Biomarkers in Drug Development: A Handbook of Practice, Application, and Strategy Book

Contributors ix

Preface xv

Part I Biomarkers and Their Role in Drug Development 1

1 Biomarkers Are Not New Ian Dews 3

2 Biomarkers: Facing the Challenges at the Crossroads of Research and Health Care Gregory J. Downing 15

3 Enabling Go/No Go Decisions J. Fred Pritchard Mallé Jurima-Romet 31

Part II Identifying New Biomarkers: Technology Approaches 41

4 Imaging as a Localized Biomarker: Opportunities and Challenges Jonathan B. Moody Philip S. Murphy Edward P. Ficaro 43

5 Protein Biomarker Discovery Using Mass Spectrometry-Based Proteomics Joanna M. Hunter Daniel Chelsky 101

6 Quantitative Multiplexed Patterning of Immune-Related Biomarkers Dominic Eisinger Ralph McDade Thomas Joos 121

7 Gene Expression Profiles as Preclinical and Clinical Cancer Biomarkers of Prognosis, Drug Response, and Drug Toxicity Jason A. Sprowl Amadeo M. Parissenti 135

8 Use of High-Throughput Proteomic Arrays for the Discovery of Disease-Associated Molecules Douglas M. Molina W John W. Morrow Xiaowu Liang 155

Part III Characterization and Validation 177

9 Characterization and Validation Biomarkers in Drug Development: Regulatory Perspective Federico Goodsaid 179

10 Fit-for-Purpose Method Validation and Assays for Biomarker Characterization to Support Drug Development Jean W. Lee Yuling Wu Jin Wang 187

11 Molecular Biomarkers from a Diagnostic Perspective Klaus Lindpaintner 215

12 Strategies for the Co-Development of Drugs and Diagnostics: FDA Perspective on Diagnostics Regulation Francis Kalush Steven Gutman 231

13 Importance of Statistics in the Qualification and Application of Biomarkers Mary Zacour 247

Part IV Biomarkers in Discovery and Preclinical Safety 287

14 Qualification of Safety Biomarkers for Application to Early Drug Development William B. Mattes Frank D. Sistare 289

15 Development of Serum Calcium and Phosphorus as Clinical Biomarkers for Drug-Induced Systemic Mineralization: Case Study with a MEK Inhibitor Alan P. Brown 301

16 Biomarkers for the Immunogenicity of Therapeutic Proteins and Its Clinical Consequences Claire Cornips Huub Schellekens 323

17 New Markers of Kidney Injury Sven A. Beushausen 335

Part V Translating from Preclinical Results to Clinical and Back 359

18 Translation Medicine-A Paradigm Shift in Modern Drug Discovery and Development: The Role of Biomarkers Giora Z. Feuerstein Salvatore Alesci Frank L. Walsh J. Lynn Rutkowski Robert R. Ruffolo, Jr. 361

19 Clinical Validation and Biomarker Translation David Lin Andreas Scherer Raymond Ng Robert Balshaw Shawna Flynn Paul Keown Robert McMaster Bruce McManus 375

20 Predicting and Assessing an Inflammatory Disease and Its Complications: Example from Rheumatoid Arthritis Christina Trollmo Lars Klareskog 399

21 Pharmacokinetic and Pharmacodynamic Biomarker Correlations J.F. Marier Keith Gallicano 413

22 Validating In Vitro Toxicity Biomarkers Against Clinical Endpoints Calvert Louden Ruth A. Roberts 433

Part VI Biomarkers in Clinical Trials 443

23 Opportunities and Pitfalls Associated with Early Utilization of Biomarkers: Case Study in Anticoagulant Development Kay A. Criswell 445

24 Integrating Molecular Testing Into Clinical Applications Anthony A. Killeen 463

25 Biomarkers for Lysosomal Storage Disorders Ari Zimran Candida Fratazzi Deborah Elstein 475

26 Value Chain in the Development of Biomarkers for Disease Targets Charles W. Richard, III Arthur O. Tzianabos Whaijen Soo 485

Part VII Lessons Learned: Practical Aspects of Biomarker Implementation 493

27 Biomarkers in Pharmaceutical Development: The Essential Role of Project Management and Teamwork Lena King Mallé Jurima-Romet Nita Ichhpurani 495

28 Integrating Academic Laboratories into Pharmaceutical Development Peter A. Ward Kent J. Johnson 515

29 Funding Biomarker Research and Development Through the Small Business Innovative Research Program James Varani 527

30 Novel and Traditional Nonclinical Biomarker Utilization in the Estimation of Pharmaceutical Therapeutic Indices Bruce D. Car Brian Gemzik William R. Foster 541

31 Anti-Unicorn Principle: Appropriate Biomarkers Don't Need to Be Rare or Hard to Find Michael R. Bleavins Ramin Rahbari 551

32 Biomarker Patent Strategies: Opportunities and Risks Cynthia M. Bott Eric I Baude 565

Part VIII Where Are We Heading and What Do We Really Need? 575

33 IT Supporting Biomarker-Enabled Drug Development Michael Hehenberger 377

34 Redefining Disease and Pharmaceutical Targets Through Molecular Definitions and Personalized Medicine Craig P. Webb John F. Thompson Bruce H. Littman 593

35 Ethics of Biomarkers: The Borders of Investigative Research, informed Consent, and Patient Protection Heather Walmsley Michael Burgess Jacquelyn Brinkman Richard Hegele Janet Wilson-McManus Bruce McManus 625

36 Pathodynamics: Improving Biomarker Selection by Getting More Information from Changes Over Time Donald C. Trost 643

37 Optimizing the Use of Biomarkers for Drug Development: A Clinician's Perspective Alberto Gimnona 693

38 Nanotechnology-Based Biomarker Detection Joshua Reineke 709

Index 731