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 |
Quotes: "An independent statistician used SAS statistical software version 9.4 (SAS Institute Inc., San Diego, CA, USA) to generate a random table, from which random numbers were assigned to eligible participants by investigators, and investigational vaccines and placebos were allocated serial numbers" "Statisticians were not allowed to disclose the masking code to any personnel in the clinical trials"
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "all the participants, investigators, and laboratory staff remained blinded unless formal or emergency unblinding was required"
Comment: Blinded study (participants and personnel/carers). Intention-to-treat analysis. 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: Local adverse events. Systemic adverse events. Adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 880 participants randomized; 880 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Adverse events. Withdrawals due to 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: Local adverse events. Systemic adverse events. Adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The trial registry was available (dated 7 April 2021).
Outcomes not pre-specified in detail (just “Safety outcomes”). No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Local adverse events. Systemic adverse events. Adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |