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: "As a safety measure, 6 participants were initially randomly assigned in a 1:1 ratio to the 5-μg and 25-μg rSARS-CoV-2 plus Matrix-M1 groups (groups C and D), vaccinated in an open-label manner, and observed for reactogenicity for 48 hours. Thereafter, the remaining 125 participants were randomly assigned, in a 1:1:1:1:1 ratio and in a blinded manner to one of five vaccine groups according to pregenerated randomization sched-ules, without stratification". Comment: Allocation sequence probably random No information on allocation concealment Risk assessed to be some concerns |
| Deviations from intervention |
Low |
Quote: "This is an observer-blinded study. To maintain the blind, placebo vaccination via IM route
will be included, and unblinded site personnel will manage vaccine logistic, preparation, and
administration (if necessary) so as to maintain the blind from the remainder of the site
personnel and subjects. The unblinded site personnel will not be involved in study-related
assessments or have subject contact for data collection following study vaccine
administration."
Comment: Double blind study.
The primary safety and immunogenicity analyses were conducted after all participants had been followed through day 35. Per-protocol analysis was performed on the outcomes. There were no exclusions due to protocol violations. We considered that the data were analyzed appropriately. Reasons for participants not in the analyses will be assessed in domain 3. Risk assessed to be low for outcomes: Adverse events. Serious adverse events.Specific Ab GMT. Neutralizing Ab GMT |
| Missing outcome data |
Low |
Comment: 54 randomized/51 analyzed for safety outcomes/50 analyzed for immunogenicity outcomes
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: specific antibodies GMT, neutralizing antibodies 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: Specific antibodies GMT. Neutralizing antibodies GMT. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective protocol and statistical analysis plan were available (18 April 2020)
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: Specific antibodies GMT. Neutralizing antibodies GMT. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |