Outsourcing in Drug Development: The Contract CRO Market, 3rd Edition

Table of Contents

TABLE OF CONTENTS

CHAPTER ONE: EXECUTIVE SUMMARY

• The Drug Development Process
• Government Regulation of Clinical Researc
• Active Phase I, II & III Clinical Trial
• Phase IV Studies: Post Approval
• Recruiting for Clinical Trial
• The Complexity and Costs Of Clinical Trials Are Increasing
• Clinical Trials Worldwide
• The Contract Drug Development Industry
• R&D Outsourced to Contract Drug Development
• Contract Drug Development Market
• Trends Affecting Growth of Contract Drug Development Industry
  • Globalization of Drug Development
  • Rapid Technological Change Increasing Data
  • Biotechnology Industry Growth
  • Increased Regulatory Scrutiny
  • Need for Fast, Efficient, and Cost-Effective Drug Development
  • Drug Development Process

CHAPTER TWO: INTRODUCTION

• Government Regulation of Clinical Research
• Center for Biological Evaluation and Review
• Center for Drug Evaluation and Research
• Investigational Review Board
• Preclinical Research
• In Vitro and In Vivo Testing Process
• Investigational New Drug Application
• Clinical Trials
• Preclinical Phase
• Phase I
• Phase IIa
• Phase IIb
• Phase III
• Phase IIIa
• Phase IIIb
• Phase IV: Post Approval
• New Drug Applications
• New Molecular Entities and Approval Times
• Accelerated Approval
• Has FDA’s PDUFA ACT Weakened Safety Standards?
• Government Initiatives to Improve Research and the Review Process
• FDA’s Critical Path Report
• Exploratory IND Studies—An Approach to Complying with CGMP
• INDs—Approaches to Complying with CGMP During Phase 1
• Biotechnology Industry Endorses FDA’s Critical Path
• Globalization Trends in Drug Development
• Clinical Trials Worldwide
• China is Ranked First
• India’s Growing Market
• Russia Dominates Eastern Europe

CHAPTER THREE: CLINICAL TRIAL OPERATIONS

• Conducting Clinical Trails
• Government Sponsored Clinical Trials
• Organizations Contracted to Conduct Clinical Trials
• Contract Research Organizations (CROs)
• Managed Site Networks
• Major Elements of Clinical Trials
• Protocol
• Eligibility Criteria
• Endpoints
• Randomization
• Stratification
• Blinding
• Data Collection and Management Tools
• Statistical Interpretation
• Data Collection and Management Tools
• Statistical Interpretation
• Phase IV Studies Post Approval Studies
• Sentinel Initiative
• Recruiting for clinical Trials
• Clinical Trials Recruitment Promotion
• Internet-Enabled Recruitment
• Recruiting Principal Investigators
• Physician as Principal Investigator
• Recruiting Patients
• Use of Homecare Services
• Patient Recruitment Outside the U.S.
• Delays in Patient Recruiting Increases Project Costs
• Factors Influencing Participation in Clinical Trials
• Increasing Complexity of Clinical Trials
• Informed Consent Process
• Demographics and Clinical Trials
• Ethnicity and Gender in Clinical Trials
• Electronic Data Management
• Traditional Paper-based Case Report Forms
• Advantages of EDC
• Current Assessment of EDC Adoption
• Need for an EDC Standard
• FDA Releases Guidance for Using Computerized Systems in
• Clinical investigations
• Electronic Patient Diaries

CHAPTER FOUR: TRENDS

• Drug Development Costs
• Outsourcing Drug Development
• A Brief History of Contract Research Outsourcing
• Focus Shifts in Outsourced Clinical Research Operations from Phase II-III to Phase I to IIIb/IV
• Major Factors Driving Contract Research Outsourcing Strategy
• Outsourcing as a Cost Reduction Strategy
• Number of New Chemical Entities (NCEs) in Pipeline Increasing
• Growing Complexity of Regulatory Requirements
• Outsourcing to Gain Rapid Access to Patient Recruiting
• Contract Research Competitors
• Academic Medical Centers (AMCs)
  • Competing Factors
• Contract Research Organizations (CROs)
  • CRO Contract
• Competing Factors Managed Site Networks
• Competing Factors
• Clinical Trial Laboratories
  • Competing Factors
• Clinical Trials as a Business Opportunity
• Community Physicians
• Electronic Technology Solutions
• Internet Patient/Investigator Recruiting
• Clinical Trials Packaging
• Effective Packaging Promotes Patient Compliance

CHAPTER FIVE: MARKETS

• R&D Spending Increasing
• Leading Pharmaceutical Developers
• Clinical Research Products in Development
• Shift in Spending for Clinical Research
• Spending for Phase I Trials Slows from Highs in 2004
• Safety Issues Drive Phase IIIb/IV Trial Spending
• Contract Drug Research Market
• Contract Research Competitors
• CROs Market Share
• CROs Broaden Services through Acquisitions
• CROs Expanding Laboratory Services
• AMC Market Share
• AMCs Reassess Role in Industry-funded Clinical Research
• Academic Clinical Reseach Organizations Expanding
• Niche Competitors’ Market Share
• Clinical Trial Laboratory Services
• EDC Services Gaining Market Share
• Managed Site Networks
• Trends Affecting Growth in Contract Drug Development Industry
• Globalization of Drug Development
• Rapid Technological Change Increasing Data
• Biotechnology Industry Growth
• Increased Regulatory Scrutiny
• Need for Fast, Efficient, and Cost-Effective Drug Development
• CHAPTER SIX: COMPANY PROFILES
• Charles River Laboratories International, Inc.
• Covance, Inc.
• Encorium Group, Inc.
• Icon, Plc
• Kendle International, Inc.
• MDS Pharma Services
• Omnicare Clinical Research
• Paraxel International Corporation
• Pharmanet Development Inc.
• Pharmaceutical Product Development, Inc.
• Radiant Development
• Clinical Trial Laboratories
• Bioanalytical Research Corporation
• Calvert Laboratories, Inc.
• Kronos Science Laboratories, Inc.
• Medtox Scientific Inc.
• Pacific Biometric, Inc.
• PRL Central Laboratory Services
• Quest Diagnostics, inc.
• TGA Sciences, Inc.
• CNS Clinical Trials
• DaVita Clinical Research
• -USA, Inc.
• Synarc, Inc.
• Advanced Clinical Software
• eTrials Worldwide, Inc.
• Interactive Clinical Technologies, Inc.
• Medidata Solutions Worldwide
• Pharsight Corporation

APPENDIX: COMPANY DIRECTORY

TABLE OF EXHIBITS

CHAPTER ONE: EXECUTIVE SUMMARY

• Exhibit 1-1: The U.S. Drug Discovery, Development, and Approval Process
• Exhibit 1-2: Number of Active Clinical Drug Development Programs (May 11, 2007)
• Exhibit 1-3: Total Average Number of Active Clinical Drug Development Programs, 2001-2007
• Exhibit 1-4: Change in Protocol Eligibility Criteria, Comparison of 1999-2000 and 2003-2006
• Exhibit 1-5: Worldwide Clinical Trial Sites, by Region and Percent, as of 7/12/2008
• Exhibit 1-6: Portion of Global R&D Expenditures Outsourced: 2003-2008 by percent
• Exhibit 1-7: Contract Drug Development Market Share, Percent by Competitor Type (AMC, CRO’s Others), 2007
• Exhibit 1-8: Contract Research Market, Revenue by Competitor, 2002-2012

CHAPTER TWO: INTRODUCTION

• Exhibit 2-1: Investigational New Drug Submissions, 1992-2006
• Exhibit 2-3: Number of Clinical Trials Initiated Annually for U.S. Submissions
• Exhibit 2-4: Median Total Approval Time for Standard NDAs, 1993-2006
• Exhibit 2-5: Median Total Approval Time for Priority NDAs, 1993-2004
• Exhibit 2-6: Median Total Approval Time for Standard NMEs, 1995-2004
• Exhibit 2-7: Median Total Approval time for Priority NMEs, 1995-2004
• Exhibit 2-8: U.S. NMEs 2006 Approvals: Review Times by Drug
• Exhibit 2-10: Median Approval times for Safety vs All Drugs, By Decade
• Exhibit 2-11: Number and Location of Clinical Trial Sites Worldwide, as of 7/12/2008
• Exhibit 2-12: Worldwide Clinical Trial Sites, by Region and Percent, as of 7/12/2008

CHAPTER THREE: CLINICAL TRIAL OPERATIONS

• Exhibit 3-1: Key Clinical Trial Enrollment Statistics for: NMEs Approved in 2000-2006
• Exhibit 3-2: Number of Active Clinical Drug Development Programs (May 11, 2007)
• Exhibit 3-3: Total Average Number of Active Clinical Drug Development Programs, 2001-2007
• Exhibit 3-4: Summary Of Postmarketing Study Commitments (Numbers as of September 30, 2007)
• Exhibit 3-5: Benefits and Risks of Participating in Clinical Trials
• Exhibit 3-6: Change in Protocol Eligibility Criteria, Comparison of 1999-2000 and 2003-2006
• Exhibit 3-7: Aggregate Enrollment Data for All Extramural and Intramural Research Protocols Funded in FY2005 and Reported in FY2006, by Percent and Gender

CHAPTER FOUR: TRENDS

• Exhibit 4-1: New Paradigm for R&D
• Exhibit 4-2: Improvements in the Drug Development Process Reduce Development Costs
• Exhibit 4-3: Portion of Global R&D Expenditures Outsourced: 2003-2008 by percent
• Exhibit 4-4: Percentage of Industry-Sponsored Clinical Trials Awarded to Academic Medical Centers Versus Private Sector Companies: 1991, 1996,2001 and 2006

CHAPTER FIVE: MARKETS

• Table 5-2: Global Drug Development Spending, 2002-2012
• Table 5-2: Global Drug Development Spending, 2002-2012
• Exhibit 5-3: R&D Expenditures of Leading Pharmaceutical Developers, 2006 vs. 2005
• Exhibit 5-4: Number of Companies with Active Product Development Projects, 1997-2006
• Exhibit 5-5: Total Average Number of Active Phase I-III Clinical Trials Worldwide, 2001-2007
• Exhibit 5-6: Top Ten Therapeutic Categories in R&D Worldwide, March 2007
• Exhibit 5-7: A Comparison of Spending Rates in Phase I and Phase II/III Trials, 2004-2008
• Exhibit 5-8: Clinical Trials Phase IIIb/IV Market 2004-2008 (in U.S. billions)
• Exhibit 5-9: Global R&D Spending and Portion Outsourced to Contract Research, 2002-2012 (in US Billions)
• Exhibit 5-10: Contract Drug Development Market, 2002-2012 (Outsourced to CROs, Others)
• Exhibit 5-11: Contract Research Market (CRO, AMC, Other) 127
• Exhibit 5-12: CRO Market Share, 2007
• Exhibit 5-13: Selected Acquisitions of Leading CROs, 2006 to present

TABLE OF EXHIBITS

CHAPTER ONE: EXECUTIVE SUMMARY

• Table 1-1: The U.S. Drug Discovery, Development, and Approval Process
• Exhibit 1-2: Number of Active Clinical Drug Development Programs (May 11, 2007)
• Exhibit 1-3: Total Average Number of Active Clinical Drug Development Programs, 2001-2007
• Exhibit 1-4: Change in Protocol Eligibility Criteria, Comparison of 1999-2000 and 2003-2006
• Exhibit 1-5: Worldwide Clinical Trial Sites, by Region and Percent, as of 7/12/2008
• Exhibit 1-6: Portion of Global R&D Expenditures Outsourced: 2003-2008 by percent
• Exhibit 1-7: Contract Drug Development Market Share, Percent by Competitor Type (AMC, CRO’s Others), 2007
• Exhibit 1-8: Contract Research Market, Revenue by Competitor, 2002-2012

CHAPTER TWO: INTRODUCTION

• Exhibit 2-1: Investigational New Drug Submissions, 1992-2006
• Exhibit 2-3: Number of Clinical Trials Initiated Annually for U.S. Submissions
• Exhibit 2-4: Median Total Approval Time for Standard NDAs, 1993-2006
• Exhibit 2-5: Median Total Approval Time for Priority NDAs, 1993-2004
• Exhibit 2-6: Median Total Approval Time for Standard NMEs, 1995-2004
• Exhibit 2-7: Median Total Approval time for Priority NMEs, 1995-2004
• Exhibit 2-8: U.S. NMEs 2006 Approvals: Review Times by Drug
• Exhibit 2-10: Median Approval times for Safety vs All Drugs, By Decade
• Exhibit 2-11: Number and Location of Clinical Trial Sites Worldwide, as of 7/12/2008
• Exhibit 2-12: Worldwide Clinical Trial Sites, by Region and Percent, as of 7/12/2008

CHAPTER THREE: CLINICAL TRIAL OPERATIONS

• Exhibit 3-1: Key Clinical Trial Enrollment Statistics for: NMEs Approved in 2000-2006
• Exhibit 3-2: Number of Active Clinical Drug Development Programs (May 11, 2007)
• Exhibit 3-3: Total Average Number of Active Clinical Drug Development Programs, 2001-2007
• Exhibit 3-4: Summary Of Postmarketing Study Commitments (Numbers as of September 30, 2007)
• Exhibit 3-5: Benefits and Risks of Participating in Clinical Trials
• Exhibit 3-6: Change in Protocol Eligibility Criteria, Comparison of 1999-2000 and 2003-2006
• Exhibit 3-7: Aggregate Enrollment Data for All Extramural and Intramural Research Protocols Funded in FY2005 and Reported in FY2006, by Percent and Gender

CHAPTER FOUR: TRENDS

• Exhibit 4-1: New Paradigm for R&D
• Exhibit 4-2: Improvements in the Drug Development Process Reduce Development Costs
• Exhibit 4-3: Portion of Global R&D Expenditures Outsourced: 2003-2008 by percent
• Exhibit 4-4: Percentage of Industry-Sponsored Clinical Trials Awarded to Academic Medical Centers Versus Private Sector Companies: 1991, 1996,2001 and 2006

CHAPTER FIVE: MARKETS

• Table 5-2: Global Drug Development Spending, 2002-2012
• Table 5-2: Global Drug Development Spending, 2002-2012
• Exhibit 5-3: R&D Expenditures of Leading Pharmaceutical Developers, 2006 vs. 2005
• Exhibit 5-4: Number of Companies with Active Product Development Projects, 1997-2006
• Exhibit 5-5: Total Average Number of Active Phase I-III Clinical Trials Worldwide, 2001-2007
• Exhibit 5-6: Top Ten Therapeutic Categories in R&D Worldwide, March 2007
• Exhibit 5-7: A Comparison of Spending Rates in Phase I and Phase II/III Trials, 2004-2008
• Exhibit 5-8: Clinical Trials Phase IIIb/IV Market 2004-2008 (in U.S. billions)
• Exhibit 5-9: Global R&D Spending and Portion Outsourced to Contract Research, 2002-2012 (in US Billions)
• Exhibit 5-10: Contract Drug Development Market, 2002-2012 (Outsourced to CROs, Others)
• Exhibit 5-11: Contract Research Market (CRO, AMC, Other)
• Exhibit 5-12: CRO Market Share, 2007
• Exhibit 5-13: Selected Acquisitions of Leading CROs, 2006 to present