| Bias | Author's judgement | Support for judgement |
| Randomization |
Some concerns |
Quote: "no specific randomisation was used when allocating participants to the vaccinations schedule cohorts" "The randomisation codes for each vaccination schedule cohort were generated individually, using block randomisation with a block size of six in phase 1 and a block size of five in phase 2, using SAS software (version 9.4). The randomisation code was assigned to each participant in sequence in the order of enrolment, and then the participants received the investigational products labelled with the same code" Comment: No specific randomisation between schedule cohorts. The allocation sequence between vaccine groups and placebo was generated adequately. Unclear allocation concealment. |
| Deviations from intervention |
Low |
Quote: "The vaccine and the placebo are identical in appearance. All participants, investigators, and laboratory staff were masked to treatment allocation." (publication) "Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)" (trial registry) Comment: Blinded study (patients, care providers, and investigators). Data were analyzed using intention-to-treat analysis. |
| Missing outcome data |
Low |
Comment: 600 participants randomized; 600 participants analyzed for adverse evens outcomes; 590 participants analyzed for neutralizing antibody outcomes; 582 participants analyzed for specific antibody outcomes. The rate of missing data was very low (<95%). Risk assessed to be low for the outcomes: Specific antibody seroconversion. Specific antibody geometric mean titres. Neutralizing antibody seroconversion. Neutralizing antibody geometric mean titres. Local adverse events. Systemic adverse events. Solicited adverse events. Unsolicited adverse events. Total Adverse events. |
| Measurement of the outcome |
Low |
Comment: Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Specific antibody seroconversion. Specific antibody geometric mean titres. Neutralizing antibody seroconversion. Neutralizing antibody geometric mean titres. Local adverse events. Systemic adverse events. Solicited adverse events. Unsolicited adverse events. Total Adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan were not available at the time of data extraction. The trial registry was available, and data were analyzed and presented as pre-specified in the trial registry. Risk assessed to be low for the outcomes: Specific antibody seroconversion. Specific antibody geometric mean titres. Neutralizing antibody seroconversion. Neutralizing antibody geometric mean titres. Local adverse events. Systemic adverse events. Solicited adverse events. Unsolicited adverse events. Total Adverse events. |
| Overall risk of bias |
Some concerns |