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 |
Comment: single-blind trial
Per-protocol analysis was performed on the efficacy outcomes (as planned in the trial protocol). Reasons for exclusions: In non-randomised open-label group; In HIV cohorts; Not enrolled in an efficacy cohort; Not in SD/SD or LD/SD vaccine group; 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. Risk assessed to be some concerns for outcomes: CConfirmed symptomatic against Alpha variant. |
| Missing outcome data |
Some concerns |
Comment: 10811 participants vaccinated/ 8534 included in primary efficacy analysis.
EFFICACY AGAINST VARIANTS
Variant sequence: 269 cases identified /147 cases sequenced and classified 54.64% of cases analyzed for variants. Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons for missing data:"Sample did not enter sequencing pipeline, was destroyed, or sequencing results are yet to be obtained. No information on whether missingness could or is likely to depend on the true value of the outcome. Risk assessed to be some concerns for the outcome: Confirmed symptomatic against Alpha variant. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
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 against Alpha variant. |
| Selection of the reported results |
Some concerns |
Comment: The prospective protocol, SAP and prospective registry were available.
The outcome Confirmed symptomatic against Alpha 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 Risk assessed to be some concerns for the outcome: Confirmed symptomatic against Alpha variant. |
| Overall risk of bias |
Some concerns |