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: "A non-blind study team member (pharmacist, nurse, etc.) will be responsible for the assignment and preparation of the investigational product to the volunteer in the study. The non-blind study team member will draw the product on the arm assigned to the volunteer into a standard type syringe determined by the research team and label the subject number, subject initials, Omega Research Randomization and Investigational Product Management System (Omega Interactive Voice Response Systems [IVRS]/Interactive Web Response Systems [IWRS]) code and preparation time and date. Thus, the investigational product, which has been made suitable for blind administration, will be administered to the volunteers by the study nurse. Except for the study team member who was not blinded within the scope of the study, the study team, including the study nurse, and the volunteers will remain blind."
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Low |
Quote: “Except the study pharmacist preparing the application product, the study team and volunteers, including the nurse who performed the vaccination, were blinded.”
Comment: Blinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: No participant cross-over. Safety analysis was conducted on those who received at least one dose of the intervention. 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. Immunogenicity analysis was performed on all participants who completed follow up. Reasons for exclusion: 4/108 in the TURKOVAC arm discontinued due to reasons “not related to the vaccine”. 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 small numbers and discontinuation being unrelated to the vaccine. Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. |
| Missing outcome data |
Low |
Comment: 222 participants randomized; 222 participants analyzed for safety; 218 participants analyzed for immunogenicity.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. 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, Adverse events, and Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and registry were available (dated July 28, 2021).
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 outcomes: Neutralizing antibody GMT, Adverse events, and Serious adverse events. |
| Overall risk of bias |
Some concerns |