title: Interpretable inference on the mixed effect model with the Box-Cox transformation.
abstract: We derived results for inference on parameters of the marginal model of the mixed effect model with the Box-Cox transformation based on the asymptotic theory approach. We also provided a robust variance estimator of the maximum likelihood estimator of the parameters of this model in consideration of the model misspecifications. Using these results, we developed an inference procedure for the difference of the model median between treatment groups at the specified occasion in the context of mixed effects models for repeated measures analysis for randomized clinical trials, which provided interpretable estimates of the treatment effect. From simulation studies, it was shown that our proposed method controlled type I error of the statistical test for the model median difference in almost all the situations and had moderate or high performance for power compared with the existing methods. We illustrated our method with cluster of differentiation 4 (CD4) data in an AIDS clinical trial, where the interpretability of the analysis results based on our proposed method is demonstrated. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: K
authors.identifier: 0000-0002-3093-0386
authors.initials: K
authors.lastname: Maruo
authors.affiliation: Japan-Asia Data Science, Development, Astellas Pharma Inc., Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Data Science, The Institute of Statistical Mathematics, Tokyo, Japan.
authors.forename: H
authors.identifier: 0000-0002-2520-9949
authors.initials: H
authors.lastname: Noma
authors.affiliation: Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Gosho
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology; D019380:Anti-HIV Agents / Q000008:administration & dosage; D056808:Biostatistics; D018791:CD4 Lymphocyte Count; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D004359:Drug Therapy, Combination; D006801:Humans; D016013:Likelihood Functions; D008137:Longitudinal Studies; D015233:Models, Statistical; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D018401:Sample Size
chemical_list: D019380:Anti-HIV Agents
keywords: Asymptotics; MMRM; longitudinal data; missingness; model misspecification