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. Risk assessed to be low. |
| Deviations from intervention |
Some concerns |
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. No participant cross-over. 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 (intention-to-treat effect), we considered that the data were analyzed inappropriately. There was no substantial impact of failure to analyze participants according to their randomized assignment Risk assessed to be some concerns for the outcome: Confirmed symptomatic COVID-19 (variant) |
| Missing outcome data |
Some concerns |
Comment: Data from interim analysis.
10,673 participants randomized; 8534 participants analyzed. Data not available for all or nearly allcases Most patients were excluded because the planned analysis was a per-protocol analysis and the bias had been taken into account in domain 2. Variant classification: 269 cases identified /147 cases sequenced and classified 54.64% of cases analyzed for variants Quote: "“A limitation of this study is that sequences could not be obtained from all positive swab samples due to logistical constraints in laboratories processing multiple clinical samples during the COVID-19 pandemic" Missingness could not depend on the true value of the outcome Risk assessed to be low for the outcome: Confirmed symptomatic COVID-19 (variant) |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups.>br/>Blinded study (outcome assessor). It is not clear if cases were unblinded at the moment of the identification of the variant however, we consider these results can't be affected by the knowledge of the intervention allocation. Risk assessed to be low for the outcome: Confirmed symptomatic COVID-19 (variant) |
| Selection of the reported results |
Some concerns |
Comment: The protocol, SAP and prospective registry were available (May 26, 2020). The outcome Confirmed symptomatic B.1.117 variant was not prespecified in the registry. Post-hoc anlysis No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Confirmed symptomatic COVID-19 (variants) |
| Overall risk of bias |
Some concerns |