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: "Participants were randomized 1:1 by an interactive web-based system."
Allocation sequence random.Allocation sequence concealed Risk assessed to be low. |
Deviations from intervention |
Some concerns |
Quote: “observer blinded”
Comment: Blinded study (participants and personnel/carers) SAFETY Data were analyzed using intention-to-treat analysis for the safety outcomes. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed as low for the outcomes: Severe COVID. Adverse events. Serious adverse events EFFICACY Data were analyzed using intention-to-treat analysis for the outcomes: Mortality. Severe COVID This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed as low for the outcomes: Mortality. Severe COVID Per-protocol analysis was performed on the outcomes: Confirmed symptomatic COVID. Reasons for exclusion: Positive at baseline (689 Vs 716) not received 2 vaccinations as randomized (326 Vs 430) Reasons foe exclusion in the 12-15 yo group not reported As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. Risk assessed as some concerns for the outcome: Confirmed symptomatic COVID. |
Missing outcome data |
Low |
Comment: 46429 participants randomized (44165 participants aged ≥16 years randomized; 2264 participants aged 12-15 years randomized, previously reported, Frenck 2021) / 42094 participants aged ≥12 years analyzed for Confirmed symptomatic COVID / 46077 participants aged ≥12 years analyzed for Confirmed COVID severe or critical / 43847 participants aged ≥16 years analyzed for safety outcomes.
Data available for nearly all participants. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed COVID severe or critical. Adverse events. Serious adverse events. Mortality |
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. Severe COVID. Mortality. Adverse events. Serious adverse events. |
Selection of the reported results |
Low |
The propective registry is available (April 30, 2020)protocol and statistical plan are 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: Confirmed symptomatic COVID. Severe COVID. Mortality. Adverse events. Serious adverse events. |
Overall risk of bias |
Some concerns |