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

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