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: "Participants were randomly assigned in a blinded manner using the centralized Interactive Response Technology according to pre-generated randomization schedules" Comment: Allocation sequence random. Allocation sequence concealed. Minor imbalances in baseline characteristics appear to be compatible with chance. Risk assessed to be low. |
| Deviations from intervention |
Some concerns |
Quote: "To maintain the blind, placebo vaccination via the intramuscular route was included, and unblinded site personnel managed vaccine logistics, preparation, and administration (if necessary) so as to maintain the blind from the remainder of the site personnel and participants." Comment: Not fully blinded study (participants and some personnel were blinded). Two participants crossed over from placebo to vaccine group. This deviation was considered negligible among 2684 participants analysed for efficacy outcomes. Per-protocol analysis was performed on the efficacy outcome evaluated in this cohort (as planned in the trial protocol). Reasons for exclusion: Seropositivity at baseline (849 vS 873), SARS-CoV-2 positivity before day 28 (97 vS 78), Did not received both dosis (24 vs 31), had important protocol deviations (4 vS 7), Lost to follow-up (6 vs 9), was withdrawn by physsicians (1 vs 0), becae pregnant (2 vs 3), Withdrew with no reason reported (10 vs 15), Had adverse event, not related to vaccine (1 vs 0). 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
4406 participants randomized; 2684 participants analyzed for efficacy. Data available for 61% of population for efficacy. 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: 44 cases identified /41 cases sequenced and classified 93.18% of cases analyzed for variants. Quote: “Of these participants, 41 (93%) had samples that were adequate for whole-genome sequencing; samples from 3 participants in the placebo group could not be sequenced” 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.(23 June 2020). The outcome Confirmed symptomatic B.1.351 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 (variant) |
| Overall risk of bias |
Some concerns |