Trial jRCT2051210164
Publication Akahata W , SSRN, 2023
Primary outcome on the report: Neutralising antibody titres against SARS-CoV-2 variants up to 4 weeks after study drug administration; Occurrence of solicited local and systemic adverse events that occurred up to 6 days (Day 7) after study drug administration, and any unsolicited adverse events that occurred up to 4 weeks after study drug administration.

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 principal investigator appointed a study drug randomization supervisor who prepared the randomization schedule prior to participant enrolment and was responsible for storing and managing it until study unblinding. Potential participants were assigned a screening number by the principal or sub investigator, assessed for suitability to participate in the study, and upon completion of screening, were allocated a participant identification code. Participants were stratified into two age subgroups: 18 to 55 years (non-elderly cohort) and ≥65 years (elderly cohort)"
Comment: Allocation probably random.
Unclear allocation concealment.
Deviations from intervention
Some concerns 		Quote: “Assessors and participants were blinded for the study. The principal investigator assigned unblinded medical staff in advance who allocated, prepared and administered the study drugs and were not involved in the assessments of participants after administration.”
Comment: Unblinded study (participants blinded, personnel/carers unblinded)
Deviations from intended intervention arising because of the study context: 12 participants received other authorized COVID-19 vaccines (3 vs 4 vs 1 vs 1 vs 3).
This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect.
ITT analysis (with N randomized denominators)
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 some concerns for the outcomes: Adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: 46 participants randomized; 46 participants analyzed.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: 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: Adverse events. Serious adverse events.
Selection of the reported results
Some concerns 		Comment: The restrospective protocol and statistical analysis plan (May 13,2022), and the prospective registry were available (dated Feb. 01, 2022)

ADVERSE EVENTS
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: Adverse events.

SERIOUS ADVERSE EVENTS
Outcome not pre-specified in the prospective registry and no prospective protocol available
No information on whether the result was selected from multiple outcome measurements or analyses of the data.
Trial not analyzed as pre-specified.
Risk assessed to be some concerns for the outcome: Confirmed COVID.Serious adverse events.
Overall risk of bias
Some concerns