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: "Block-randomized in a 1:1 ratio based on the presence or absence of peripheral B lymphocytes by a computerized randomization algorithm"
Comment: Allocation sequence random. No information on allocation concealment.
|Deviations from intervention||
|Quote: "All patients were blinded throughout visit four, mainly to allow objectivity in safety assessment of the two strategies; blinding of vaccines was ensured by using prearranged dose aliquots in syringes without reference to the type used."
Comment: Single blinded study (participants).
Deviations from intended intervention arising because of the study context:
No participant cross-over.
Hence, deviations did not arise because of the trial context.
Data for the outcome were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention.
Risk assessed to be low for the outcomes: Cellular response. Local adverse events. Withdrawals due to adverse events.
|Missing outcome data||
|Comment: 60 participants randomized; 55 participants analyzed for adverse events; 36 articipants analyzed for cellular response.
Data not available for all or nearly all participants randomized.
No evidence that the result is not biased.
Reasons: withdrew informed consent (2 vs. 2), had viral infection at vaccination date (1 vs. 0); for cellular response: matched samples before and after the third vaccination were unavailable (8 vs. 11).
Missingness could depend on the true value of the outcome.
Not likely that missingness depended on the true value of the outcome.
Risk assessed to be some concerns for the outcomes: Cellular response. Local adverse events. Withdrawals due to adverse events.
|Measurement of the outcome||
|Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Laboratory- and participant-blinded study.
Cellular response is a laboratory, observer-reported outcome not involving judgement.
Risk assessed to be low for the outcome: Cellular response.
The authors reported on adverse events that contained both investigator-reported (unclear blinding) and self-reported (blinded) 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: Local adverse events. Withdrawals due to adverse events.
|Selection of the reported results||
|Comment: The protocol, statistical analysis plan, and prospective registry were available.
Cellular response was listed as an outcome.
Results were probably not selected from multiple outcome measurements or analyses of the data.
Risk assessed as low for the outcome: Cellular response.
Local pain at the injection site was used as a proxy outcome for Local adverse events and were not listed in the registry, nor were withdrawals due to adverse events.
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 as some concerns for the outcomes: Local adverse events. Withdrawals due to adverse events.
|Overall risk of bias||