title: A threshold regression mixture model for assessing treatment efficacy in a multiple myeloma clinical trial.
abstract: A first-hitting-time (FHT) survival model postulates a health status process for a patient that gradually declines until the patient dies when the level first reaches a critical threshold. Threshold regression (TR) is a new regression methodology that incorporates the effects of covariates on the threshold and process parameters of this FHT model. In this study, we use TR to analyze data from a randomized clinical trial of treatment for multiple myeloma. The trial compares VELCADE and high-dose dexamethasone, the former a new therapy and the latter an established therapy for this disease. Patients are switched between the two drugs based on patient response. The novel contribution of this work is the modeling of this clinical trial design using a mixture of TR models. Specifically, we propose a mixture FHT model to fit the survival distribution. The model includes a composite time scale that differentiates the rate of disease progression before and after switching. The analysis shows significant benefit from initial treatment by VELCADE. A comparison is made with a Cox proportional hazards regression analysis of the same data.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, University of Maryland, College Park, Maryland, USA.
authors.forename: Mei-Ling Ting
authors.initials: ML
authors.lastname: Lee
authors.forename: Mark
authors.initials: M
authors.lastname: Chang
authors.forename: G A
authors.initials: GA
authors.lastname: Whitmore
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D003627:Data Interpretation, Statistical; D003907:Dexamethasone / Q000627:therapeutic use*; D006305:Health Status Indicators; D006801:Humans; D016013:Likelihood Functions; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D016016:Proportional Hazards Models; D011719:Pyrazines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D018570:Risk Assessment; D013269:Stochastic Processes; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone