| 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)." 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. Per-protocol analysis was performed on the efficacy outcomes (as planned in the trial protocol). Reasons for exclusions: Baseline seropositivity results unavailable; Baseline seropositivity results positive; Vaccine administration errors; Less than 15 days of follow up accrued post second dose; PCR+ test ≤ 14 days post-second dose As we are assessing the effect of assignment to intervention (intent-to-treat effect), this domain was evaluated as some concerns for efficacy outcomes. |
| Missing outcome data |
Low |
Comment: Data from interim analysis.
10,002 participants randomized; 4088 participants analyzed. Data available for 41% 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 |