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: "Randomisation lists were prepared by the study statistician (MV) using block randomisation, stratified by study site and study group, and uploaded into to the secure web platform used for the study electronic case report form (REDCap version 9.5.22) for COV001, COV002, and COV003." Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: "single blind"; "Participants will be blinded to the arm they have been allocated to"; "The trial staff administering the vaccine will not be blinded"; "The trial staff administering the vaccine prepared vaccines out of sight of the participants and syringes were covered with an opaque material until ready for administration to ensure masking of participants."
Comment: Blinded study (participants only). No participant cross-over. SAFETY Intention to treat analysis was performed on the safety outcomes. As we are assessing the effect of assignment to intervention, this analysis method was considered, hence risk of bias would be considered low for safety outcomes. EFFICACY Per-protocol analysis was performed on the efficacy outcome evaluated in this cohort (as planned in the trial protocol). Reasons for exclusions: Not enrolled in efficacy cohort (465 vs 51); Participants not in a group that received SD/SD or LD/SD vaccines (51 vs 49); Baseline seropositivity results unavailable (31 vs 27); Baseline seropositivity results positive (72 vs 66); Vaccine administration errors (6 vs 0); Less than 15 days of follow up accrued post second dose (1080 vs 1027); PCR+ test ? 14 days post-second dose (30 vs 25) As we are assessing the effect of assignment to intervention (intent-to-treat effect), this domain was evaluated as some concerns for efficacy outcome: Confirmed symptomatic COVID |
| Missing outcome data |
Low |
Comment: Data from interim analysis.
10,673 participants randomized; 7548 participants analyzed. Data available for 71% of population. Most patients were excluded because the planned analysis was a per-protocol analysis and the bias had been taken into account in domain 2 Risk assessed to be low for the outcome: Confirmed symptomatic COVID. |
| Measurement of the outcome |
Low |
Quote: "All cases of COVID-19 were reviewed by two members of a masked independent clinical review team who assessed clinical details, including medical history, symptoms, adverse events, and swab results, and assigned severity scores according to the WHO clinical progression scale" Comment: The participant allocations were blinded to assessors of COVID cases and symptoms. Risk assessed to be low for the outcome: Confirmed symptomatic COVID. |
| Selection of the reported results |
Low |
Comment: The protocol, global statistical analysis plan for pooling study data, and registry 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 the outcome: Confirmed symptomatic COVID. |
| Overall risk of bias |
Some concerns |