Trial NCT04445194
Publication Yang S, Lancet, 2021
Primary outcome on the report: For the phase 1 trial, the primary outcome was the safety of the COVID-19 vaccine;Safety outcomes were the occurrence of adverse events between the first injection to 30 days after the final injection, including all adverse events, adverse events related to vaccination, adverse events at grade 3 and worse, and adverse events leading to withdrawal of participants.

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: "The randomisation statisticians used SAS statistical software (version 9.4) to generate the random table of participants in each dose group. These randomisation statisticians were not allowed to participate in other related work of these clinical trials and not allowed to disclose the blind code to any personnel participating in this clinical trial. The participants were randomly assigned to the experimental vaccine group or the placebo group according to the block randomisation method, with the block and block size of 5 and 5, respectively, in phase 1 trial, and of 75 and 12, respectively, in phase 2 trial. Investigators at trial site assign study numbers strictly according to the order of screening sequence of eligible subjects, and experimental vaccines were obtained and administered according to the numbers."
Comment: Allocation sequence random. Allocation concealed.
Imbalances in baseline characteristics appear to be compatible with chance
Deviations from intervention
Low 		Quote: “The participants, field investigators and laboratory team were always blinded to group allocation during the trial.”
Comment: Double-blinded study (patients and physicians).
Data were analyzed using intention-to-treat analysis for safety.
Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Adverse events. Serious adverse events. Withdrawal due to adverse events
Missing outcome data
Some concerns 		Comment: 50 randomized; 50 analyzed for adverse events.
However 2 vs 5 vs 2 participats withdrew from the trial.
Data not available for all or nearly all participants randomized
No evidence that the result is not biased.
Reasons for missing data: 6 "Quit voluntarily" 1 "Serious adverse eventdue to rhabdomyolysis"
LOCAL ADVERSE EVENTS/SYSTEMIC ADVERSE EVENTS/ADVERSE EVENTS
Missingness could depend on the true value of the outcome.
Not likely that missingness depended on the true value of the outcome
Risk assessed to be some concerns for the outcomes: Local adverse events. Systemic adverse events.
WITHDRAWAL DUE TO ADVERSE EVENTS/SERIOUS ADVERSE EVENTS
Missingness could not depend on the true value of the outcome.
Risk assessed to be low for the outcomes: Withdrawal 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.
Comment: Blinded study (laboratory personnel, participants, investigators).
Risk assessed to be low for the outcomes: Local adverse events. Systemic adverse events. Withdrawal due to adverse events. Adverse events. Serious adverse events.
Selection of the reported results
Some concerns 		Comment: The protocol, statistical analysis plan and registry were available but retrospective.
No information on whether the result was selected from multiple outcome measurements or analyses of the data.
No information on whether the trial was analyzed as pre-specified.
Risk assessed to be some concerns for the outcomes: Local adverse events. Systemic adverse events. Adverse events. Withdrawal due to adverse events. Serious adverse events.
Overall risk of bias
Some concerns