| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: "The participants were sequentially assigned a randomisation number generated by Stata, version 12.0, and stratified block randomisation (block size eight) by subgroups was used, generated by an independent statistician. Individuals involved in randomisation and masking had no involvement in the rest of the trial." Quote: "Vaccine and placebo were distributed in identical packages with serial numbers. Group allocation was concealed from participants, investigators, and outcome assessors." Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: "Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation." Quote: "Vaccine and placebo were distributed in identical packages with serial numbers." Comment: Blinded study (patients and investigators) Comment: No cross-over reported. Quote: "Four participants in the days 0 and 21 schedule and one participant in the days 0 and 28 schedule quit or did not finish taking blood sample at day 28 on request" Comment: This deviations present 3.5% and 0.89% of the n randomized per arm respectively. It is unlikely these deviations could have affected the outcome. Comment: "As treated" analysis used for immunogenicity outcomes. |
| Missing outcome data |
Some concerns |
Comment: 448 randomized; 448 analyzed for safety, 331 analyzed for immunogenicity. 26% missing data. Most of the missing data (25%) was due to only half of the participants from two groups were measured at the 28-day follow-up. Risk assessed to be "some concerns" for the outcome: nAb GMTs. |
| Measurement of the outcome |
Low |
Comment: Double blind study. Risk assessed to be low for the outcome: nAb GMTs. |
| Selection of the reported results |
Low |
Comment: Outcomes reported as pre-specified in the study registry. Protocol and statistical plan not available. Risk assessed to be low for the outcome: nAb GMTs. |
| Overall risk of bias |
Some concerns |