Pharmacogenomics: Delivering on the Promise

Published by	Insight Pharma Reports
Published	June, 2009	Product code	92511
Content info	184 pages
Price	US $ 3195 PDF by E-mail ( Single User License) US $ 3995 PDF by E-mail (Single Site License) US $ 9950 PDF by E-mail ( Single User License)

Introduction
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Pharmacogenomics: Delivering on the Promise published by Insight Pharma Reports in June, 2009. This report consists of 184 pages and the price starts from US $ 3195.

Introduction

Abstract

Pharmacogenomics (PGx) is often considered "the great new wave" in medicine, promising better, safer, and more affordable healthcare. Yet its adoption and widespread use in the clinic is up against some tremendous challenges. This report considers:

Drivers of PGx
Applications of PGx in drug development
Industry experiences with PGx and lessons learned
Type of evidence needed to establish clinical utility
Challenges to moving PGx forward
Survey results and expert views on utilization of PGx

Pharmacogenomics: Delivering on the Promise explores the pharmacogenomic (PGx) realm of personalized medicine, analyzing current R&D and market trends related to the use of genetic information to predict how well patients will respond to certain drugs. Pharmacogenomics is an extremely difficult business, one for which there are no easy answers. Even companies manufacturing and marketing already successful pharmacogenomic drug-test combinations continue to face difficulties. This report examines how these and other companies have (or are) navigating through the scientific, statistical/experimental design, and "clinical utility" landscape of PGx.

Not the least of the challenges facing pharmacogenomics is scientific. Separating a consistent, predictive association between a SNP or other genetic marker and a drug response phenotype from all the other variables that play into drug response can be next to impossible. Once candidate associations are identified, knowing how to design clinical trials capable of teasing out these associations in the clinic and aligning those trials in preparation for regulatory review create another set of challenges. Pharmacogenomics: Delivering on the Promise considers prospective versus retrospective clinical trial design and when, if ever, the FDA might allow the latter for regulatory decision-making purposes.

Moreover, validating an association in a carefully controlled clinical setting is different than knowing whether or not that association is truly clinically useful. The risk of a product not being adopted as the standard of care (either by prescribers, payers, or patients) because of insufficient evidence regarding its "clinical utility" is clearly a disincentive. Varying opinions raise questions about the nature of the evidence necessary for establishing the clinical utility of PGx tests. We consider the growing skepticism about the universal nature of the randomized controlled trial (RCT) gold standard and the usefulness of non-RCT experimental designs with respect to genetic testing.

Challenges examined include economic, reimbursement, regulatory, technological, and those related to a lack of physician education and awareness of pharmacogenetic testing. Overcoming these challenges could enable physicians to engage in smart PGx prescribing, leading to increased efficacy and reduced adverse drug reactions. PGx also has important applications in drug development, both with new drugs or new indications and as a way to "rescue" failed drugs; these various uses of PGx are explored in detail. Pharmacogenomics: Delivering on the Promise also includes comprehensive interviews with experts in the field and results from a qualitative survey of individuals involved with pharmacogenomics.

Chapter 1 PHARMACOGENOMICS TODAY: 21ST CENTURY PERSONALIZED MEDICINE

1.1. Introduction
- Pharmacogenomics: The Focus of This Report
- The Information in This Report
- The Concept of Pharmacogenomics
- Definition of Pharmacogenomics
- History of the Terms "Pharmacogenetics" and "Pharmacogenomics"
1.2. The Promise of Pharmacogenomics
- What Making Better Drugs Means
1.3. What Is Driving Pharmacogenomics?
- Money
- Dismal Effectiveness of Many of Today' s Common Drugs
- The Adverse Event Story: Safety Issues and Adverse Drug Reactions
- Public Policy
- The Science of Human Genetics
- Genome-Wide Association Studies and the Genetics of Human Disease
- Genome-Wide Association Studies and Drug Response

Chapter 2 PHARMACOGENOMICS IN THE MARKETPLACE: LESSONS LEARNED, UNANSWERED QUESTIONS

2.1. Introduction
2.2. Direct-To-Consumer Genetic Testing (Optimism): Its "Fun Factor" Is Driving Interest in Pharmacogenomics
- 23andMe: Direct-To-Consumer Genetic Testing and More
2.3. Warfarin: Optimism with Questions
- The Science Behind Warfarin Dosing: Still Building the Evidence Base
- Questions About Clinical Utility, Again
2.4. Herceptin: Even Successful Pharmacogenomic Products Have Generated Questions
- The Bigger Picture: What Is Evidence? What Is Value?
2.5. More on Evidence, Value, Clinical Utility... And What It All Means for Regulatory Decision-Making
- Clinical Utility Defined: It' s All About the Evidence...But What Type of Evidence?
- Assessing the Clinical Utility of PSA Screening: Do the Benefits Outweigh the Risks?
- The Randomized Controlled Trial Paradigm: Is It Necessary for Predictive Genetic Tests?
2.6. If Not Randomized Controlled Trials, Then What?
- The Medco-Mayo Study
- Calls From The Peer-Reviewed Literature Echo These Concerns About Randomized Controlled Trials
2.7. What To Do With All the Data
- The Notion of a National Genetic Test Registry
- Other Genetic Test Database Initiatives

Chapter 3 FROM CONCEPTUALIZING TO APPLYING PHARMACOGENOMICS: JUST DO IT

3.1. Introduction
3.2. Pharmacogenomics Is Not the Next Great Wave...It Is Already Here
- Pharmacogenomic Information in FDA-Approved Drug Labels
3.3. The "Google" (i.e., "Overly Optimistic") View of Applying Pharmacogenomics During Drug Development
3.4. The Reality of Utilizing a Pharmacogenomics-Based Approach During Drug Development
- Ways to Utilize Pharmacogenomics, or Pharmacogenetics, During Drug Development
- Efficacy Pharmacogenomics: GlaxoSmithKline and Rosiglitazone
- Safety Pharmacogenomics: GlaxoSmithKline and Abacavir
- The Beginning of a Trend?
3.5. Rescuing Failed Drugs vs. Rummaging Through the Trash: A Fine Line?
3.6. Utilizing Pharmacogenomics to Seize Missed Opportunities: CETP Inhibitors as a Case Study
- Pharmacogenomics and Statins

Chapter 4 THE FUTURE OF PHARMACOGENOMICS

4.1. Introduction
4.2. Economic Challenges: Is the Blockbuster Model Busting?
- Can Pharmacogenomics Really Save Companies Money?
4.3. Reimbursement
4.4. Regulatory Oversight
4.5. Physician Education
4.6. Impact of Technology on Pharmacogenomics
- Advances in DNA Sequencing
- Other Technologies That Could Potentially Advance Pharmacogenomics
- Nanotechnology and Pharmacogenomics
- Epigenetics and Drug Response
4.7. From Oncology Onward
- Pharmacogenomics in Psychiatry
- Iloperidone: A Long Road to Success
4.8. Concluding Remarks

Chapter 5 EXPERT INTERVIEWS

5.1. Information Technology and Pharmacogenomics: Challenges and Opportunities
- Interview with Teri E. Klein, PhD
- Senior Scientist, Stanford University
- Director, PharmGKB, Palo Alto, CA
5.2. A Perspective on Pharmacogenomics Based on Interviews With 60 Industry Executives and Key Opinion Leaders
- Interview with Philip Ma, PhD
- Director
- McKinsey & Company
- Palo Alto, CA
5.3. Planning Prospective Trials, Pipeline Management: Two Keys to Pharmacogenetic Success
- Interview with Allen D. Roses, MD
- Director, Deane Drug Discovery Institute, Duke University School of Medicine
- Jefferson-Pilot Professor of Neurobiology and Genetics, Duke University
- CEO, Cabernet Pharmaceuticals
- Durham, NC
5.4. Thoughts From Academia: From Functional Biomarkers to Healthcare Reform
- Interview with Wolfgang Sadee, PhD
- Professor and Chair, Pharmacology
- The Ohio State Medical Center
- Columbus, OH
5.5. Thoughts From a Statistician: Designing Pharmacogenetic Clinical Trials
- Interview with Richard Simon, DSc
- Chief, Biometric Research Branch
- Division of Cancer Treatment and Diagnosis
- National Cancer Institute
- Rockville, MD