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 stratified into two age groups (18–55 or 56–85 years) and randomized 3:1 to receive two doses of BNT162b2 (COMIRNATY®, Pfizer-BioNTech8 ) 30 μg or saline placebo by intramuscular injection, 21 days apart. An independent randomization professional generated a participant randomization table and performed a block randomization, assigning participants using an interactive response technology system.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Double-blind, placebo-controlled trial.” “Study participants, study personally at each clinical site, investigators, trial statisticians and the sponsor’s management team were blinded to treatment assignment.”
Comment: Blinded study (participants and personnel/carers). Safety and immunogenicity analysis conducted on those who received at least one dose of the intervention. As we are assessing the effect of assignment to intervention, the analysis method performed on these outcomes, was considered appropriate. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 960 participants randomized; 959 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. 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: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry and protocol were available (Date December 2,2022).
Outcome 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: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Low |