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 aged 18 years or older were randomly assigned (4:1) to receive the QazCovid-in® vaccine or placebo with complete concealment. The vaccine and placebo were assigned codes by block randomisation using a computerised randomisation schedule that was generated by an independent statistician using SAS Programming (version 9.4).”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: “Single-blind”
Partially blinded study (participants were blinded). Deviations from intended intervention arising because of the study context: No participant cross-over. Hence, deviations did not arise because of the trial context. LOCAL ADVERSE EVENTS. SYSTEMIC ADVERSE EVENTS. ADVERSE EVENTS. SERIOUS ADVERSE EVENTS. MORTALITY. CONFIRMED SYMPTOMATIC COVID. CONFIRMED SEVERE COVID. Those who received at least one dose of the intervention (100% of participants) were anaysed. As we are assessing the effect of assignment to intervention, the analysis method performed on these outcomes was considered appropriate. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. Mortality. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. SPECIFIC ANTIBODY GMT. NEUTRALIZING ANTYBODY GMT. Per-protocol analysis was performed on the outcomes. Reasons for exclusion: withdrown (68 vs 20), Adverse events (12 vs 2), pregnancy 9 vs 4), lost to follow up (12 vs 0), refused (25 vs 13), died (0 vs 1). 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 balance between groups Risk assessed to be some concerns for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. |
| Missing outcome data |
Some concerns |
Comment: 3000 participants randomized; 3000 participants analyzed for reactogenicity; 2911 participants analyzed for immunogenicity; 2835-3000 participants analyzed for efficacy.
LOCAL ADVERSE EVENTS. SYSTEMIC ADVERSE EVENTS.ADVERSE EVENTS. SERIOUS ADVERSE EVENTS. MORTALITY. SPECIFIC ANTIBODY GMT. NEUTRALIZING ANTYBODY GMT. Data available for all or nearly all participants randomized for reactogenicity and immunogenicity. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. CONFIRMED SYMPTOMATIC COVID. CONFIRMED SEVERE COVID. No evidence that the result is not biased. Reasons: withdrew (50 vs. 9), were pregnant (9 vs. 4), had adverse event (12 vs. 2), lost to follow-up (5 vs. 0), died (0 vs. 1), refused (31 vs. 13), withdrawn by physician (18 vs. 11). Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome due to similar proportions and reasons for missing data. Risk assessed to be some concerns for the outcomes: Confirmed COVID. Confirmed symptomatic COVID. Confirmed severe COVID. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) MORTALITY, SPECIFIC ANTIBODY GMT, NEUTRALIZING ANTIBODY GMT Mortality and immunogenicity are observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality. Specific antibody GMT. Neutralizing antibody GMT. CONFIRMED SYMPTOMATIC COVID, CONFIRMED SEVERE COVID This outcome requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID LOCAL, SYSTEMIC, ADVERSE and SERIOUS ADVERSE EVENTS The authors reported on adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective protocol (date December 17th, 2020) and registry (date December 31th, 2020) were available
Outcomes 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. Confirmed severe COVID. Mortality. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |