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 |
Some concerns |
Quote: "no specific randomisation was used when allocating participants to the vaccinations schedule cohorts" "In phase 1, participants in blocks 1 and 2 in each schedule cohort were randomly assigned (2:1) to either CoronaVac or placebo" "The randomisation codes for each vaccination schedule cohort were generated individually, using block randomisation with a block size of six in phase 1 and a block size of five in phase 2, using SAS software (version 9.4). The randomisation code was assigned to each participant in sequence in the order of enrolment, and then the participants received the investigational products labelled with the same code" Comment: No specific randomisation between schedule cohorts or between low-dose and high-dose arms. The allocation sequence between vaccine groups and placebo was generated adequately. Unclear allocation concealment. Risk assessed as some concerns. |
| Deviations from intervention |
Low |
Quote: "The vaccine and the placebo are identical in appearance. All participants, investigators, and laboratory staff were masked to treatment allocation." (publication) "Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)" (trial registry)
Comment: Blinded study (patients, care providers, and investigators). SAFETY 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. IMMUNOGENICITY Per-protocol analysis was performed on the outcomes. Reasons for exclusion: There were no exclusions. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response |
| Missing outcome data |
Low |
Comment: 144 participants randomized; 143 participants analyzed for safety outcomes; 144 participants analyzed for specific and neutralizing outcomes; 143 participants analyzed for cellular response. Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Cellular response. Local adverse events. Systemic adverse events. 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: Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan were not available at the time of data extraction. The prospective trial registry was available (April 20, 2020) 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: Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Adverse events. |
| Overall risk of bias |
Some concerns |