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: “Eligible participants were randomly assigned (1:1:1:1:1) to one of five groups by computer-generated randomisation sequences.”
Comment: Allocation sequence random. No information on allocation concealment. |
| Deviations from intervention |
Low |
Quote: “Open-label. Participants could not be masked to group assignment because of the nature of the treatment.”
No participant cross-over. As we are assessing the effect of assignment to intervention, the (modified) intention-to-treat analysis method performed on these outcomes, was considered appropriate. Risk assessed to be low for outcomes: GMT sAb. GMT nAb. Cellular response. Systemic adverse events. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
130 participants randomized; 130 participants analyzed for safety; 128 participants analyzed for immunogenicity Data available for > 95% of population. Risk assessed to be low for outcomes: GMT sAb. GMT nAb. Cellular response. Systemic adverse events. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Quote: "Open-label. Laboratory staff who analysed immunological outcomes were masked to treatment allocation during the whole study"
Risk assessed to be low for the outcomes: GMT sAb. GMT nAb. Cellular response. The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prostpectve registry (17, Sep 2020 ), statistical analysis plan and protocol (27, Sep 2020) were available.
Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for outcomes: GMT sAb. GMT nAb. Cellular response. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |