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 |
Some concerns |
Quote: "Participants were randomly assigned to 1 of the 2 vaccine groups or a control group
receiving aluminum hydroxide (alum) adjuvant only (in a 1:1:1 ratio), according to unique
serial numbers generated by an independent statistician. The concealed random grouping
allocation and blind codes were blinded to the investigators, participants, and statisticians."
Comment: Allocation sequence random Unclear allocation concealment. Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: “ The concealed random grouping allocation and blind codes were blinded to the investigators, participants, and statisticians.The masking was removed in the event of a medical emergency requiring acute intervention,upon the responsible investigator’s approval and the data and safety monitoring board’s
knowledge. ”
Comment: Blinded study (participants and personnel/carers) CONFIRMED SYMPTOMATIC COVID, CONFIRMED SEVERE COVID Analysis was performed in the modified full analysis set that included all subjects who received the booster dose of vaccination except: Subjects did not enter the case surveillance period whose vaccine shed within 14 days after booster dose;less than 14 days after the booster dose to the cut-off date of data analysis; PCR-positive subjects within 14 days of booster dose; Subjects diagnosed with COVID-19 within 14 days of booster dose; Received other COVID-19 vaccines within 14 days of booster dose; PCR positive at the screening period. 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 balance of exclusions between arms. Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. NEUTRALIZING ANTIBODIES ASSAY GMT Outcome was assessed on a subset of participants. Quote "The first 150 serum samples (numbers B00001-2 to B00164-2) of the immunogenic subgroups were sequentially selected according to the serum number for the cross-neutralization analysis of ancestral strains (10 in total) in different regions and another 150 samples (No. B00165-2 to B00338-2) for cross-neutralization analysis of variant strains. 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 balance of exclusions between arms. Risk assessed to be some concerns for the outcome: Neutralizing antibodies assay GMT ADVERSE EVENTS. SERIOUS ADVERSE EVENTS Analysis included all subjects who received the booster dose of vaccine. 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:Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 9370 participants randomized; 9071 participants analyzed for efficacy outcomes; 150 participants analyzed for inmunogenicity outcomes; 9309 participants analyzed for safe outcomes.
EFFICACY AND SAFETY OUTCOMES Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. Adverse events. Serious adverse events. NEUTRALIZING ANTIBODIES ASSAY GMT Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: Outcome was assessed in a sub-set of pariticipants as pre-specified. Risk of bias assessed in domain 2. Risk assessed to be low for the outcome: Neutralizing antibody assay GMT. |
| 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. Neutralizing antibody assay GMT. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospecitve registry was available (dated January 22, 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 outcome: Confirmed symptomatic COVID. Confirmed severe COVID. Neutralizing antibody GMT. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |