Table Of ContentStatistics
Clinical and Statistical Considerations in Personalized Medicine explores
recent advances related to biomarkers and their translation into clinical
development. Leading clinicians, biostatisticians, regulators, commercial
professionals, and researchers address the opportunities and challenges in
successfully applying biomarkers in drug discovery and preclinical and clinical
development.
Clinical and Statistical
The frst four chapters discuss biomarker development from a clinical
perspective. Coverage ranges from an introduction to biomarkers to advances
Considerations in
in RNAi screens, epigenetics, and rare diseases as targets for personalized
medicine approaches. Subsequent chapters examine the statistical
Personalized Medicine
considerations in applying a personalized medicine approach, including
multiplicity in pharmacogenomics. The last chapter assesses the regulatory
issues involved in using biomarkers.
Features
• Explores the rapidly expanding area of epigenetics and how it relates to
personalized medicine, including approaches targeted to rare diseases
• Addresses the statistical considerations in using biomarkers, such as the
control of false-positive rates due to multiple testing
• Covers new approaches in biomarker-informed adaptive design, an
adaptive dose-fnding design, and evidence-based adaptive decision and
design strategies in programs with predictive biomarkers
• Describes statistical methods for the identifcation of biomarkers in
clinical trials
• Discusses the importance of patient-report outcomes in personalized
medicine
• Presents case studies that illustrate regulatory issues
Despite the vast amount of literature on biomarkers, there is no comprehensive
book that integrates the clinical and statistical components. This book is one of
the frst to incorporate both the clinical and statistical aspects of biomarkers in
the personalized medicine paradigm. Covering a wide spectrum of personalized Edited by
medicine-related topics, it presents state-of-the-art techniques for advancing Claudio Carini
the application of biomarkers in drug discovery and development.
Sandeep Menon
Mark Chang
K20653
K20653_Cover.indd 1 2/27/14 10:53 AM
Clinical and Statistical Considerations
Carini, Menon, and Chang
in Personalized Medicine
Clinical and Statistical
Considerations in
Personalized Medicine
Editor-in-Chief
Shein-Chung Chow, Ph.D., Professor, Department of Biostatistics and Bioinformatics,
Duke University School of Medicine, Durham, North Carolina
Series Editors
Byron Jones, Biometrical Fellow, Statistical Methodology, Integrated Information Sciences,
Novartis Pharma AG, Basel, Switzerland
Jen-pei Liu, Professor, Division of Biometry, Department of Agronomy,
National Taiwan University, Taipei, Taiwan
Karl E. Peace, Georgia Cancer Coalition, Distinguished Cancer Scholar, Senior Research Scientist
and Professor of Biostatistics, Jiann-Ping Hsu College of Public Health,
Georgia Southern University, Statesboro, Georgia
Bruce W. Turnbull, Professor, School of Operations Research and Industrial Engineering,
Cornell University, Ithaca, New York
Published Titles
Adaptive Design Methods in Bayesian Missing Data Problems: EM,
Clinical Trials, Second Edition Data Augmentation and Noniterative
Shein-Chung Chow and Mark Chang Computation
Ming T. Tan, Guo-Liang Tian,
Adaptive Design Theory and
and Kai Wang Ng
Implementation Using SAS and R
Mark Chang Bayesian Modeling in Bioinformatics
Dipak K. Dey, Samiran Ghosh,
Advanced Bayesian Methods for Medical
and Bani K. Mallick
Test Accuracy
Lyle D. Broemeling Beneft-Risk Assessment in
Pharmaceutical Research and
Advances in Clinical Trial Biostatistics
Development
Nancy L. Geller
Andreas Sashegyi, James Felli, and
Applied Meta-Analysis with R
Rebecca Noel
Ding-Geng (Din) Chen and Karl E. Peace
Biosimilars: Design and Analysis of
Basic Statistics and Pharmaceutical
Follow-on Biologics
Statistical Applications, Second Edition
Shein-Chung Chow
James E. De Muth
Biostatistics: A Computing Approach
Bayesian Adaptive Methods for
Stewart J. Anderson
Clinical Trials
Causal Analysis in Biomedicine and
Scott M. Berry, Bradley P. Carlin,
Epidemiology: Based on Minimal
J. Jack Lee, and Peter Muller
Suffcient Causation
Bayesian Analysis Made Simple: An Excel
Mikel Aickin
GUI for WinBUGS
Clinical and Statistical Considerations
Phil Woodward
in Personalized Medicine
Bayesian Methods for Measures of
Claudio Carini, Sandeep Menon,
Agreement
and Mark Chang
Lyle D. Broemeling
Clinical Trial Data Analysis using R
Bayesian Methods in Epidemiology
Ding-Geng (Din) Chen and Karl E. Peace
Lyle D. Broemeling
Clinical Trial Methodology
Bayesian Methods in Health Economics
Karl E. Peace and Ding-Geng (Din) Chen
Gianluca Baio
Computational Methods in Biomedical Elementary Bayesian Biostatistics
Research Lemuel A. Moyé
Ravindra Khattree and Dayanand N. Naik
Frailty Models in Survival Analysis
Computational Pharmacokinetics Andreas Wienke
Anders Källén
Generalized Linear Models: A Bayesian
Confdence Intervals for Proportions and Perspective
Related Measures of Effect Size Dipak K. Dey, Sujit K. Ghosh,
Robert G. Newcombe and Bani K. Mallick
Controversial Statistical Issues in Handbook of Regression and Modeling:
Clinical Trials Applications for the Clinical and
Shein-Chung Chow Pharmaceutical Industries
Daryl S. Paulson
Data and Safety Monitoring Committees
in Clinical Trials Interval-Censored Time-to-Event Data:
Jay Herson Methods and Applications
Ding-Geng (Din) Chen, Jianguo Sun,
Design and Analysis of Animal Studies in
and Karl E. Peace
Pharmaceutical Development
Shein-Chung Chow and Jen-pei Liu Joint Models for Longitudinal and Time-
to-Event Data: With Applications in R
Design and Analysis of Bioavailability and
Dimitris Rizopoulos
Bioequivalence Studies, Third Edition
Shein-Chung Chow and Jen-pei Liu Measures of Interobserver Agreement
and Reliability, Second Edition
Design and Analysis of Bridging Studies
Mohamed M. Shoukri
Jen-pei Liu, Shein-Chung Chow,
and Chin-Fu Hsiao Medical Biostatistics, Third Edition
A. Indrayan
Design and Analysis of Clinical Trials with
Time-to-Event Endpoints Meta-Analysis in Medicine and Health
Karl E. Peace Policy
Dalene Stangl and Donald A. Berry
Design and Analysis of Non-Inferiority
Trials Monte Carlo Simulation for the
Mark D. Rothmann, Brian L. Wiens, Pharmaceutical Industry: Concepts,
and Ivan S. F. Chan Algorithms, and Case Studies
Mark Chang
Difference Equations with Public Health
Applications Multiple Testing Problems in
Lemuel A. Moyé and Asha Seth Kapadia Pharmaceutical Statistics
Alex Dmitrienko, Ajit C. Tamhane,
DNA Methylation Microarrays:
and Frank Bretz
Experimental Design and Statistical
Analysis Optimal Design for Nonlinear Response
Sun-Chong Wang and Arturas Petronis Models
Valerii V. Fedorov and Sergei L. Leonov
DNA Microarrays and Related Genomics
Techniques: Design, Analysis, and Patient-Reported Outcomes:
Interpretation of Experiments Measurement, Implementation and
David B. Allison, Grier P. Page, Interpretation
T. Mark Beasley, and Jode W. Edwards Joseph C. Cappelleri, Kelly H. Zou,
Andrew G. Bushmakin, Jose Ma. J. Alvir,
Dose Finding by the Continual
Demissie Alemayehu, and Tara Symonds
Reassessment Method
Ying Kuen Cheung
Randomized Clinical Trials of Statistical Methods for Clinical Trials
Nonpharmacological Treatments Mark X. Norleans
Isabelle Boutron, Philippe Ravaud, and
Statistics in Drug Research:
David Moher
Methodologies and Recent
Randomized Phase II Cancer Clinical Developments
Trials Shein-Chung Chow and Jun Shao
Sin-Ho Jung
Statistics in the Pharmaceutical Industry,
Sample Size Calculations in Clinical Third Edition
Research, Second Edition Ralph Buncher and Jia-Yeong Tsay
Shein-Chung Chow, Jun Shao
Survival Analysis in Medicine and
and Hansheng Wang
Genetics
Statistical Analysis of Human Growth Jialiang Li and Shuangge Ma
and Development
Theory of Drug Development
Yin Bun Cheung
Eric B. Holmgren
Statistical Design and Analysis of
Translational Medicine: Strategies and
Stability Studies
Statistical Methods
Shein-Chung Chow
Dennis Cosmatos and Shein-Chung Chow
Statistical Evaluation of Diagnostic
Performance: Topics in ROC Analysis
Kelly H. Zou, Aiyi Liu, Andriy Bandos,
Lucila Ohno-Machado, and Howard Rockette
Clinical and Statistical
Considerations in
Personalized Medicine
Edited by
Claudio Carini
Pfzer
Cambridge, Massachusetts, USA
Sandeep Menon
Pfzer
Cambridge, Massachusetts, USA
Mark Chang
AMAG Pharmaceuticals, Inc.
Waltham, Massachusetts, USA
CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
© 2014 by Taylor & Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Version Date: 20140127
International Standard Book Number-13: 978-1-4665-9387-9 (eBook - PDF)
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Contents
Preface ......................................................................................................................ix
Editors ......................................................................................................................xi
Contributors ...........................................................................................................xv
1. Biomarkers for Drug Development: The Time Is Now! .........................1
Claudio Carini and Attila Seyhan
2. RNAi Screens: Triumphs and Tribulations ............................................ 27
Attila Seyhan and Claudio Carini
3. Current Advances in Epigenetics .............................................................. 75
Ewan Hunter and Alexandre Akoulitchev
4. Biomarkers and Precision Medicine: The Case of Rare Diseases .... 117
Candida Fratazzi and Claudio Carini
5. Biomarker-Informed Adaptive Design .................................................. 129
Jing Wang, Mark Chang, and Sandeep Menon
6. Fitting the Dose: Adaptive Staggered Dose Design ............................ 149
Joseph Wu, Sandeep Menon, and Mark Chang
7. Evidence-Based Adaptive Statistical Decision and Design
Strategies for Maximizing the Effciency of Clinical Oncology
Development Programs with Predictive Biomarkers ......................... 179
Cong Chen and Robert A. Beckman
8. Biomarker Identifcation in Clinical Trials ........................................... 211
Ilya Lipkovich and Alex Dmitrienko
9. Multiplicity in Pharmacogenomics ......................................................... 265
Lingyun Liu, Fredrick Immermann, and Sandeep Menon
10. Patient-Reported Outcomes in Personalized Medicine...................... 297
Demissie Alemayehu and Joseph C. Cappelleri
11. Regulatory Issues in Use of Biomarkers in Drug Development ...... 313
Aloka G. Chakravarty
vii
