Trial NCT05096832
Publication Wang X-Y, Emerg Microbes Infec, 2022
Primary outcome on the report: 1) Confirmed symptomatic SARS-CoV- 2 infection with onset at least 14 days after the administration of study-agents, and secondary endpoint was protection of severe or critical COVID-19; 2) Local or systemic adverse events occurred within 28 days after the receipt of study-agent.

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: “Eligible participants were randomly assigned in a 1:1 ratio. Unique allocation numbers were generated by computer and designated to study-agent vials with a block size of eight.”
Comment: Allocation sequence random random. No information on allocation concealment.
Imbalances in baseline characteristics appear to be compatible with chance.
Deviations from intervention
Some concerns 		Quote: “Double-blind”
Comment: Blinded study (participants and personnel/carers)

MORTALITY, LOCAL ADVERSE EVENTS, SYSTEMIC ADVERSE EVENTS, ADVERSE EVENTS, SERIOUS ADVERSE EVENTS
Analysis on those who received at least one dose of the intervention was performed for safety outcomes.
Of note, 1 participant assigned to V-01 received placebo and 1 participant assigned to placebo received V-01. This deviation was balanced and is unlikely to affect the outcome.
As we are assessing the effect of assignment to intervention, the analysis method performed was considered appropriate.
Risk assessed to be low for the outcomes: Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.

CONFIRMED SYMPTOMATIC COVID
Per protocol analysis was performed for Confirmed symptomatic COVID.
Deviations from intended intervention arising because of the study context: 11 vs. 12 did not receive the assigned injection; 5 vs. 0 were PCR positive at baseline; 166 vs. 171 had follow up <15 days; 4 versus 3 were infected within 15 days.
As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately.
Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID.

NEUTRALIZING ANTIBODY ASSAY GMT
Immunogenicity was assessed in a small predefined subgroup.
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 balance between groups.
Risk assessed to be some concerns for the outcomes:Neutralizing antibody GMT.
Missing outcome data
Low 		Comment: 10241 participants randomized; 10218 participants analyzed for safety; 9869 participants analyzed for efficacy; a randomly selected subgroup of 420 participants analyzed for immunogenicity.
Data available for all or nearly all participants randomized for efficacy and safety.
Data not available for all or nearly all participants randomized for immunogenicity.
Evidence that the result is not biased.
Reasons: Immunogenicity was assessed in a small randomly selected subgroup.
Missingness could not depend on the true value of the outcome.
Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Neutralizing antibody GMT. Mortality. Local adverse events. Systemic adverse events. 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: Confirmed symptomatic COVID. Mortality. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective registry was available.
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 outcome: Confirmed symptomatic COVID. Mortality. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Overall risk of bias
Some concerns