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)" (from Voysey, Lancet, 2020)
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. Risk assessed to be low |
| Deviations from intervention |
Some concerns |
Quotes: “Participants, clinical investigators and laboratory staff were blinded to vaccine allocation. Following emergency use authorisation of ChAdOx1 nCoV-19 and an inactivated SARS-CoV-2 viral vaccine in Brazil on 17th January 2021, all trial participants were unblinded to vaccine allocation but remained in the trial and continued with follow up” "Cases were included in the efficacy analysis if a lineage was obtained from processing the swab taken for diagnosis, COVID-19 symptoms occurred on day 15 after the second dose or later, and before the participant was unblinded as to the vaccines they had received. In addition, some participants received a COVID-19 vaccine outside of the trial and were censored in the analysis at this time point."
Comment: Blinded study (participants and personnel/carers) Per-protocol analysis was performed on the outcomes. Reasons for exclusion: ChAdOx1 group: Vaccination error (n=2), Follow up time less than 15 days after 2nd dose (n=113), Did not receive 2nd dose (n=137), Seropositive or unavailable serostatus at baseline (n=183); control: Follow up time less than 15 days after 2nd dose (n=182), Did not receive 2nd dose (n=193), Seropositive or unavailable , serostatus at baseline (n=173) As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. There was probably no substantial impact of failure to analyze participants according to their randomized assignment. Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID-19 (variant) |
| Missing outcome data |
Low |
Comment: 10416 participants randomized; 9433 participants analyzed.
Data not available for all or nearly all participants randomized; 9.4% missing data. No evidence that the result is not biased. Missing data were due to protocol violations and are accounted for in domain 2 Variant classification: 299 cases identified/ 229 cases sequenced and classified. 76.58% of cases sequenced for variants. Data not available for all or nearly allcases No evidence that the result is not biased. Quote:"236 (77%) of these primary cases had sufficient intact specimen for lineage assignment through sequencing or genotyping. Some participants had more than one positive swab for the same event". 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 prospective registry was available (11 June, 2020).
The outcome Confirmed symptomatic against Gamma 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 |