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: "Unblinded statisticians (Cytespace Research and Octalsoft) were involved in designing the randomisation plan and the interactive web response system(IWRS) system for the study. The randomisation plan,stratified for the presence or absence of chronic conditions, was used to generate treatment allocation. The master randomisation list, containing the randomisation number and intended treatment allocation, as well as the kit code, was sent to the IWRS and kits were despatched to the sites according to the IWRS by an unblinded statistician from the CRO tasked with labelling of vaccine vials and the generation of the master randomisation code. Participants were assigned a computer-generated randomisation code and each vial was labelled with a unique code that ensured appropriate masking. The IWRS system assigned the same treatment group for the second visit. ”
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 |
Quote: “Double-blind. Participants, investigators, study coordinators, study-related personnel, and the sponsor were masked to the treatment group allocation, and masked study nurses at each site were responsible for vaccine preparation and administration.”
Per-protocol analysis was performed on the efficacy outcomes (as planned in the trial protocol). Reasons for exclusions were balanced between treatment groups: Withdrawal of consent, BBV152B = 316/Placebo = 303; Physician decision, 9/15; Lost to follow up, 296/285; Adverse event, 13/6; Logistical problem, 14/22; Death, 4/3; Pregnancy, 1/1; RT-PCR positive before dose 2, 26, 15, Other, 6/9; Unknown, 181/193. 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 |
Low |
Comment: 25798 participants randomized/16973 participants analyzed
Data not available for all or nearly allcases Reasons for missing data: Most patients were excluded because the planned efficacy analysis was a per-protocol analysis and the bias has been taken into account in domain 2. Missingness could not depend on the true value of the outcome. Variant classification: 130 cases identified/ 130 cases sequenced 100% of cases sequenced for variants. Data available for all or nearly all cases. 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 (Nov 20,2020).
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 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 |