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 |
|
Quote: "Randomization was stratified according to trial center and age (18 to 59 years or ≥60 years) and was performed with the use of an interactive Web-response system.â€
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
"Quote: ""all participants and study personnel, with the exception of those preparing or administering the injections, were unaware of group assignments"" Comment: Blinded study (participants and personnel/carers). Per-protocol analysis was performed on efficacy outcomes. Reasons for exclusion: 14 [0.9%] vs. 10 [1.3%] did not receive 2 doses; 64 [4.2%] vs. 11 [1.5%] had important protocol deviations as determined by the investigator or did not complete 1 month follow-up after the second dose. For immunogenicity, a subset of 394/2285 (117.2%) was analysed as planned in the protocol. As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There was probably no substantial impact of failure to analyze participants according to their randomized assignment due to the small number of excluded participants for efficacy and to the pre-planned method of analysis for immunogenicity. Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID. |
| Missing outcome data |
Low |
"Comment: 2285 participants randomized; 2268 to 2260 participants analyzed for safety; 2186 participants analysed for efficacy; 394 participants analysed for immunogenicity. Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. |
| 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: Confirmed symptomatic COVID. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, registry were available (dated 25 March 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: Confirmed symptomatic COVID. |
| Overall risk of bias |
Some concerns |