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: "Groups were randomly assigned using an interactive response technology system. Block randomisation was used, with blocks of varying sizes, whereby greater numbers of participants were allocated to the two-dose, AS03-adjuvanted groups."
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Some concerns |
Quote: "Only the study site staff who prepared and administered the vaccine knew which vaccine was administered, and they were not involved in assessment of adverse events or of the study data" (pre-print) "Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)" (registry)
Blinded study (participants, personnel, investigators). Study states that all randomized participants who received at least one dose were analyzed for safety outcomes; however, in addition to participants not meeting all inclusion criteria that were excluded before receiving the first dose, two additional participants in the CoV2 preS dTM LD + ASO3 were excluded from analyses. Similarly, two participants were excluded from the CoV2 preS dTM LD + AFO3 and one participant from the CoV2 preS dTM HD + AFO3. Reasons for exclusion from analyses were not clearly reported, although some are described as 'protocol deviations' in the flow chart of the report. Risk assessed to be some concerns for outcomes: Systemic adverse events. Unsolicited adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 271 participants randomized to 2-dose arms; 264 participants analyzed for safety.
Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Systemic adverse events. Unsolicited 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: Systemic adverse events. Unsolicited adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry and protocol were available.
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:Systemic adverse events. Unsolicited adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |