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 and 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, and Edward P. Ficaro

43

5

Protein Biomarker Discovery Using Mass Spectrometry–Based Proteomics   Joanna M. Hunter and Daniel Chelsky

101

6

Quantitative Multiplexed Patterning of Immune-Related Biomarkers   Dominic Eisinger, Ralph McDade, and Thomas Joos

121

7

Gene Expression Profiles as Preclinical and Clinical Cancer Biomarkers of Prognosis, Drug Response, and Drug Toxicity   Jason A. Sprowl and 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, and 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, and 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 and 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 and 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 and 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

Translational 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, and 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, and Bruce McManus

375

20

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

399

21

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

413

22

Validating in Vitro Toxicity Biomarkers Against Clinical Endpoints   Culvert Louden and 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, and Deborah Elstein

475

26

Value Chain in the Development of Biomarkers for Disease Targets   Charles W. Richard, Hi, Arthur O. Tzianabos, and 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, and Nita Ichhpurani

495

28

Integrating Academic Laboratories into Pharmaceutical Development   Peter A. Ward and 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, and William R. Foster

541

31

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

551

32

Biomarker Patent Strategies: Opportunities and Risks   Cynthia M. Bott and Eric J. Baude

565

PART VIII

WHERE ARE WE HEADING AND WHAT DO WE REALLY NEED?

575

33

It Supporting Biomarker-Enabled Drug Development   Michael Hehenberger

577

34

Redefining Disease and Pharmaceutical Targets through Molecular Definitions and Personalized Medicine   Craig P. Webb, John F. Thompson, and 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, and 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 Gimona

693

38

Nanotechnology-Based Biomarker Detection   Joshua Reineke

709

Index

731