Sample size determination and statistical analysis
ADVERSE REACTIONS, -11
For the consistency assessment, equivalence is considered to be fulfilled when the 95% confidence interval (CI) for the inter-group GMT ratio were between 0.67 and 1.5, which was equivalent to the GMT difference after logGenerally, Pearson’s chi-squared test, Fisher’s exact test or one-way ordered Cochran–Mantel–Haenszel (CMH) test were applied to analyze categorical variables for group comparison, and analysis of variance (ANOVA) were used for continuous variables to compare the difference between groups. Observed GMTs and corresponding 95%CIs were calculated based on a standard normal distribution of logarithmic transformed GMT. The 95%CIs of seropositive rate and seroconversion rate were calculated using Clopper-Pearson analysis. For equivalence analysis, analysis of covariance (ANCOVA) model was applied, where the logarithmic transformed GMT 28 days after full course of vaccination was the dependent variable, vaccines groups (lots or workshops) were the fixed effects, and logarithmic transformed GMT before vaccination was the covariate. Adjusted GMT ratios and corresponding 95%CIs were then estimated by the geometric least-square mean from the ANCOVA model for the comparisons between each pair of groups (Lot 1/Lot 2, Lot 1/Lot 3, Lot 2/Lot 3, Workshop 1/Workshop 2, Workshop 1/Workshop 3, and Workshop 2/Workshop 3). When both sides of 95%CIs of GMT ratios fell into [0.67, 1.5], the consistency of the comparison groups was fulfilled.Subgroup analyses were also performed by age groups (3-5, 6-11 and 12-17 years) for neutralizing antibodies and incidence of adverse reactions. Exploratory analyses were applied to evaluate the antibodies response at 7 and 14 days after vaccination in the immunogenicity subgroup participants. Hypothesis testing was two-sided, and p values of less than 0.05 were considered to be significant. All analyses were conducted with SAS (Version 9.4, SAS Institute Inc., Cary, USA).