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: "Participants in DMID 21-0002 were randomized 1:1 to receive a third mRNA vaccination in the Monovalent variant or Bivalent groups."
Comment: Allocation sequence probably random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote:"Open Label"
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Hence, deviations did not arise because of the trial context. SYSTEMIC ADVERSE EVENTS, ADVERSE EVENTS, SERIOUS ADVERSE EVENTS ITT analysis with N randomized denominators for 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 for the outcomes: Systemic adverse events. Adverse events. Serious adverse events >br/> SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT Per-protocol analysis was performed on the immunogenicity outcomes. Reasons for exclusion: testing was restricted to the participants in the monovalent prototype group (100mg) received a 25 or 50 mcg primary series. Detectable titers were not observed in all participants. 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 following the pre-determined protocol. Risk assessed to be some concerns for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. |
| Missing outcome data |
Low |
Comment:96 participants randomized; 96 participants analyzed for safety; 88 participants analyzed for immunogenicity.
SYSTEMIC ADVERSE EVENTS, ADVERSE EVENTS, SERIOUS ADVERSE EVENTS Data available for all or nearly all participants randomized for safety. Risk assessed to be low for the outcomes: Systemic adverse events. Adverse events. Serious Adverse events SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT Data not available for all or nearly all participants randomized for immunogenicity No evidence that the result is not biased. Reasons: Addressed in ROB2 Missingness could not depend on the true value of the outcome. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. |
| 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. Unblinded study (outcome assessor) SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. SYSTEMIC, ADVERSE EVENTS,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: Adverse events. Systemic Adverse Events.Serious adverse events |
| Selection of the reported results |
Low |
Comment: The prospective registry (Date February 25th 2020) was used for data extraction and analysis.
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: Specific antibody GMT. Neutralizing antibody GMT. Systemic adverse events. Adverse events. Serious Adverse events |
| Overall risk of bias |
Some concerns |