned at a 2:2:1 ratio”. Comment: No information on random sequence generation or allocation concealment. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "Double-blind, placebo-controlled" (paper) "Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)" (trial tegistry) Comment: Blinded study (patients and physicians). Data were analyzed using intention-to-treat analysis. |
| Missing outcome data |
Low |
Comment: 750 randomized; 750 analyzed for adverse events; 745 analyzed for Seroconversion and GMTs. No attrition for adverse events, very low (0.7%) attrition rate for immunogenicity outcomes. Risk assessed to be low for the outcomes: Neutralizing and specific antibody seroconversion. Neutralizing and specific antibody geometric mean titres. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Neutralizing and specific antibody seroconversion. Neutralizing and specific antibody geometric mean titres. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: Neither the protocol nor the statistical analysis plan was available. The trial registry was available and there were few differences between the published article and registration in population, procedures, interventions and outcomes. Only 12-month safety outcomes and cellular immune response were not reported. For the former the timepoint has not been reached. Risk assessed to be low for the outcomes: Neutralizing and specific antibody seroconversion. Neutralizing and specific antibody geometric mean titres. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |