藥品開發第II期失敗率降低對策 是由出版商Insight Pharma Reports在2009年05月所出版的。
這份英文市場調查報告書包含160 pages 價格從美金3195起跳。
Abstract
Phase II is the critical development stage in which most clinical attrition
occurs. This report focuses on approaches to improving R&D productivity in the
pharmaceutical and biotechnology industries and considers:
Leading-edge strategies being pursued to improve success rates of therapeutic
candidates in clinical development The use of translational medicine studies
and early clinical trial protocols designed to reduce Phase II attrition
Survey results and expert interviews on efforts to improve R&D efficiency.
Pharmaceutical companies have been responding to a combination of major
challenges that many commentators call a "perfect storm." It is clear that the
high rate of attrition in the drug development process is severely limiting
the numbers of high-quality novel drug candidates, especially for innovative
drugs that address unmet medical needs. In order to overcome this limitation,
the industry must develop strategies that can reduce attrition during Phase
II, where most attrition occurs, especially as it continues to drive up the
cost of R&D to unsustainable levels.
Approaches to Reducing Phase II Attrition considers examples of leading-edge
strategies being pursued to improve target selection and other aspects of drug
discovery. These include development of multitargeted therapies, whole-pathway
approaches, biology-driven drug discovery, analysis of multigenic complex
diseases, and network pharmacology. Strategies for improving early-stage
clinical studies are discussed, including the use of Phase 0 and adaptive
trials, and employing early proof-of-concept trials. Ways in which some
companies have adopted new corporate structures designed to increase
innovation or make R&D more "biotech-like" are described.
Poorly predictive animal models constitute a major cause of drug attrition. We
present two case studies in CNS and cancer, two therapeutic areas in which
animal models are notorious for being poorly predictive. The CNS case study
focuses on attempts to improve animal model efficacy studies, and the cancer
case study focuses on industry' s adoption of improved animal models developed
in academia. In these discussions, we indicate how these particular case
studies may have lessons for efficacy studies in most therapeutic areas.
Well-designed translational studies may enable drugs that do not work in
humans to fail early. We examine various aspects of translational studies,
including definition of responder versus non-responder populations, and
optimal dosing regimens; and identification of early and sensitive markers of
efficacy, and of those patients who are likely to experience adverse effects.
Examples of ways in which translational medicine is changing the organization
of clinical trials in some companies are discussed. We also study the roles
that various types of biomarkers play in translational medicine, as well as
the current state of biomarker science. Case studies on stratification
biomarkers in cancer are presented.
Approaches to Reducing Phase II Attrition analyzes results from a survey of
current practices and views toward improving the efficiency and effectiveness
of drug development. Finally, the complete transcripts of interviews conducted
with experts in the field are provided.
Table of Contents
Chapter 1
- INTRODUCTION: CHALLENGES TO DRUG DEVELOPMENT TODAY
- 1.1. Responding to Industry Challenges by Corporate Restructuring
- 1.2. Responding to Industry Challenges by Large-Scale Mergers and
Acquisitions
- 1.3. Attrition in Drug Development
- The Kola and Landis Paper on Drug Attrition, 2004
- Drug Approvals, R&D Costs, and Attrition Rates Since 2003
- Strategies for Attacking the Phase II Attrition Problem
Chapter 2
- DRUG DISCOVERY STRATEGIES AIMED AT REDUCING PHASE II ATTRITION
- 2.1. Summary of the Target Evaluation Process
- 2.2. Strategies for Moving Beyond the Target Validation Paradigm
- Developing Agents That Address Multiple Targets
- Whole-Pathway Approaches to Drug Discovery
- Biology-Driven Drug Discovery
- Other Means of Going Beyond the Target Validation Paradigm
- 2.3. Target Generation at Pfizer' s Biotherapeutics & Bioinnovation Center
- 2.4. Novartis' Pathway-Based Drug Discovery Strategy
- 2.5. Genomic Analysis of Multiple Genes, Pathways, and Networks Involved
in Complex Diseases
- 2.6. Network Pharmacology and Rational Discovery of Multitargeted Drugs
Chapter 3
- IMPROVING ANIMAL MODEL STUDIES TO REDUCE PHASE II ATTRITION
- 3.1. Introduction
- A Notorious Case of the Failure of Animal Studies to Predict Toxicity in
Humans
- The Focus of This Chapter
- 3.2. Case Studies on the Inadequacy of Animal Studies in Neurodegenerative
Diseases
- Animal Studies in Amyotrophic Lateral Sclerosis (ALS)
- Animal Studies Using the "Standard Model" of ALS
- Can Researchers Develop A Better Model of Sporadic ALS?
- Implications of the ALS Animal Model Case for Alzheimer' s Disease (AD)
- Studies in Mouse Models Transgenic For Tau
- 3.3. Lessons from Animal Model Studies in ALS and AD
- 3.4. Another Therapy for AD Based On Targeting Tau
- 3.5. Case Study on Adoption of Improved Mouse Models of Cancer by Industry
- Aveo Pharmaceuticals and Mouse Model Technology Transfer Between Academia
and Industry
Chapter 4
- OVERVIEW OF TRANSLATIONAL MEDICINE AND ITS USE IN DRUG DEVELOPMENT
- 4.1. Defining Responder and Nonresponder Populations
- 4.2. Defining the Optimal Dosing Regimen
- 4.3. Identifying Early, Sensitive Markers of Efficacy
- 4.4. Identifying Patients Who Are Likely to Experience Adverse Effects
- 4.5. Translational Medicine Is Changing the Organization of Clinical
Trials in Some Companies
- Lilly' s Chorus
- Wyeth' s "Learn and Confirm" Organization of Drug Development
- Lessons from the Lilly and Wyeth Cases
Chapter 5
- BIOMARKERS AND THEIR ROLE IN TRANSLATIONAL MEDICINE
- 5.1. Introduction
- 5.2. Types of Biomarkers
- Translational (Bridging) Biomarkers
- Toxicity Biomarkers
- Stratification Biomarkers in Cancer: Case Studies on Epidermal Growth
Factor Receptor (EGFR) Antagonists in Non-Small Cell Lung Cancer (NSCLC) and
Colorectal Cancer
- 5.3. Biomarkers Still an Early-Stage Technology
- 5.4. The Biomarkers Consortium and Improving Biomarker Science
Chapter 6
- NEW STRATEGIES FOR EARLY-STAGE CLINICAL TRIAL DESIGN
- 6.1. Phase 0 Clinical Trials
- Phase 0 Studies at the National Cancer Institute
- European-Based Phase 0 Studies Led by Xceleron
- The Ethics of Phase 0 Studies
- What Can Be Expected From Phase 0 Microdosing Studies?
- 6.2. Adaptive Clinical Trials
- 6.3. Proof-of-Concept Clinical Trials
Chapter 7
- OUTLOOK FOR STRATEGIES TO REDUCE PHASE II ATTRITION
- 7.1. Discussion of Insight Pharma Reports' Phase II Attrition Survey -
January/February 2009
- 7.2. General Conclusions
References
Appendix
EXPERT INTERVIEWS
- A.1. Charles Gombar, PhD, Vice President, R&D Strategy and Business
Improvement, Wyeth Evan Loh, MD, Vice President, Clinical R&D, Wyeth
- A.2. Peter Lassota, PhD, Divisional Vice President, Imaging Biology &
Oncology, Caliper Life Sciences
- A.3. Bruce H. Littman, MD, President, Translational Medicine Associates,
LLC
- A.4. Daniel M. Skovronsky, MD, PhD, Founder and CEO, Avid
Radiopharmaceuticals Company Index with Web Addresses
