Biomarkers in Drug Discovery and Development. A Handbook of Practice, Application, and Strategy

List of Contributors ix

Preface

Part I Biomarkers and Their Role in Drug Development x

1 Biomarkers Are Not New x
Ian Dews

2 Biomarkers: Facing the Challenges at the Crossroads of Research and Health Care x
Gregory J. Downing

3 Enabling Go/No Go Decisions x
J. Fred Pritchard and M. Lynn Pritchard

4 Developing a Clinical Biomarker Method with External Resources: A Case Study x
Ross A. Fredenburg

Part II Biomarker Technologies x

5 Imaging as a Localized Biomarker: Opportunities and Challenges x
Jonathan B. Moody, Philip S. Murphy, and Edward P. Ficaro

6 Imaging for Early Clinical Drug Development: Integrating Imaging Science With Drug Research x
Philip S. Murphy, Mats Bergstrom, Jonathan B. Moody, and Edward P. Ficaro

7 Circulating microRNAs as Biomarkers in Cardiovascular and Pulmonary Vascular Disease: Promises and Challenges x
Miranda K. Culley and Stephen Y. Chan

Part III Characterization, Validation, and Utilization x

8 Characterization and Validation Biomarkers in Drug Development: Regulatory Perspective x
Federico Goodsaid

9 Fit-for-Purpose Method Validation and Assays of Protein Biomarkers During Drug Development x
Jean W. Lee, Yuling Wu, and Jin Wang

10 Applying Statistics Appropriately for Your Biomarker Application x
Mary Zacour

Part IV Biomarkers in Discovery and Preclinical Safety x

 

11 Qualification of Safety Biomarkers for Application to Early Drug Development x
William B. Mattes and Frank D. Sistare

12 A Pathologist’s View of Drug and Biomarker Development x
Robert W. Dunstan

13 Development of Serum Calcium and Phosphorus as Clinical Biomarkers for Drug-Induced Systemic Mineralization: Case Study with a MEK Inhibitor x
Alan P. Brown

14 New Markers of Kidney Injury x
Sven A. Beushausen

Part V Translating from Preclinical to Clinical and Back x

15 Biomarkers from Bench to Bedside and Back – Back Translation of Clinical Studies to Pre-clinical Models x
Damian O’Connell, Zaki Shaikhibrahim, Frank Kramer, and Matthias Ocker

16 Translational Medicine—A Paradigm Shift in Modern Drug Discovery and Development: The Role of Biomarkers x
Giora Z. Feuerstein, Salvatore Alesci, Frank L. Walsh, J. Lynn Rutkowski, and Robert R. Ruffolo, Jr.

17 Clinical Validation and Biomarker Translation x
Ji-Young V. Kim, Raymond T. Ng, Robert Balshaw, Paul Keown, Robert McMaster, Bruce McManus, Karen Lam, and Scott J. Tebbutt

18 Predicting and Assessing an Inflammatory Disease and Its Complications: Example from Rheumatoid Arthritis x
Christina Trollmo and Lars Klareskog

19 Validating In Vitro Toxicity Biomarkers Against Clinical Endpoints x
Calvert Louden and Ruth A. Roberts

Part VI Biomarkers in Clinical Trials x

 

20 Opportunities and Pitfalls Associated with Early Utilization of Biomarkers: Case Study in Anticoagulant Development x
Kay A. Criswell

21 Integrating Molecular Testing into Clinical Applications x
Anthony A. Killeen

Part VII Big Data, Data Mining and Biomarkers x

 

22 IT Supporting Biomarker Enabled Drug Development x
Michael Hehenberger

23 Identifying Biomarker Profiles Through the Epidemiologic Analysis of Big Healthcare Data Implications for Clinical Management and Clinical Trial Design: A Case Study in Anemia of Chronic Kidney Disease x
Gregory P. Fusco

24 Computational Biology Approaches to Support Biomarker Discovery and Development xq
Bin Li, Hyunjin Shin, William L. Trepiccho, and Andrew Dorner

Part VIII Lessons Learned: Practical Aspects of Biomarker Implementation X

 

25 Biomarkers in Pharmaceutical Development: The Essential Role of Project Management and Teamwork x
Lena King, Malle Jurima-Romet, and Nita Ichhpurani

26 Novel and Traditional Nonclinical Biomarker Utilization in the Estimation of Pharmaceutical Therapeutic Indices x
Bruce D. Car, Brian Gemzik, and William R. Foster

Part IX Where Are We Heading and What Do We Really Need? x

 

27 Ethics of Biomarkers: The Borders of Investigative Research, Informed Consent, and Patient Protection x
Sara Assadian, Michael Burgess, Breanne Crouch, Karen Lam, and Bruce McManus

28 Anti-Unicorn Principle: Appropriate Biomarkers Don’t Need to Be Rare or Hard to Find x
Michael R. Bleavins and Ramin Rahbari

29 Translational Biomarker Imaging: Applications, Trends and Successes Today and Tomorrow x
Patrick McConville and Deanne Lister

Index 

This book continues the legacy of a well-established reference within the pharmaceutical industry – providing perspective, covering recent developments in technologies that have enabled the expanded use of biomarkers, and discussing biomarker characterization and validation and applications throughout drug discovery and development.

• Explains where proper use of biomarkers can substantively impact drug development timelines and costs, enable selection of better compounds and reduce late stage attrition, and facilitate personalized medicine
• Helps readers get a better understanding of biomarkers and how to use them, for example which are accepted by regulators and which still non-validated and exploratory
• Updates developments in genomic sequencing, and application of large data sets into pre-clinical and clinical testing; and adds new material on data mining, economics, and decision making, personal genetic tools, and wearable monitoring
• Includes case studies of biomarkers that have helped and hindered decision making
• Reviews of the first edition: “If you are interested in biomarkers, and it is difficult to imagine anyone reading this who wouldn't be, then this book is for you." (ISSX) and “…provides a good introduction for those new to the area, and yet it can also serve as a detailed reference manual for those practically involved in biomarker implementation.” (ChemMedChem)

Ramin Rahbari, MS, is lead for biomarkers at Cognizant Technology System and has previously held similar positions at IBM and Innovative Scientific management.

Jonathan Van Niewaal, PhD is Information Systems Manager at Travelers Corporation and a software engineer who has worked with global clients in the healthcare, financial services, and technology industries.

Michael R. Bleavins, PhD, is the founder of White Crow Innovation, LLC, a Michigan-based drug development consulting company, and cofounder of Michigan Technology and Research Institute.