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: "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 |
Low |
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) No participant cross-over. Hence, deviations did not arise because of the trial context. ITT analysis was performed on the outcomes. As we are assessing the effect of assignment to intervention, the analysis method performed on these safety outcomes, was considered appropriate. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events.Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 448 randomized; 448 analyzed for safety, 331 analyzed for immunogenicity.
All participants randomized were analyzed for the safety outcomes. 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 low for the outcomes: Local adverse events. Systemic adverse events. Adverse events.Serious adverse events. Risk assessed to be "some concerns" for the outcome: nAb GMTs. |
| Measurement of the outcome |
Low |
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. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (2020/4/29).
Outcome 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 outcome: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |