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:"The randomization scheme was generated using SAS software version 9.4 (SAS Institute Inc, USA) for Interactive Response Technology (IRT)
with 1:1 allocation to SII-NVX-CoV2373 or control vaccine within each of the two prime cohorts. The study participants, the study personnel
responsible for the evaluation of any study endpoints and the laboratories involved in the immunogenicity testing were blinded to the
treatment allocation. Personnel involved in getting randomization code by accessing interactive web response system (IWRS) and
administration were unblinded and they did not conduct any study evaluations"
Comment: Allocation sequence random. Unclear allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote: “The study participants, the study personnel
responsible for the evaluation of any study endpoints and the laboratories involved in the immunogenicity testing were blinded to the
treatment allocation. ”
Comment: Blinded study (participants and outcome assessors) NEUTRALIZING ANTIBODY GMT ASSAY Quote: “Per Protocol population consisted of all participants who received the study vaccine, provided an evaluable serum sample post vaccination for at least one assessment, had baseline (day 1) data available, excluding any data from time points following a SARS-CoV-2 infection or major protocol deviation before day 29. All immunogenicity analyses were performed using this population" Per-protocol analysis was performed on the outcomes. Reasons for exclusion: no exclusions due to protocol deviations. As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There were no substantial impact of failure to analyze participants according to their randomized assignment since there were no exclusions. Risk assessed to be low for the outcome: Neutralizing antibody GMT assay. NEUTRALIZING ANTIBODY GMT ASSAY OMICRON. SEROCONVERSION RATE OMICRON Quote: "Immunogenicity against variants of concern was assessed in a randomly selected subset of 46 participants for anti-S IgG against Omicron BA.1" Per-protocol analysis was performed on the outcomes. Reasons for exclusion: outcome assessed in a subset of the participants" As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There were probably no substantial impact of failure to analyze participants according to their randomized assignment since the subset of participant was randomly selected. Risk assessed to be some concerns for the outcome: Neutralizing antibody GMT assay Omicron and Seroconversion rate Omicron ADVERSE EVENTS Quote:"Safety Population included all participants who received the study vaccines." 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 outcome: Adverse events |
| Missing outcome data |
Low |
Comment: 186 participants randomized; 185 participants analyzed for Adverse events and Neutralizing antibody assay GMT; 46 participants analyzed for Neutralizing antibody assay GMT Omiconr and Seroconversion rate Omicron
NEUTRALIZING ANTIBODY ASSAY GMT, ADVERSE EVENTS Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes Neutralizing antibody assay GMT and Adverse events. NEUTRALIZING ANTIBODY ASSAY GMT OMICRON, SEROCONVERSION RATE OMICRON Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons:outcomes assessed in a subset of the population. Risk of bias assessed in domain. Risk assessed to be low for the outcomes Neutralizing antibody assay GMT Omicron and Seroconversion rate 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. Neutralizing antibody GMT Omicron. Seroconvercion rate Omicron. Adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (dated 21/04/2022)
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 some concerns for the outcome: Neutralizing antibody GMT. Neutralizing antibody GMT Omicron. Seroconversion rate Omicron. Adverse events. |
| Overall risk of bias |
Some concerns |