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 ?g 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 ?g with Algel-IMDG, 6 ?g with Algel-IMDG, 6 ?g 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 ?g with Algel-IMDG, 6 ?g with Algel-IMDG, 6 ?g 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. |
| Deviations from intervention |
Low |
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. As we are assessing the effect of assignment to intervention, the available case intention-to-treat analysis method performed on these outcomes, was considered appropriate. Risk assessment to be low for the outcomes: 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 assessment to be low for the outcomes: 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 low for the outcomes: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: Two trial registries were available. Serious adverse events was listed as outcome, with timepoints specified in one of the registries. Extracted results were not selected from multiple outcome measurements or analyses of the data. Risk assessed to be low for the outcomes: Serious adverse events. |
| Overall risk of bias |
Low |