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: “Patients were randomized 1:1 to receive a third dose of the same, previously administered, mRNA vaccine (mRNA-1273 or BNT162b2) or a single dose of the vector vaccine (Ad26COVS1). Randomization was stratified by maintenance immunosuppressive regimen calcineurin inhibitor (CNI) vs co-stimulation blockade (belatacept). To ensure that comparison groups were approximately the same size, we applied block randomization with a block size of 4 to balance participants randomized to each group.”
Comment: Allocation sequence random. No information on allocation concealment. |
| Deviations from intervention |
Low |
Quote: “Single-blind”
Comment: Partially 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. Outcomes were assessed using intention-to-treat analysis of available cases. As we are assessing the effect of assignment to intervention, the analysis method performed was considered appropriate. Risk assessed to be low for the outcomes: Mortality. Cellular response. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 201 participants randomized; 198 participants analyzed for mortality and safety; 197 participants analyzed for immunogenicity.
Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality. Cellular response. 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) MORTALITY, CELLULAR RESPONSE Observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Cellular response. SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious 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 |
Low |
Comment: The protocol, statistical analysis plan, registry (dated 31 May 2021) were available.
Outcomes were 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 outcomes: Mortality. Cellular response. Serious adverse events. |
| Overall risk of bias |
Some concerns |