| Bias | Author's judgement | Support for judgement |
| Randomization |
Some concern |
Quote: "Participants were assigned a computer-generated randomization number" "an unblinded CRO, who was tasked with the dispatch and labeling of vaccine vials and the generation of the master randomization code" Comment: Allocation sequence random. Allocation sequence concealed. Any potential imbalances in baseline characteristics could not be assessed because the supplementary appendix was not accessible at the time of data extraction. |
| Deviations from intervention |
Low |
Quote: "The appearance, color, and viscosity were identical across all treatment and control formulations. Participants, investigators, study coordinators, study-related personnel, and the sponsor were blinded to the treatment group allocation (excluding an unblinded CRO, who was tasked with the dispatch and labeling of vaccine vials and the generation of the master randomization code). Blinding was maintained using the randomization code." Comment: Blinded study (patients, personnel, and investigtors). No participant cross-over. As we are assessing the effect of assignment to intervention, the available case intention-to-treat analysis method performed on these outcomes, was considered appropriate. Risk assessed to be low for all outcomes. |
| Missing outcome data |
Low |
Comment: Data from interim analysis. 375 participants randomized, 365 participants analyzed. Data available for >95% of population. Reasons for missing data were withdrew consent (n=4), protocol deviation (n=1), virological COVID-19 (n=1), and discontinued (n=4). Reasons for missing data not likely related to outcome. Risk assessment to be low for the outcomes: Confirmed symptomatic COVID. Hospitalization or death due to COVID. Neutralizing antibody seroconversion. Neutralizing antibody GMTs. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Hospitalization or death due to COVID. Neutralizing antibody seroconversion. Neutralizing antibody GMTs. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: Two trial registries were available. Adverse events, serious adverse events, and neutralization antibody titres were listed as outcomes, with timepoints specified in one of the registries. Extracted results were not selected from multiple outcome measurements or analyses of the data. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Hospitalization or death due to COVID. Neutralizing antibody seroconversion. Neutralizing antibody GMTs. Serious adverse events. |
| Overall risk of bias |
Some concerns |