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: "The master randomisation list was uploaded on 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 would set the randomisation number and the allotment of the kit without displaying the true group allocation, and the system would allocate the same treatment group for the second visit. For the first 50 participants, a block size of five with ten blocks was generated for the 3 mcg with Algel-IMDG and control groups at a ratio of 4:1. In the remaining participants, the number of blocks was 20. For the first 15 blocks, a block size of 16 was used to randomly assign participants (3:5:5:3) to 3 mcg with Algel-IMDG, 6 mcg with Algel-IMDG, 6 mcg with Algel, or Algel-only control. The next five blocks were size 17, and used to randomly assign participants (3:5:5:4) to 3 mcg with Algel-IMDG, 6 mcg with Algel-IMDG, 6 mcg with Algel, or Algel-only control. An unmasked contract research organisation, Sclin Soft Technologies, generated the randomisation list for the study." Comment: Allocation sequence random. Allocation sequence concealed. Risk assessed to be low. |
| Deviations from intervention |
Some concerns |
Quote: "The appearance, color, and viscosity were identical across all treatment and control formulations. Participants, investigators, study coordinators, study-related personnel, and the sponsor were blinded to the treatment group allocation (excluding an unblinded CRO, who was tasked with the dispatch and labeling of vaccine vials and the generation of the master randomization code). Blinding was maintained using the randomization code."
Comment: Blinded study (patients, personnel, and investigtors). No participant cross-over. Per-protocol analysis was performed on the outcomes. Reasons for exclusion: protocol deviation (1), positive for SARS-CoV-2 (1) 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 number of exclusions Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. Specific antibody GMT. Local adverse events. Systemic adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: Data from interim analysis. 375 participants randomized, 365 participants analyzed. Data available for all or nearly all participants. Reasons for missing data were withdrew consent (n=4), protocol deviation (n=1), virological COVID-19 (n=1), and discontinued (n=4). Reasons for missing data not likely related to outcome. Risk assessed to be low for the outcomes: Neutralizing antibody GMT. Specific antibody GMT. Local adverse events. Systemic adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Probably appropriate method of measuring the outcome. Measurement or ascertainment of outcome probably not differ between groups. Comment: Blinded study (outcome assessor). Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. Specific antibody GMT. Local adverse events. Systemic adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The prospective registry was available (July 15, 2020).
Serious adverse events and Neutralizing antibody GMT were pre-specified Outcomes pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Risk assessed to be low for the outcomes: Serious adverse events. Neutralizing antibody GMT Local adverse events, Systemic adverse events and Specific antibody GMT were not mentioned in the registry. Outcome not pre-specified No information on whether the results were selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes:Local adverse events. Systemic adverse events. Specific antibody GMT |
| Overall risk of bias |
Some concerns |