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 were randomly assigned ... by using an interactive web response randomisation system. The randomisation lists were generated by an independent statistician using SAS software (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: "This study is an open-labeled trial, so both the participants and investigators were aware of the treatment allocations after the randomisation"
Comment: Unblinded study (participants and personnel/carers). Deviations from intended intervention arising because of the study context: Quote: "One participant randomised to the high-dose aerosolized Ad5-nCoV vaccine group, but was administrated with a dose of the CoronaVac by mistake, whom was included in the ITT analysis in the high-dose aerosolized Ad5-nCoV vaccine group for safety, and immunogenicity evaluation" We consider one participant cross-over negligible. Hence, deviations did not arise because of the trial context. SPECIFIC ANTIBODY GMT.LOCAL ADVERSE EVENTS. SYSTEMIC ADVERSE EVENTS. SERIOUS ADVERSE EVENTS ITT analysis was performed in the safety outcomes and Specific anibody GMT. 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 the outcomes: Specific antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. SPECIFIC ANTIBODY GMT (>90D). NEUTRALIZING ANIBODY SEROCONVERSION RATE. NEUTRALIZING ANIBODY SEROCONVERSION RATE (>90). NEUTRALIZING ANTIBODY GMT. NEUTRALIZING ANTIBODY GMT (>90D). NEUTRALIZING ANIBODY SEROCONVERSION RATE OMICRON. NEUTRALIZING ANIBODY SEROCONVERSION RATE OMICRON (>90D).NEUTRALIZING ANTIBODY GMT OMICRON. NEUTRALIZING ANTIBODY GMT OMICRON (>90D) . Modified ITT analysis was performed in the outcome Neutralizing antibody GMT Quoter: "In this report, we revealed the neutralising antibodies (NAbs) against live wild-type SARS-CoV-2 and omicron variant and RBD-specific IgG antibodies in serum of the first 40 participants in each of the three treatment groups" As we are assessing the effect of assignment to intervention, the analysis method performed on these safety outcomes was considered inappropriate. There was probably no substantial impact of failure to analyze participants according to their randomized assignment due to balance between arms. Risk assessed to be some concerns for the outcomes: Specific antibody GMT (>90D). Neutralizing antibody seroconvertion rate. Neutralizing antibody seroconvertion rate (>90D). Neutralizing antibody GMT. Neutralizing antibody GMT (>90D). Neutralizing antibody seroconvertion rate Omicron. Neutralizing antibody seroconvertion rate Omicron (>90D). Neutralizing antibody GMT Omicron. Neutralizing antibody GMT Omicron (>90D). |
| Missing outcome data |
Low |
Comment: 423 participants randomized; 420 participants analyzed for safety aoutcomes and Specific antibody GMT/117 participants analyzed for the outcomes: Specific antibody GMT (>90D). Neutralizing antibody seroconvertion rate. Neutralizing antibody seroconvertion rate (>90D).Neutralizing antibody GMT. Neutralizing antibody GMT (>90D). Neutralizing antibody seroconvertion rate Omicron. Neutralizing antibody seroconvertion rate Omicron (>90D). Neutralizing antibody GMT Omicron. Neutralizing antibody GMT Omicron (>90D).
SPECIFIC ANTIBODY GMT.LOCAL ADVERSE EVENTS. SYSTEMIC ADVERSE EVENTS. SERIOUS ADVERSE EVENTS Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Specific antibody GMT. Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. SPECIFIC ANTIBODY GMT (>90D). NEUTRALIZING ANIBODY SEROCONVERSION RATE. NEUTRALIZING ANIBODY SEROCONVERSION RATE (>90). NEUTRALIZING ANTIBODY GMT. NEUTRALIZING ANTIBODY GMT (>90D). NEUTRALIZING ANIBODY SEROCONVERSION RATE OMICRON. NEUTRALIZING ANIBODY SEROCONVERSION RATE OMICRON (>90D).NEUTRALIZING ANTIBODY GMT OMICRON. NEUTRALIZING ANTIBODY GMT OMICRON (>90D) . Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: Only 40 first patients of the cohort analyzed for this outcome. This risk of bias was already taken into account in domain 2. Risk assessed to be low for the outcomes: Specific antibody GMT (>90D). Neutralizing antibody seroconvertion rate. Neutralizing antibody seroconvertion rate (>90D). Neutralizing antibody GMT. Neutralizing antibody GMT (>90D). Neutralizing antibody seroconvertion rate Omicron. Neutralizing antibody seroconvertion rate Omicron (>90D). Neutralizing antibody GMT Omicron. Neutralizing antibody GMT Omicron (>90D). |
| 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). SPECIFIC ANTIBODY GMT. SPECIFIC ANTIBODY GMT (>90D). NEUTRALIZING ANIBODY SEROCONVERSION RATE. NEUTRALIZING ANIBODY SEROCONVERSION RATE (>90). NEUTRALIZING ANTIBODY GMT. NEUTRALIZING ANTIBODY GMT (>90D). NEUTRALIZING ANIBODY SEROCONVERSION RATE OMICRON. NEUTRALIZING ANIBODY SEROCONVERSION RATE OMICRON (>90D).NEUTRALIZING ANTIBODY GMT OMICRON. NEUTRALIZING ANTIBODY GMT OMICRON (>90D) . Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Specific antibody GMT. Specific antibody GMT(>90D). Neutralizing antibody seroconvertion rate. Neutralizing antibody seroconvertion rate (>90D). Neutralizing antibody GMT. Neutralizing antibody GMT (>90D). Neutralizing antibody seroconvertion rate Omicron. Neutralizing antibody seroconvertion rate Omicron (>90D). Neutralizing antibody GMT Omicron. Neutralizing antibody GMT Omicron (>90D). 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 registry was 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: Local adverse events. Systemic adverse events. Specific antibody GMT. Specific antibody GMT (>90D). Neutralizing antibody seroconvertion rate. Neutralizing antibody seroconvertion rate (>90D). Neutralizing antibody GMT. Neutralizing antibody GMT (>90D). Neutralizing antibody seroconvertion rate Omicron. Neutralizing antibody seroconvertion rate Omicron (>90D). Neutralizing antibody GMT Omicron. Neutralizing antibody GMT Omicron (>90D). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |