Covid-19 Living Data

Trial ChiCTR2100051391
Publication Xia N, Research Square, 2023
Primary outcome on the report: Serious adverse events (SAE), medically attended adverse events (MAAE) and adverse events of special interest (AESI) from day 0 (after the first dose) through 12 months after the final dose; solicited adverse events (AE) for 7 days after each dose; and unsolicited adverse events for 30 days after each dose; Symptomatic COVID-19 confirmed by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) test occurring at least 14 days after the second dose in the per-protocol population (participants who were followed-up for at least two weeks after the second dose and had no major protocol deviatiations)

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:"Block randomization was performed based on each study centre using an interactive web-response system (IWRS) and stratified according to age (18 t 59 years or ≥60 years) and the presence or absence of a history of COVID-19 vaccination. The unblinded statistician from the contract research organization (CRO) who designed the randomization plan and generated the block randomization codes by SAS (version 9.4) was not involved in other work relevant to this trial." Quote:"Each participant was assigned a computer-generated randomization code, a unique investigational product code and a room code (A, D, K and Y) in order of enrolment, and assigned to the same treatment group for the second dose. The randomization code was always hidden during the trial, only the unblinded statistician could check it on the system. The room code could only be accessible to the designated investigators for a5 limited time and the documents involving the room code were sealed in a separate envelope after use, which further ensured masking." Comment: Allocation sequence random Allocation sequence probably concealed Imbalances in baseline characteristics appear to be compatible with chance
Deviations from intervention	Some concerns	Quote: “double blinding” Comment: Blinded study (participants and personnel/carers) CONFIRMED SYMPTOMATIC COVID-19 Per-protocol analysis was performed on the outcomes. Reasons for exclusion: received other COVID-19 vaccine less than 180 days before the first dose (1800 vs 1782); had COVID-19 within 14 days (26 vs 22); Follow up time less than 15 days (9 vs4); Did not meet the inlcusion criteria (5 vs 4); Met the exclusion criteria (52 vs 46); vaccination error (1 vs 2); did not received the second dose within the time-window (151 vs 151). 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 due to balance in the number of exclusions between arms. Risk assessed to be some concerns for the outcomes: Confirmed COVID-19. ADVERSE EVENTS. SERIOUS ADVERSE EVENTS Participants who received at least one dose of vaccine were included in the vaccine group 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 the outcomes: Adverse events. Serious adverse events.
Missing outcome data	Low	Comment: 17210 participants randomized; 17176 participants analyzed for the outcomes Adverse events and Serious adverse events; 12717 participants analyzed for the outcome Confirmed symptomatic ADVERSE EVENTS. SERIOUS ADVERSE EVENTS Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Adverse events. Serious adverse events. CONFIMED SYMPTOMATIC COVID-19 Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: protocol deviations. Risk of bias assessed on domain 2. Missingness could not depend on the true value of the outcome. Risk assessed to be low for the outcomes: Confirmed 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 COVID. Adverse events. Serious adverse events.
Selection of the reported results	Low	Comment: The trial registry was available (dated 2021-09-22). 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 COVID. Adverse events. Serious adverse events.
Overall risk of bias	Some concerns