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 participants were randomized to 1 of the 4 vaccination
groups"
Comment: Allocation probably random. Allocation Unclear allocation concealment. Stop here for studies with <300 participants. For studies with sample size around 300 and above: Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: “Open label”
Deviations from intended intervention arising because of the study context: No participant cross-over. Hence, deviations did not arise because of the trial context. SERIOUS ADVERSE EVENTS Intention to treat analysis performed in the 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: Serious adverse events. NEUTRALIZING ANTIBODY ASSAY GMT. SEROCONVERSION OMICRON.NEUTRALIZING ANTIBODY ASSAY GMT OMICRON. Per-protocol analysis was performed on the outcomes. Reasons for exclusion: lost to follow up (ID mRNA-1273 0 vs IM mRNA-1273 0 vs ID BNT162b2 2 vs IM BNT162b2 0), Excluded due to COVID-19 (ID mRNA-1273 0 vs IM mRNA-1273 0 vs ID BNT162b2 0 vs IM BNT162b2 2. 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 some concerns for the outcomes: Neutralizing antibody assay GMT. Seroconversion Omicron. Neutralizing antibody assay GMT Omicron. |
| Missing outcome data |
Low |
Comment: 210 participants randomized; 210 participants analyzed for safety; 206 participants analyzed for inmunogenicity.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Serious adverse events, Neutralizing antibody assay GMT. Seroconversion Omicron. Neutralizing antibody assay GMT Omicron. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. NEUTRALIZING ANTIBODY GMT; NAB SEROCONVERSION RATE OMICRON; NEUTRALIZING ANTIBODY GMT (OMICRON ANTIGEN) Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Neutralizing antibody GMT; nAb Seroconversion rate Omicron; Neutralizing antibody GMT (Omicron antigen) SERIOUS ADVERSE EVENTS The authors reported on adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Serious adverse events |
| Selection of the reported results |
Some concerns |
Comment: The protocol, statistical analysis plan were not available and the registry was retrospective (dated 08 January 2022).
No information on whether the result was selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Neutralizing antibody assay GMT. Seroconversion Omicron. Neutralizing antibody assay GMT Omicron. Serious adverse events. |
| Overall risk of bias |
Some concerns |