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: "Randomization of the AZ/AZ and the AZ/BNT arms was performed in a 1:1 ratio stratified by study site (Innsbruck/Kufstein/Schwaz) and sex (male/female). Randomization code has been generated by the study statistician using permutated blocks using Stata/MP 16.1. Randomization lists were provided by the statistician to the study monitor who performed randomization of participants after verification of inclusion and exclusion criteria as well as stratification status and after screening assessments have been performed."
Comment: Allocation sequence random No information on allocation concealment |
| Deviations from intervention |
Some concerns |
Quote:"Single blinding. Study participants of the AZ/AZ and the AZ/BNT arms were blinded regarding the type of second vaccination for 90 days following second vaccination."
Comment: Blinded 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. Per-protocol analysis was performed on the outcomes. Reasons for exclusion: 3 vs 7 did not receive the vaccination, 5 vs 7 had not yet reached the 30 day follow up at the time of the interim analysis or were not available and followed up at the next visit. Others missing due to drop out are addressed in ROB3. 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 numbers. Risk assessed to be some concerns for the outcomes: Cellular response. Local adverse events. Systemic adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 234 participants randomized; 222 participants analyzed for safety; 212 participants analyzed for immunogenicity.
Data available for all or nearly all participants randomized as other missing data addressed in ROB3. Only 1 vs 1 dropped out after the vaccination. Risk assessed to be low for the outcomes: Cellular response. Local adverse events. Systemic adverse events. Serious adverse events. |
| 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) CELLULAR RESPONSE Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Cellular response. LOCAL, SYSTEMIC, and 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: Local adverse events. Systemic adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and registry were available
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: Cellular response. Local adverse events. Systemic adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |