Dmitrienko / Tamhane / Bretz Multiple Testing Problems in Pharmaceutical Statistics

1. Auflage 2010
ISBN: 978-1-58488-985-4
Verlag: Taylor & Francis
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 320 Seiten

Reihe: Chapman & Hall/CRC Biostatistics Series

Useful Statistical Approaches for Addressing Multiplicity Issues
Includes practical examples from recent trials
Bringing together leading statisticians, scientists, and clinicians from the pharmaceutical industry, academia, and regulatory agencies, Multiple Testing Problems in Pharmaceutical Statistics explores the rapidly growing area of multiple comparison research with an emphasis on pharmaceutical applications. In each chapter, the expert contributors describe important multiplicity problems encountered in pre-clinical and clinical trial settings.

The book begins with a broad introduction from a regulatory perspective to different types of multiplicity problems that commonly arise in confirmatory controlled clinical trials, before giving an overview of the concepts, principles, and procedures of multiple testing. It then presents statistical methods for analyzing clinical dose response studies that compare several dose levels with a control as well as statistical methods for analyzing multiple endpoints in clinical trials. After covering gatekeeping procedures for testing hierarchically ordered hypotheses, the book discusses statistical approaches for the design and analysis of adaptive designs and related confirmatory hypothesis testing problems. The final chapter focuses on the design of pharmacogenomic studies based on established statistical principles. It also describes the analysis of data collected in these studies, taking into account the numerous multiplicity issues that occur.

This volume explains how to solve critical issues in multiple testing encountered in pre-clinical and clinical trial applications. It presents the necessary statistical methodology, along with examples and software code to show how to use the methods in practice.

Zielgruppe

Researchers, biostatisticians, and biometricians in drug discovery, pre-clinical, and clinical trials; graduate students in statistics, biostatistics, or public health.

Autoren/Hrsg.

Dmitrienko, Alex

Tamhane, Ajit C.

Bretz, Frank

Fachgebiete

• Technische Wissenschaften Verfahrenstechnik | Chemieingenieurwesen | Biotechnologie Pharmazeutische Technologie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Medizinische Fachgebiete Pharmakologie, Toxikologie
• Naturwissenschaften Biowissenschaften Botanik

Inhaltsverzeichnis

Multiplicity Problems in Clinical Trials: A Regulatory Perspective, Mohammad Huque and Joachim Röhmel
Introduction
Common multiplicity problems in clinical trials
Reducing multiplicity in clinical trials
Multiplicity concerns in special situations
Multiplicity in the analysis of safety endpoints
Concluding remarks
Multiple Testing Methodology, Alex Dmitrienko, Frank Bretz, Peter H. Westfall, James Troendle, Brian L. Wiens, Ajit C. Tamhane, and Jason C. Hsu
Introduction
Error rate definitions
Multiple testing principles
Adjusted significance levels, p-values, and confidence intervals
Common multiple testing procedures
Multiple testing procedures based on univariate p-values
Parametric multiple testing procedures
Resampling-based multiple testing procedures
Software implementation
Multiple Testing in Dose Response Problems, Frank Bretz, Ajit C. Tamhane, and José Pinheiro
Introduction
Dose response trend tests
Target dose estimation using multiple hypothesis testing
Power and sample size calculation for target dose estimation
Hybrid approaches combining multiple testing and modeling

Analysis of Multiple Endpoints in Clinical Trials, Ajit C. Tamhane and Alex Dmitrienko
Introduction
Inferential goals
At-least-one procedures
Global testing procedures
All-or-none procedures
Superiority-noninferiority procedures
Software implementation

Gatekeeping Procedures in Clinical Trials, Alex Dmitrienko and Ajit C. Tamhane
Introduction
Motivating examples
Serial gatekeeping procedures
Parallel gatekeeping procedures
Tree gatekeeping procedures
Software implementation

Adaptive Designs and Confirmatory Hypothesis Testing, Willi Maurer, Michael Branson, and Martin Posch
Introduction
Basic principles and methods of error rate control
Principles of adaptive testing procedures
Adaptive multiple testing procedures
Case studies
Discussion
Design and Analysis of Microarray Experiments for Pharmacogenomics, Jason C. Hsu, Youlan Rao, Yoonkyung Lee, Jane Chang, Kristin Bergsteinsdottir, Magnus Karl Magnússon, Tao Wang, and Eirikur Steingrímsson
Potential uses of biomarkers
Clinical uses of genetic profiling
Two stages of pharmacogenomic development
Multiplicity in pharmacogenomics
Designing pharmacogenomic studies
Analyzing microarray data by modeling
A proof of concept experiment
Software implementation

Bibliography

Über Autor(innen)

Alex Dmitrienko is a research advisor in Global Statistical Sciences at Eli Lilly and Company in Indianapolis, Indiana.
Ajit C. Tamhane is senior associate dean and professor of industrial engineering and management sciences in the McCormick School of Engineering and Applied Science at Northwestern University in Illinois.
Frank Bretz is a biometrical fellow of clinical information sciences at Novartis Pharma AG in Switzerland. He is also an adjunct professor at Hannover Medical School in Germany.