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 theinteractive web response system(IWRS) system for the study. Therandomisation plan,stratified for thepresence 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 IWRSand kits were despatched to the sites according to the IWRSby an unblinded statistician from the CROtasked 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.
Allocation sequence random. allocation sequence concealed. Risk assessed to be low. |
| Deviations from intervention |
Some concerns |
Quote:"Participants, investigators, study coordinators, study-related personnel, and the sponsor were masked to the treatment group allocation, and masked study nursesat each site were responsible for vaccine preparation and administration."
Comment: Blinded study (participants, personnel, investigators). All randomized participants who received at least one dose were analysed for safety outcomes. As we are assessing the effect of assignment to intervention, the analysis method performed on these safety outcomes, was considered appropriate. Risk assessed to be low for outcomes: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. EFFICACY All randomized participants who received at least one dose were analysed for the outcome: Mortality. As we are assessing the effect of assignment to intervention, the analysis method performed on this outcome, was considered appropriate. Risk assessed to be low for the outcome: Mortality. Per-protocol analysis was performed on the outcomes: Confirmed COVID, Confirmed symptomatic COVID and Confirmed severe COVID (as planned in the trial protocol). As we are assessing the effect of assignment to intervention (intention-to-treat effect), we considered that the data were analyzed inappropriately. Reasons for exclusions were balanced: Did not received dose 1 (20 vS 25), Did not received dose 2 (658 vS 676). Positive for anti-SARS-CoV-2 IgG (3932 Vs 3886),Positive for SARS-CoV-2 by PCR (108 Vs 105). 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 COVID. Confirmed symptomatic COVID. Confirmed severe COVID. |
| Missing outcome data |
Some concerns |
Comment: 25798 participants randomized/25753 participants analyzed for safety/25753 participants analyzed for Mortality/16973 participants analyzed for efficacy SAFETY Data available for all or nearly all participants randomized for the safety outcomes. Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Adverse events. Withdrawals due to adverse events. Serious adverse events EFFICACY Data available for all or nearly all participants randomized for the outcome Mortality. Risk assessed to be low for the outcome: Mortality Data not available for all or nearly all participants randomized for the outcomes: Confirmed COVID-19. Confirmed symptomatic COVID-19. Severe or critical COVID-19. 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. Risk assessed to be low for the outcomes: Confirmed COVID-19. Confirmed symptomatic COVID-19. Severe or critical COVID-19. |
| Measurement of the outcome |
Low |
Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Confirmed COVID. Confirmed symptomatic COVID. Confirmed severe COVID. Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
The prospective register (Nov 20,2020) was available.
The outcomes Confirmed COVID-19, Confirmed symptomatic COVID-19, Severe or critical COVID-19, Local adverse events, Systemic adverse events, Adverse events and Serious adverse events were pre-especfied. The outcome overall mortality was not pre-specified but we do not consider the reporting of this outcomes to be selective since they should be reported even if not planned. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcomes:Confirmed COVID. Confirmed symptomatic COVID. Confirmed severe COVID. Mortality. Local adverse events. Systemic adverse events. Unsolicited adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |