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|
|Quote: “Participants were assigned to study groups in a 1:1:1:1 fashion; randomization was stratified by study site after obtaining written informed consent.”
Comment: Allocation sequence probably random. No information on allocation concealment.
Imbalances in baseline characteristics appear to be compatible with chance.
Risk assessed as some concerns
|Deviations from intervention||
|Quote: “single-(participant)-blinded Participants were unblinded for the booster vaccination by e-mail eight days after injection, after completing the reactogenicity questionnaires.”
Comment: Blinded study (participants)
Deviations from intended intervention arising because of the study context:
No participant cross-over.
Per-protocol analysis was performed on the outcomes.
Reasons for exclusion: baseline positive (2.6%, 1.7%, 0.9%, 1.7%), positive between baseline and follow up (1.8%, 0.9%, 0.0%, 0,0%).
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 balance between groups.
Risk assessed to be some concerns for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Local adverse events. Systemic adverse events.Serious adverse events.
|Missing outcome data||
|Comment: 461 participants randomized; 182 participants analyzed for neutralizing antibody GMT and cellular response; 433 participants analyzed for reactogenicity and serious adverse events specific antibody GMT.
Data not available for all or nearly all participants randomized.
No evidence that the result is not biased.
Reasons for missigness for the outcomes reactogenicity and specific antibody GMT are related to prtocol deviation and this bias was addressed in domain 2.
Risk assessed to be low for the outcomes: Specific antibody GMT. Local adverse events. Systemic adverse events. Serious adverse events
Reasons (neutralizing antibody GMT and cellular response): Only measured in a subset of participants.
Missingness could depend on the true value of the outcome.
Not likely that missingness depended on the true value of the outcome because there is no major imbalance between groups.
Risk assessed to be some concerns for the outcomes: Cellular response. Neutralizing antibody GMT
|Measurement of the outcome||
|Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT, CELLULAR RESPONSE
Observer-reported outcome not involving judgement.
Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response.
LOCAL, SYSTEMIC, and SERIOUS ADVERSE EVENTS
Blinded study (patient who is the outcome assessor).
Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events.Serious adverse events.
|Selection of the reported results||
|Comment: The protocol, statistical analysis plan, supplementary materials and registry (dated June 16, 2021) were available.
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.Cellular response. Local adverse events. Systemic adverse events.Serious adverse events.
|Overall risk of bias||