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: “Healthy seronegative participants 18–55 years of age who met all inclusion criteria and no exclusion criterion (see the protocol in the Supplementary Information for all inclusion/exclusion criteria) were enrolled between 13 July 2020 and 9 August 2020, and were randomized into nine groups in a ratio of 1:1:1:1:1:1:1:1:1 using a permuted block randomization schedule (pre-specified 20 participants per group).”
Comment: Allocation sequence random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote: "The participants and the personnel collecting the safety information and testing laboratories remained blinded to treatment allocation."
Comment: Blinded study (participants and personnel/carers). No participant cross-over. SAFETY Data were analyzed using intention-to-treat analysis. 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: Mortality. Adverse events. Withdrawal due to adverse events. Serious adverse events. IMMUNOGENICITY Per-protocol analysis was performed on the outcomes. 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. Risk assessed to be some concerns for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. |
| Missing outcome data |
Low |
Comment: Data from interim analysis.
180 participants randomized; 180 participants analyzed for safety, 166 - 177 participants analyzed for immunogenicity. SAFETY Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality. Adverse events. Withdrawal due to adverse events. Serious adverse events. IMMUNOGENICITY Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Missingness could not depend on the true value of the outcome (accounted for in domain 2). Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. |
| 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: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Adverse events. Withdrawals due to adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The trial registry, protocol and statistical analysis plan were available. 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: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Adverse events. Withdrawal due to adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |