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 |
Low |
Quote: “An unblinded statistician created the computer-generated randomisation list. Randomisation schedules were prepared separately for participants primed with ChAd/ChAd and BNT/BNT and stratified by study site, age (<70 years and ≥70 years) and subgroup (general and immunology). Permuted random blocks were used, and participants were randomly assigned to the study groups with equal probability within groups A–C. Randomisation was done in the electronic data capture system REDCap, version 10.6.13.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: “Participants, laboratory staff, and the clinical study team not delivering the vaccines were blind to treatment allocation, including those undertaking adverse event assessments. Participant blinding to vaccines was maintained by concealing randomisation pages, preparing vaccines out of sight, and applying masking tape to vaccine syringes to conceal dose, volume, and appearance. The analysing statisticians remained blind until the statistical analysis plan was signed off.”
Comment: Blinded study (participants and personnel/carers) ADVERSE EVENTS, SERIOUS ADVERSE EVENTS ITT analysis was performed in these ourcomes 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: Adverse events, Serious adverse events SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY ASSAY GMT Per-protocol analysis was performed on the immunogenicity outcomes (predefined). Reasons for exclusion: booster vaccine not received, previous COVID-19 at baseline, infection within 14 days of booster, withdrawal before day 28, failed bleed at day 28. Risk assessed to be low for the outcomes: Confirmed severe COVID. Adverse events. Serious adverse events. Risk assessed to be some concerns for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. |
| Missing outcome data |
Low |
Comment: 2883 participants randomized; 2878 participants analyzed for safety; 2557 participants analyzed for immunogenicity.
Data available for nearly all participants randomized for safety. Data not available for all or nearly all participants randomized for immunogenicity. No evidence that the result is not biased. Reasons: Per-protocol analysis was performed on the immunogenicity outcomes (predefined). This potential risk of bias has been taken into account in domain 2. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and prospective registry were available.
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: Specific antibody GMT. Neutralizing antibody GMT. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |