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 subjects were randomly assigned at a ratio of 1:1 into two study arms to receive either 3 μg/0.5 mL dose of inactivated SARS-CoV-2 vaccine or placebo on day 0 and 14. The randomization list was generated automatically using the website, www.sealedenvelope.com, and the vaccinated arms were grouped into three different batch numbers (batch 1/batch 2/batch 3) of SARS-CoV-2 vaccine. The subjects were randomized and vaccinated per treatment group by an unblinded team.”
Comment: Allocation sequence random for the whole study but unclear for the immunogenicity subset. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. Risk assessed to be some concerns. |
| Deviations from intervention |
Some concerns |
Quote: “Double-blind”
Comment: Blinded study (participants and outcome assessors) SAFETY, IMMUNOGENICITY Safety and immunogenicity outcomes were monitored in a safety subset (first 540 partcipants randomized. 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 all participants according to their randomized assignment Risk assessed to be some concerns for the outcomes: Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. EFFICACY The efficacy results are based on preliminary efficay data from all the participants randomized. As we are assessing the effect of assignment to intervention, the analysis method performed on these efficacy outcomes, was considered appropriate Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. |
| Missing outcome data |
Low |
Comment: 1620 participants randomized; 1602 participants analyzed for efficacy; 540 participants analyzed for safety and 535 for immunogenicity.
SAFETY, IMMUNOGENICITY Data not available for all or nearly all participants randomized for safety and immunogenicity. No evidence that the result is not biased. Reasons: 1.5% and 0.7% withdrew or were withdrawn from the study. Missingness could not depend on the true value of the outcome: immunogenicity and 7-day safety were only assessed in a pre-defined subset of the first 540 randomized participants. Risk assessed to be low for the outcomes:Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. EFFICACY Data available for nearly all participants randomized for efficacy. Risk assessed to be low for the outcomes: Confirmed symptomatic COVID. Confirmed severe COVID. |
| 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. Confirmed severe COVID. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The prospective trial registry was available (August 11, 2020).
SEVERE COVID-19 LOCAL ADVERSE EVENTS, SYSTEMIC ADVERSE EVENTS 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 severe COVID. Specific antibody GMT. Neutralizing antibody GMT. Local adverse events. Systemic adverse events. CONFIRMED SYMPTOMATIC COVID-19, SPECIFIC ANTIBODIES GMT, NEUTRALIZING ANTIBODIES GMT Outcome not pre-specified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Confirmed symptomatic COVID. Specific antibodies GMT, Neutralizing antibodies GMT; |
| Overall risk of bias |
Some concerns |