Trial NCT04677660
Publication Masuda T, Vaccine, 2022
Primary outcome on the report: 1) solicited AEs through 7 days after each vaccination; 2) unsolicited AEs through 28 days after each vaccination; 3) MAAEs, SAEs, AEs leading to discontinuation of vaccination and AEs leading to participant withdrawal from the trial through day 57; 4) proportion of participants with SARS-CoV-2 infection through day 57; 5) serum bAb levels against SARS-CoV-2 on day 57

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: "randomisation tables generated by sponsor randomisation personnel or an unblinded designee"
Comment: Allocation sequence probably random.
No information on allocation concealment.
Deviations from intervention
Some concerns 		Quote: “participants, data collectors (e.g. investigators) and data evaluators were blinded to the trial-group assignment. Designated site personnel had access to the trial-group assignments to manage and prepare the trial vaccines but were not involved in data collection or safety evaluation after vaccine administration”
Comment: Blinded study (participants and personnel/carers).
Intention-to-treat analysis was carried out on safety 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: Mortality. Local adverse events. Adverse events. Withdrawals due to adverse events. Serious adverse events.
Per-protocol analysis was performed on the immunogenicity outcomes.
Reasons for exclusion: 3 in vaccine arm because they did not receive a second vaccination; 1 in placebo arm because their day 57 visit could not be completed by the data cut-off date.
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 due to the small proportion excluded.
Risk assessed to be some concerns for the outcomes: Specific antibody GMT. Neutralizing antibody GMT.
Missing outcome data
Low 		Comment: 200 participants randomized; 200 participants analyzed for safety; 196 participants analyzed for immunogenicity.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. 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: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Adverse events. Withdrawals due to adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective registry was available.
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 outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Adverse events. Withdrawals due to adverse events. Serious adverse events.
Overall risk of bias
Some concerns