title: Inference of median difference based on the Box-Cox model in randomized clinical trials.
abstract: In randomized clinical trials, many medical and biological measurements are not normally distributed and are often skewed. The Box-Cox transformation is a powerful procedure for comparing two treatment groups for skewed continuous variables in terms of a statistical test. However, it is difficult to directly estimate and interpret the location difference between the two groups on the original scale of the measurement. We propose a helpful method that infers the difference of the treatment effect on the original scale in a more easily interpretable form. We also provide statistical analysis packages that consistently include an estimate of the treatment effect, covariance adjustments, standard errors, and statistical hypothesis tests. The simulation study that focuses on randomized parallel group clinical trials with two treatment groups indicates that the performance of the proposed method is equivalent to or better than that of the existing non-parametric approaches in terms of the type-I error rate and power. We illustrate our method with cluster of differentiation 4 data in an acquired immune deficiency syndrome clinical trial.
authors.affiliation: Clinical Data Science Department, Kowa Company, Ltd., Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Maruo
authors.forename: N
authors.initials: N
authors.lastname: Isogawa
authors.forename: M
authors.initials: M
authors.lastname: Gosho
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D000704:Analysis of Variance; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016014:Linear Models; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*
chemical_list: D054303:HIV Reverse Transcriptase
keywords: covariate adjustment; delta method; power-normal distribution