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: "Participants were assigned a computer-generated randomisation code" "The master randomisation list was uploaded to the Interactive Web Response System, which contained the randomisation number and intended allocation. The depot manager uploaded the kit code list and assigned the kits to the sites that had the kit codes and the allocation groups. At the site level, the system set the randomisation number and the allotment of the kit without displaying the true group allocation, and the system allocated the same treatment arm for the second visit. A block size of four was utilised. An unblinded Contract Research Organization (CRO), Sclin Soft Technologies, was involved in randomisation for the study." Comment: Allocation sequence random. Allocation concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "The appearance, color, and viscosity were identical across all formulations." Quote: "Participants, investigators, study coordinators, study-related personnel, and the sponsor were blinded to the treatment group allocation". Quote: "The blinded study nurse was responsible for vaccine preparation and administration. Each vial contained a unique code that ensured appropriate blinding." Comment: Blinded study (patients, nurses, physicians, and investigators). No participant cross-over. Data were analyzed using intention-to-treat analysis. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: Data from interim analysis. 380 patients randomized; 380 patients analyzed for local and systemic adverse events. Data available for all or nearly all participants. Risk assessed to be low for the outcome: Local adverse events. Systemic adverse events. The number of participants analyzed for Serious adverse events on day 118 is not reported. Risk assessed to be some conserns for the outcome: serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Blinded study (outcome assessor). Risk assessed to be low for the outcome: Local adverse events. Systemic adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective trial registry and protocol were available. Serious adverse events was listed as outcome with timepoints specified in one of the registries (CTRI, but not NCT). Local and systemic adverse events were listed only in the protocol 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: Local adverse events. Systemic adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |