| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: "The randomisation codes for phases 1 and 2 were generated by the randomisation statistician, using block randomisation and SAS software (version 9.4). The randomisation code was assigned to each participant in sequence in order of enrolment, and participants received the study vaccine or placebo labelled with the same code." (report) "All trial vaccines and placebos will be pasted with blind labels" (protocol) "Personnel who conduct blinding are forbidden to participate in other relevant work of this clinical trial, and should not disclose the blinding code to any person participating in this clinical trial." (protocol) Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Low |
Quote: The vaccine and placebo were completely identical in appearance, and all participants, investigators, and laboratory staff were masked to group allocation. Comment: Blinded study (patients and investigators). Two participants (0.5%) crossed over to a different group due to mistakenly receiving an intervention they were not assigned to. As-treated analysis was used for safety outcomes, but the proportion moved to another group was negligible. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Total adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: Data from interim analysis Comment: 422 participants randomized; 421 participants analyzed. Data available for all or nearly all participants Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Total 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. Quote: After unblinding, the investigators responsible for the observation and evaluation of the subjects and the CRAs responsible for the source data verification should be kept blind until the database is finally locked. (Protocol) Comment: Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Total adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and registry were available. 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 outcomes: Local adverse events. Systemic adverse events. Total adverse events. Serious adverse events. |
| Overall risk of bias |
Low |