Trial RPCEC00000338
Publication Pérez-Rodríguez S, Vaccine, 2022
Primary outcome on the report: The two co-primary outcomes, safety and reactogenicity, were assessed until 28 days after the third, last dose. Safety was measured by the occurrence of serious adverse events. Results of laboratory analyses on blood samples at 28 days after the last dose were compared to pre-vaccination values.

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
Low 		Quote: “Allocation of participants in each vaccine group was done by simple random blinded sampling using a centralized technology. Each participant got an identification code, which matched the vaccine vial label code.”
Comment: Allocation sequence random. Allocation sequence concealed.
Risk assessed to be low.
Deviations from intervention
Low 		Quote: “All study staff, investigators, sponsor personnel and subjects, remained blinded until the conclusion of the study (28 days after the last dose of the vaccine was applied to all volunteers).”
Comment: Blinded study (participants and personnel/carers)
All randomized subjects were included in the safety analysis.
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.
Per-protocol analysis was performed on the immunogenicity outcomes.
Reasons for exclusion: positive COIVD-19 infection (0 vs 1 vs 0)
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 small number of exclusions.
Risk assessed to be low for the outcome: Neutralizing antibody GMT.
Missing outcome data
Low 		Comment: 60 participants randomized; 60 participants analyzed for safety/57 participants analyzed for immunogenicity.
Data available for nearly all participants randomized.
Risk assessed to be low for the outcomes: Neutralizing antibody GMT. 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: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective trial registry was available (10 October, 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: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Overall risk of bias
Low