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: “Eligible participants were grouped into three groups, i.e., 1-3 months group, 4-6 months group and ≥6 months group, according to the time interval between their study day 0 and prior vaccination date of the second dose of BBIBP-CorV. For each group, a random table was generated by block randomization method using SAS software (version 9·4). Each enrolled participant was randomly assigned to a code and to receive either a heterologous booster dose of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The trial is double-blind to avoid introducing bias by having randomization and masking process handled by independent personnel from trial operation.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
Deviations from intervention |
Some concerns |
Quote: “Participants, investigators and other staffs remained blinded to individual treatment assignment during the trial.”
Comment: Blinded study (participants and personnel/carers) Planned per-protocol analysis was performed on the immunogenicity outcomes. Reasons for exclusion: no serum collected, ineligibility, wrong vaccine received. 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 between arms. Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT and Neutralizing antibody GMT Omicron |
Missing outcome data |
Some concerns |
Comment: 1800 participants randomized; 1298 participants analyzed for immunogenicity.
Data not available for all or nearly all participants randomized for immunogenicity. Participants were excluded, mainly, because no serum was collectedin 1-3 months and 4-6 months boosting-interval arms. Serum samples of 192 participants with sequential enrollment numbers in ≥6-month boosting-interval group were used to evaluate the neutralizing sensitivities to the Omicron variant. No evidence that the result is not biased. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT and Neutralizing antibody GMT Omicron |
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: Neutralizing antibody GMT and Neutralizing antibody GMT Omicron. |
Selection of the reported results |
Low |
Comment: The prospective registry was available (dated 5 September, 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: Neutralizing antibody GMT and Neutralizing antibody GMT Omicron. |
Overall risk of bias |
Some concerns |