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: "Randomization was performed by the Interactive Web-based Response System (IWRS) of the Omega Clinical Research Organization... Unblinded nurses were assigned to prepare the study vaccines for injection... Each enrolled participant was assigned a code and the unblinded nurse stuck the coded labels on the syringes and prepared labeled syringes filled with the study vaccine in a separate room to make sure that the contents of the syringes were not visible. Access to the randomization code was strictly controlled by the nurse in the room where the study vaccines were located."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: "observer-blinded" trial.
Comment: Blinded study (participants and personnel/carers). Per-protocol analysis was performed on all outcomes. Reasons for exclusion: had evidence of current or prior SARS-CoV-2 infection at baseline (186 vs 189 excluded, including for safety & efficacy outcomes); or only for efficacy: COVID within 14 days after the second study vaccination (44 vs 36 participants); did not receive two doses of the vaccine within the predefined window in the protocol (42 vs 44), or had protocol deviations to affect efficacy and safety assessment. 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 due to similar proportions between groups. Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID, Mortality, Local adverse events, Systemic adverse events, Adverse events, and Serious adverse events. |
| Missing outcome data |
Low |
Comment: 1290 participants randomized; 915 participants analyzed for safety outcomes; 732 participants analyzed for Confirmed COVID-19.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. CONFIRMED SYMPTOMATIC COVID-19 Reasons: most due to protocol violations that were accounted for in domain 2; others were 1% of missing only: 6 vs 4 withdrawals, and 3 vs 4 lost to followup. Missingness could not depend on the true value of the outcome. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Mortality, Local adverse events, Systemic adverse events, Adverse events, and Serious adverse events. Reasons: all were due to protocol violations that were accounted for in domain 2. Missingness could not depend on the true value of the outcome. Risk assessed to be low for the outcomes: Mortality, Local adverse events, Systemic adverse events, Adverse events, and Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: 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 symptomatic COVID, Mortality, Local adverse events, Systemic adverse events, Adverse events, and Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry were available (dated June 28, 2021).
Outcome pre-specified. Results were 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 symptomatic COVID, Mortality, Local adverse events, Systemic adverse events, Adverse events, and Serious adverse events. |
| Overall risk of bias |
Some concerns |