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: “All eligible participants were 1:1 randomly assigned to receive a single dose of either the same vaccine as their prime dose ChAdOx1 (homologous group) or the Medigen COVID-19 vaccine MVC-COV1901 (heterologous group). Stratified randomization was used based on the intervals between prime and boost vaccination. Participants were stratified according to the prime-boost intervals of 4–6 weeks and 8–10 weeks, respectively, with equal-sized strata. Randomization was applied to each stratum and the random number list was generated by an independent study statistician using SAS software.”
Comment: Allocation sequence random. No information on allocation concealment. |
| Deviations from intervention |
Low |
Quote: “The treatment phase was conducted in a single-blinded fashion such that the participants were masked to the vaccine received but not to the prime-boost interval. Clinical staffs who involved in the vaccine delivery were aware of which vaccine the participant received, but the participant remained blinded by preparing the vaccine out of sight and applying a masking tape over the vaccine syringe. Laboratory staffs were also blinded to the vaccine the participant received, which may minimize the evaluation bias from the knowledge about the treatment assignment of the participant.”
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. ITT analysis (with N randomized denominators) performed for all 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: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 100 participants randomized; 100 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Withdrawals due to 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. Single-blinded study (participants) MORTALITY, SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. LOCAL and SYSTEMIC ADVERSE EVENTS Participants were blinded to assignment and self-report occurrence and severity of reactogenicity events. Risk assessed to be low for the outcomes: Local adverse events. 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: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective protocol, statistical analysis plan, registry were available (dated September 23, 2021).
Outcomes 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. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |