Trial NCT05293548
Publication Al Kaabi N, Signal Transduct Ther, 2023
Primary outcome on the report: The immunogenicity and safety of the booster vaccination of NVSI-06-09 against SARS-CoV-2 Omicron variant, in comparison with the boost of BBIBP-CorV, on day 14 after the vaccination. The immunogenicity was evaluated by the geometric mean titers (GMTs) of anti-Omicron neutralizing antibodies (nAbs), and the four-fold rise rate of the neutralizing GMTs from baseline. Anti-Omicron nAb titers were measured by live-virus microneutralization assays. The safety was assessed by occurrence and severity of adverse reactions.

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: "For participant allocation, eligible persons were assigned to two booster groups using a stratified blocked randomization method by SAS 9.4 software, in which stratification was based on different doses (two or three doses) of BBIBP-CorV that they received prior to enrollment and the block size was set to 4. The vaccine randomization list was also generated by SAS 9.4 software using the block randomization method with a block size of 4. Both participant and vaccine randomization lists were generated by an unblinded statistician, and then imported into the Interactive Web Response System (IWRS). After enrollment, each participant was assigned a randomization number from IWRS. At the clinical site, a vaccine number was also obtained from IWRS for vaccination accordingly."
Comment: Allocation sequence random
Allocation sequence concealed
Imbalances in baseline characteristics appear to be compatible with chance
Deviations from intervention
Some concerns 		Quote: "Participants and clinical operation team involved in safety data collection and immunogenicity assessments were blind to treatment allocation during the trial. Vaccine preparation was done by independent personnel to ensure identical appearance between the studied and control vaccines. Individuals involved in randomization"
Comment: Blinded study (participants and personnel/carers)

LOCAL ADVERSE EVENTS, SYSTEMIC ADVERSE EVENTS, ADVERSE EVENTS, SERIOUS ADVERSE EVENTS
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: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.

NEUTRALIZING ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT OMICRON
Per-protocol analysis was performed on the immunogenicity outcomes.
Reasons for exclusion: 2/260 vs 4/256 blood samples were not collected on D14 after booster vaccination; 0 vs 2 blood samples collected over the predefined time window; 3 vs 1 met exclusion criteria.
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 the small numbers.
Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. Neutralizing antibody GMT Omicron.
Missing outcome data
Low 		Comment: 516 participants randomized; 516 participants analyzed for mortality and safety outcomes; 504 participants analyzed for immunogenicity.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Neutralizing antibody GMT Omicron. 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: Neutralizing antibody GMT. Neutralizing antibody GMT Omicron. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective protocol (Date 1st April 2022) , statistical analysis plan and registry (Date 24th March 2022) were available.
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: Neutralizing antibody GMT. Neutralizing antibody GMT Omicron. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events.
Overall risk of bias
Some concerns