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<p>List of Contributors vii</p> <p>Preface xiii</p> <p><b>Part I Biomarkers and Their Role in Drug Development </b><b>1</b></p> <p>1 Biomarkers are Not New 3<br /><i>Ian Dews</i></p> <p>2 Biomarkers: Facing the Challenges at the Crossroads of Research and Health Care 15<br /><i>Gregory J. Downing</i></p> <p>3 Enabling Go/No Go Decisions 31<br /><i>J. Fred Pritchard and M. Lynn Pritchard</i></p> <p>4 Developing a Clinical Biomarker Method with External Resources: A Case Study 43<br /><i>Ross A. Fredenburg</i></p> <p><b>Part II Identifying New Biomarkers: Technology Approaches </b><b>51</b></p> <p>5 Imaging as a Localized Biomarker: Opportunities and Challenges 53<br /><i>Jonathan B. Moody, Philip S. Murphy, and Edward P. Ficaro</i></p> <p>6 Imaging for Early Clinical Drug Development: Integrating Imaging Science with Drug Research 89<br /><i>Philip S. Murphy, Mats Bergstrom, Jonathan B. Moody, and Edward P. Ficaro</i></p> <p>7 Circulating MicroRNAs as Biomarkers in Cardiovascular and Pulmonary Vascular Disease: Promises and Challenges 113<br /><i>Miranda K. Culley and Stephen Y. Chan</i></p> <p><b>Part III Characterization, Validation, and Utilization </b><b>139</b></p> <p>8 Characterization and Validation of Biomarkers in Drug Development: Regulatory Perspective 141<br /><i>Federico Goodsaid</i></p> <p>9 Fit-for-Purpose Method Validation and Assays for Biomarker Characterization to Support Drug Development 149<br /><i>Jean W. Lee, Yuling Wu, and Jin Wang</i></p> <p>10 Applying Statistics Appropriately for Your Biomarker Application 177<br /><i>Mary Zacour</i></p> <p><b>Part IV Biomarkers in Discovery and Preclinical Safety </b><b>219</b></p> <p>11 Qualification of Safety Biomarkers for Application to Early Drug Development 221<br /><i>William B. Mattes and Frank D. Sistare</i></p> <p>12 A Pathologist’s View of Drug and Biomarker Development 233<br /><i>Robert W. Dunstan</i></p> <p>13 Development of Serum Calcium and Phosphorus as Safety Biomarkers for Drug-Induced Systemic Mineralization: Case Study with the MEK Inhibitor PD0325901 255<br /><i>Alan P. Brown</i></p> <p>14 New Markers of Kidney Injury 281<br /><i>Sven A. Beushausen</i></p> <p><b>Part V Translating from Preclinical to Clinical and Back 307</b></p> <p>15 Biomarkers from Bench to Bedside and Back – Back-Translation of Clinical Studies to Preclinical Models 309<br /><i>Damian O'Connell, David Adler, Frank Kramer, and Matthias Ocker</i></p> <p>16 Translational Medicine – A Paradigm Shift in Modern Drug Discovery and Development: The Role of Biomarkers 333<br /><i>Giora Z. Feuerstein, Salvatore Alesci, Frank L.Walsh, J. Lynn Rutkowski, and Robert R. Ruffolo Jr.</i></p> <p>17 Clinical Validation and Biomarker Translation 347<br /><i>Ji-Young V. Kim, Raymond T. Ng, Robert Balshaw, Paul Keown, Robert McMaster, Bruce McManus, Karen Lam, and Scott J. Tebbutt</i></p> <p>18 Predicting and Assessing an Inflammatory Disease and Its Complications: Example from Rheumatoid Arthritis 365<br /><i>Christina Trollmo and Lars Klareskog</i></p> <p>19 Validating <i>In Vitro </i>Toxicity Biomarkers Against Clinical Endpoints 379<br /><i>Calvert Louden and Ruth A. Roberts</i></p> <p><b>Part VI Biomarkers in Clinical Trials 389</b></p> <p>20 Opportunities and Pitfalls Associated with Early Utilization of Biomarkers: A Case Study in Anticoagulant Development 391<br /><i>Kay A. Criswell</i></p> <p>21 Integrating Molecular Testing into Clinical Applications 409<br /><i>Anthony A. Killeen</i></p> <p><b>Part VII Big Data, Data Mining, and Biomarkers 421</b></p> <p>22 IT Supporting Biomarker-Enabled Drug Development 423<br /><i>Michael Hehenberger</i></p> <p>23 Identifying Biomarker Profiles Through the Epidemiologic Analysis of Big Health Care Data – Implications for Clinical Management and Clinical Trial Design: A Case Study in Anemia of Chronic Kidney Disease 447<br /><i>Gregory P. Fusco</i></p> <p>24 Computational Biology Approaches to Support Biomarker Discovery and Development 469<br /><i>Bin Li, Hyunjin Shin, William L. Trepicchio, and Andrew Dorner</i></p> <p><b>Part VIII Lessons Learned: Practical Aspects of Biomarker Implementation 485</b></p> <p>25 Biomarkers in Pharmaceutical Development: The Essential Role of Project Management and Teamwork 487<br /><i>Lena King, Mallé Jurima-Romet, and Nita Ichhpurani</i></p> <p>26 Novel and Traditional Nonclinical Biomarker Utilization in the Estimation of Pharmaceutical Therapeutic Indices 505<br /><i>Bruce D. Car, Brian Gemzik, and William R. Foster</i></p> <p><b>Part IX Where are We Heading and What Do We Really Need? 515</b></p> <p>27 Ethics of Biomarkers: The Borders of Investigative Research, Informed Consent, and Patient Protection 517<br /><i>Sara Assadian, Michael Burgess, Breanne Crouch, Karen Lam, and Bruce </i><i>McManus</i></p> <p>28 Anti-Unicorn Principle: Appropriate Biomarkers Don't Need to Be Rare or Hard to Find 537<br /><i>Michael R. Bleavins and Ramin Rahbari</i></p> <p>29 Translational Biomarker Imaging: Applications, Trends, and Successes Today and Tomorrow 553<br /><i>Patrick McConville and Deanne Lister</i></p> <p>Index 585</p>

<p><b>RAMIN RAHBARI, MS, MBA,</b> is an expert in biomarkers at Innovative Scientific Management and has previously held similar consulting and research positions at IBM, Cognizant and Pfizer. <p><b>JONATHAN VAN NIEWAAL, MBA,</b> is Technology Principal at Innovative Scientific Management and has held software development and technology delivery roles in the healthcare, financial services, and technology industries. <p><b>MICHAEL R. BLEAVINS, P<small>H</small>D, DABT,</b> is the founder of White Crow Innovation, LLC, a Michigan-based drug development consulting company, and cofounder of Michigan Technology and Research Institute.

<p><b>Reviews of the first edition:</b> <p><b>"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)</b> <p><b>"…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)</b> <p>As pharmaceutical companies struggle to improve the success rate and cost-effectiveness of the drug development process, biomarkers have emerged as a valuable tool. Continuing the legacy of a well-established pharmaceutical industry reference, the second edition of <i>Biomarkers in Drug Discovery and Development</i> provides perspective, covers recent technological developments, and discusses biomarker characterization and validation. <p>The chapters overview the areas where proper use of biomarkers can substantively impact drug development timelines and costs, enable the selection of better compounds, reduce late stage attrition, and facilitate personalized medicine. Contributing authors from the frontlines of industrial research and development present case studies of biomarkers that have helped and hindered decision making. The new edition updates existing information with developments in genomic sequencing and application of large data sets into pre-clinical and clinical testing; and introduces substantial new materials on data mining, economics, and decision making. <p>With such significant expansion and revision, <i>Biomarkers in Drug Discovery and Development, Second Edition</i> remains a key resource for biotechnology and major pharmaceutical companies, and their efforts to improve and expedite drug development.

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