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: "Computer randomisation was done with full allocation concealment within the secure web platform"
Comment: Allocation sequence random. Allocation sequence concealed. A subgroup of 10/543 (1.8%) participants in the intervention arm that received a booster dose and extensive follow-up for safety and immunogenicity purposes were not randomised. Baseline characteristics appear to be similar between arms. Risk assessed to be low. |
| Deviations from intervention |
Low |
Quote: "Participants enrolled in groups 1, 2 and 4 will be blinded to the arm they have been allocated to, whether investigational vaccine or control. The trial staff administering the vaccine will not be blinded." Quote: "Additional steps may be taken to keep clinical investigators assessing primary endpoints blinded to group allocation, where this is possible and practical to do so. A designated member of the clinical team may be unblinded for the purposes of safety reporting procedures." Quote: "Participants enrolled in group 3 will not be randomised or blinded" Comment: Not fully blinded study (1% of participants and those administering the vaccine were not blinded, unblinding of investigator was allowed for safety reporting procedures). Prophylactic paracetamol administration was reported and was balanced between groups. One participant randomised to control received intervention vaccine. This single deviation was not considered sufficient to affect the results. SAFETY Data were analyzed approriately using intention-to-treat analysis. Risk assessed to be low for outcomes: Serious adverse events. 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 outcome: Serious adverse events. |
| Missing outcome data |
Low |
Comment: 1067 randomized/ 1067 analyzed for serious adverse events/ 137 analyzed for cellular response
SAFETY Data available for all participants. Risk assessed to be low for the outcome: Serious adverse events. |
| Measurement of the outcome |
Low |
Quote: "Clinical investigators and the laboratory team remained blinded to group allocation"
Comment: Blinded study (outcome assessor). Risk assessed to be low for the outcome: Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective trial registry ( March 27, 2020) was available. The protocol and statistical analysis plan were available but retrospective. The report presented limited, planned interim analyses.
Outcome was pre-specified in the registry Result was not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcome: Serious adverse events. |
| Overall risk of bias |
Low |