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 |
Some concerns |
Quote: "The participants
were sequentially assigned a computer-generated randomizationnumber,
and stratified block randomization (block
size, 8) by subgroups was adopted. Within each randomization
block, the ratio of vaccine vs placebo was 3:1. All the vaccines
and placebos were supplied in coded, identicalappearing,
single-dose vials." Comment: Allocation sequence probably random. Unclear allocation concealment. Risk assessed to be some concerns. |
| Deviations from intervention |
Low |
Quote: "All the vaccines and placebos were supplied in coded, identical-appearing, single-dose vials."
Comment: Blinded study (participants and personnel/carers) SAFEETY The safety analysis was performed on data from all participants who received at least 1 dose. 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: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. IMMUNOGENICITY Quote: "Immunogenicity population is defined as randomized participants who nreceived at least 1 dose injection with nonmissing immunogenicity data before or after injections. All participants in the phase 1 trial and the first half of the participants in the phase 2 trial were scheduled for the hormoral immunogenicity measurement, and there were no missing data" As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There was probably no substantial impact of failure to analyze participants according to their randomized assignment dur to balance between the 2 arms and the absence of exclusions. Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. Specific antibody GMT. |
| Missing outcome data |
Low |
Comment: 224 randomized / 224 analysed (safety) / 112 (immunogenicity).
SAFETY Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. IMMUNOGENICITY Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons for missigness already assessed on domain 2 Missingness could not depend on the true value of the outcome. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Specific antibody GMT. |
| 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 GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events |
| Selection of the reported results |
Low |
Comment: Prospective trial protocol and statistical analysis plan available (March 19, 2020).
Outcomes 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 outcomes: Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |