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: “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.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: Double-blind. “The statisticians who conducted randomization were not involved in other work relevant to this clinical trial. The trial participants, field investigators, and nurses who administrated the vaccine or placebo were unaware of the trial-group assignments during the trial.”
Comment: Blinded study (participants and personnel/carers) Safety analysis on those who received at least one dose of the intervention and vaccine efficacy included all the participants who had undergone randomization, were not from China, and received at least one dose of vaccine or placebo. 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: Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. Efficacy anlaysis on those who had undergone randomization and completed the three-dose regimen. Reasons for exclusion: received another vaccine (31 vs 30), protocol violations (3 vs 2), had confirmed covided between dose 1 and 7 days after dose 3( 27 VS 46). As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. Probably no substantial impact of failure to analyze participants according to their randomized assignment due to balance between groups. Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. |
| Missing outcome data |
Low |
Comment: 28904 participants randomized; 25193 participants analyzed for efficacy; 28873 participants analyzed for safety.
Data available for all or nearly all participants randomized for safety. Data not available for all or nearly all participants randomized for efficacy. Reasons: per-protocol analysis. This potential source of bias has been taken into account in domain 2. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. Mortality. 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: Confirmed symptomatic COVID. Confirmed severe COVID. Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol (25 Oct 2020), statistical analysis plan (2 Aug 2021) and registry (30 Nov 2020) were available.
Outcomes pre-specified in registry, protocol and/or statistical analysis plan. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |