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: "A random table was generated by statisticians using SAS statistical software (version 9.4, SAS Institute Inc., USA). Participants were randomly assigned to each group by a randomized block design, with a block of six and rand of five. Investigators assigned random numbers to eligible participants according to the order of the screening sequence. Experimental vaccines or placebos were obtained and administered according to these random numbers. Statisticians were not allowed to disclose the masking code to any personnel in the clinical trials."
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: "The vaccine and placebo were identical in appearance. The participants, investigators, and laboratory staffs were all masked to group allocation during the trial."
Comment: Blinded study (participants, personnel, investigators). All randomized participants were analysed for safety outcomes and all randomized participants who received at least one dose were analysed for immunogenicity outcomes. As we are assessing the effect of assignment to intervention, the analysis method performed on these outcomes was considered appropriate. Risk assessed to be low for the outcomes: Specific antibody seroconversion. Neutralizing antibody seroconversion. Local adverse events. Systemic adverse events. Unsolicited adverse events. Total adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 180 participants randomized; 180 participants analyzed for safety; 175 participants analyzed for immunogenicity.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Specific antibody seroconversion. Neutralizing antibody seroconversion. Local adverse events. Systemic adverse events. Unsolicited adverse events. Total adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Specific antibody seroconversion. Neutralizing antibody seroconversion. Local adverse events. Systemic adverse events. Unsolicited adverse events. Total adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The registry was available but was retrospective (registered 1.5 months after recruitment started and 1 week after recruitment was completed).
Outcome not pre-specified since registry was retrospective. No information on whether the result was selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Specific antibody seroconversion. Neutralizing antibody seroconversion. Local adverse events. Systemic adverse events. Unsolicited adverse events. Total adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |