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: “Eligible participants were randomly allocated to the Ad5-nCoV group or the Placebo group, in a 3:1 ratio, by an independent statistician using a validated system including a pseudorandom number generator with a seed value; allocation used block randomisation and stratification by study site. ”
Comment: Allocation sequence random Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance |
Deviations from intervention |
Some concerns |
Quote: “Double-blinded. Neither the investigators nor participants were aware of the group assignment.”
Comment: Blinded study (participants and personnel/carers) Data for the safety and efficacy outcomes were analyzed using modified intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Per-protocol analysis was performed on the immunogenicity outcomes. Reasons for exclusion: COVID-19 before day 14, prohibited therapy, follow up visits outside window, missing data, no initial immunogenicity data; cellular response measured in a subset. 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 / probably no substantial impact of failure to analyze participants according to their randomized assignment due to blinding and relative balance between groups. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID (partial vaccination). Mortality. Local adverse events. Systemic adverse events. Adverse events. Withdrawals due to adverse events. Serious adverse events. Risk assessed to be some concerns for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. |
Missing outcome data |
Low |
Comment: 500 participants randomized; 496 participants analyzed for safety; 481 participants analyzed for efficacy; 419 participants analyzed for immunogenicity; 69 participants analyzed for cellular response.
Data available for all or nearly all participants randomized for safety, efficacy. Data not available for all or nearly all participants randomized for immunogenicity, cellular response. No evidence that the result is not biased. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. This potential source of bias has been taken into account in domain 2. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID (partial vaccination). Mortality. Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Local adverse events. Systemic adverse events. Adverse events. Withdrawals due to adverse events. 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 (partial vaccination). Mortality. Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Local adverse events. Systemic adverse events. Adverse events. Withdrawals due to adverse events. Serious adverse events. |
Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and prospective registry were available.
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 outcome: Confirmed symptomatic COVID (partial vaccination). Mortality. Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Local adverse events. Systemic adverse events. Adverse events. Withdrawals due to adverse events. Serious adverse events. |
Overall risk of bias |
Some concerns |