A Threshold Regression Mixture Model for Assessing Treatment Efficacy in a Multiple Myeloma Clinical Trial

Details

• Personal Author:
  Chang M ; Lee M-LT ; Whitmore GA
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Mortality Occupational Health Safety
• Keywords:
  Analytical-methods Analytical-models Analytical-processes Mathematical-models Mortality-surveys Statistical-analysis Therapeutic-agents Treatment
• ISSN:
  1054-3406
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; Massachusetts ; OSHA Region 1 ; OSHA Region 3
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  18
• Issue:
  6
• NIOSHTIC Number:
  nn:20034699
• Citation:
  J Biopharm Stat 2008 Nov; 18(6):1136-1149
• Contact Point Address:
  Mei-Ling Ting Lee, Department of Epidemiology and Biostatistics, School of Public Health, University of Maryland, College Park, MD 20740, USA
• Email:
  mltlee@umd.edu
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Transportation, Warehousing and Utilities
• Performing Organization:
  University of Maryland - College Park
• Peer Reviewed:
  True
• Start Date:
  20060901
• Source Full Name:
  Journal of Biopharmaceutical Statistics
• End Date:
  20090831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e1ca216412142954b32f4aef734957faf51d1f0078eea1c72c22d1bbf279abddb4cd10a9efbb6a11a07bcb8873a68ec8c1ada451188fd83b22ef986acd74686a
• Download URL:
  https://stacks.cdc.gov/view/cdc/186810/cdc_186810_DS1.pdf
• File Type:
  [PDF - 337.53 KB ]