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: “Volunteers were randomly assigned to immunization with CoronaVac or injection with placebo in a 1:1 ratio. A subgroup of volunteers was assigned to the immunogenicity arm and randomly received CoronaVac or placebo (3:1 ratio).
Randomization was done using a sealed enveloped system integrated into the
electronic Case Report Forms (eCRF) in the OpenClinica platform”
Comment: Authors report 1:1 allocation ratio for intervention/control group. However, in the flow chart and result tables there are 290 participants in the vaccine group and 164 in the control group. Comment: Allocation sequence concealed. Allocation sequence unclear. Baseline characteristics not reported by arm. Risk assessed as some concerns. |
| Deviations from intervention |
Some concerns |
Quote: "A study nurse administered intramuscularly in the deltoid area unblinded ready-to-use syringes with
CoronaVac or placebo (visually indistinguishable among them). To avoid any influence on the volunteers, the interaction with the nurse was restricted only to
immunization. Then, safety evaluations were performed by the blind clinical team" (published paper) "Masking: Quadruple (Participant, Care Provider, Investigator, Outcome Assessor)" (registry)
Comment: Blinded study (participants, investigators, outcome assessors). SAFETY All randomized participants who received at least one dose were analyzed 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 outcome: Local adverse events. Systemic adverse events. Serious adverse events. IMMUNOGENICITY A subset of participants was analyzed for immunogenicity outcomes after receiving the second dose. 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. Risk assessed to be some concerns for the outcome: Neutralizing antibody GMT. |
| Missing outcome data |
Some concerns |
Data from interim analysis.
SAFETy Comment: 434 patients randomized; 434 patients analyzed Data available for all participants randomized. Risk assessed to be low for outcome: Local adverse events. Systemic adverse events. Serious adverse events. IMMUNOGENICITY Comment: Unclear number of participants randomized/ 83 participants analyzed. No information on whether data were available for all randomized participants. No evidence that the result is not biased. No information on whether missingness could or is likely to depend on the true value of the outcome. Risk assessed to be some concerns for the outcomes: Neutralizing antibody GMT. |
| 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: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective trial registry (Dec 23rd 2020) was available.
Substantial changes were made to the original trial registry regarding participant characteristics, the intervention comparison, blinding, and outcomes. However, the interim analysis reported in the pre-print adheres to the original trial registry. Therefore, for the interim analysis, the results were not selected from multiple outcome measurements or analyses of the data. The interim results are analyzed as pre-specified. Risk assessed to be low for the outcome: Neutralizing antibody GMT. Local adverse events. Systemic adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |