Statistical Methods

Descriptive statistics were applied, reported as numbers and percentages for categorical variables and as means with SD for continuous variables. Between-group data were compared using the independent t-test, the Chi-square, or the Fisher exact test. The non-parametric data were presented as median (interquartile range, IQR) using the Mann–Whitney U-test or Friedman test as appropriate. The statistical analysis followed both the modified intention-to-treat (mITT) and the per-protocol (PP) approach.³⁹ Missing values were imputed using the last observation carried forward method.

Reporting followed the CONSORT extension statement for non-inferiority trials.³¹ Non-inferiority at α is 0.025 in the one-tailed t-test, and the lower limit of the 95% confidence interval (CI) of the difference was within the presupposed non-inferiority margin only performed for the primary outcome measures. If the non-inferiority evidence rejects the null hypothesis, a superiority test would be conducted following the principle of sequential testing. The repeated measurement data of secondary outcome measures were analyzed using Generalized Estimating Equations (GEE), adjusted for age, sex, and the wCST-LL group. The overall alpha was 0.025 for both non-inferiority and superiority testing. The power calculation was performed using a non-inferiority test of the difference of two means in PASS 11. Data analysis was performed using SPSS V.26.0 (IBM Corporation, US) and NCSS V.12.0.

No interim analyses were planned or performed. Subgroups of wCST-LL, age, and other indicators were compared in a post hoc analysis (beyond the scope of the present study).