Outsourcing in Drug Development: The Contract Research (CRO) Market, 2nd Edition

Table of Contents

chapter one: Executive Summary

• The Drug Development Process

• Government Regulation of Clinical research

• Clinical Trials Operations

• Government Sponsored Clinical Trials

• Private Sector Sponsored Clinical Trials

• Designing Clinical Trials

• Major Elements of Clinical Trials

• Active Phase I, II & III Clinical Trials

• Phase IV Studies: Post Approval

• Recruiting for Clinical Trials

• Electronic Data Capture and Electronic Data Management

• Competing in the Contract Drug Development Industry

• Academic Medical Centers and Teaching Hospitals

• Contract Research Organizations

• Preclinical and Clinical Laboratories

• Site Management Organizations

• Niche Service Providers

• Electronic Technology Solutions

• Internet Patient Recruiting

• Clinical Trials Packaging

• Contract Drug Development Market

• Contract Drug Development Competitors and Market

chapter two: Introduction to Drug Development

• Drug Development Process

• 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 Application

• New Molecular Entities and Approval Time

• Significant New Products Approved in 2004

• Fast Track, Priority Review, and Accelerated Approval

• Fast Track Approval

• Average Approval Time for Fast Track Designated Drugs

• Priority Review

• Accelerated Approval

• Does Speeding the Approval Process Lead to an Increase in Drugs Withdrawn from Market?

• FDA Initiative to Improve Research and 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

chapter three: Clinical Trials Operations

• Conducting Clinical Trails

• Organizations Conducting Clinical trials

• Government Sponsored Clinical Trials

• Private Sector-Sponsored Clinical Trials

• Contract Research Organizations (CROs)

• Site Management Organizations (SMOs)

• Designing Clinical Trials

• Major Elements of Clinical Trials

• Protocol

• Eligibility Criteria

• Endpoints

• Randomization

• Stratification

• Blinding

• Data Collection and Management Tools

• Statistical Interpretation

• Active Phase I, II & III Clinical Trials

• Phase IV Studies: Post Approval

• Post Approval Commitments

• Recruiting for Clinical Trials

• Recruiting Costs

• Mass Media Recruitment Promotion

• Recruiting Principal Investigators

• Physician as Principal Investigator

• Recruiting Patients

• Factors Influencing Participation in Clinical Trials

• Clinical Trial Metrics

• Participant Retention

• Number of Sites per Phase; Number of Patients per Phase

• eRecruitment: Internet-Enabled Recruitment

• Informed Consent Process

• Demographics and Clinical Trials

• Ethnicity and Gender in Clinical Trials

• Electronic Data Capture and Electronic Data Management

• Traditional Paper-Based Case Report Forms

• Advantages of EDC

• Current Assessment of EDC Adoption

• Need for an EDC Standard

• FDA Encourages EDC Systems

• Electronic Patient Diaries

chapter four: Competing in the Contract Drug Development Industry

• Drug Development Costs

• Outsourcing Drug Development

• A Brief History of Contract Research Outsourcing

• Focus Shifts in Outsourced Clinical Research Operations

• Factors Driving Contract Research Strategy

• Cost Reduction Strategy

• Increasing Number of New Chemical Entities (NCEs) in Pipeline

• Time to Market Pressures

• Growing Complexity of Regulatory Requirements

• Rapid Access to Patient Recruiting

• Contract Research Competitors

• Academic Medical Centers and Teaching Hospitals

• Contract Research Organizations

• CRO Contracts

• Competing Factors

• Preclinical and Clinical Laboratory Services

• Competing Factors

• Site Management Organizations

• 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: Contract Drug Development Market

• Trends in Drug Development Spending

• Pharmaceutical Companies: R&D Spending

• Biopharmaceutical Companies: R&D Spending

• Clinical Research Projects in Development

• Contract Drug Development Market

• Phase I Spending Outpaces Phase II/III Trials

• Phase IIIb/IV Trial Spending Increasing

• Contract Drug Development Competitors and Market

• CROs Dominate Outsourced Drug Development Market

• Leading CROs’ Market Share

• CROs Broaden Services through Acquisitions

• AMCs Market Share Stabilizing

• Growth of Academic Clinical Reseach Organizations

• SMOs See Modest Gains

• SMOs in Transition

• Transitioning from SMO to CRO

• Niche Competitors Gain Market Share

• Central Laboratories

• EDC Competitors Positioned for Big Gains

• Regulatory Agencies Driving Adoption of EDC

• EDC Market Estimates

• 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

• Contract Research Organizations

• Charles River Laboratories International, Inc.

• History and Lines of Business

• Drug Development Services

• Preclinical Services

• Clinical Services

• Financial Information

• Covalent Group, Inc.

• History and Lines of Business

• Drug Development Services

• Clinical Trial Services

• Data Management Services

• Biostatistics

• Automated Database System

• Financial Information

• Covance, Inc.

• History and Lines of Business

• Drug Development Services

• Preclinical Services

• Phase I Clinical Services

• Central Laboratory Services

• Clinical Development Services

• Commercialization Services

• Financial Information

• ICON Clinical Research

• History and Lines of Business

• Drug Development Services

• Financial Information

• Kendle International, Inc.

• History and Lines of Business

• Drug Development Services

• Clinical Development (Phases I to III)

• Regulatory Affairs

• Biometrics

• Late Phase

• Financial Information

• MDS Pharma Services

• History and Lines of Business

• Drug Development Services

• Early Stage Development

• Metabolism Resource

• Early Clinical Research

• Late Stage Development

• Global Clinical Development

• Financial Information

• Omnicare Clinical Research

• History and Lines of Business

• Drug Development Services

• Financial Information

• Parexel International Corporation

• History and Lines of Business

• Drug Development Services

• Clinical Development Services

• Consulting Services

• Medical Marketing Services

• Advanced Technology

• Publications

• Financial Information

• Pharmaceutical Product Development, Inc.

• History and Lines of Business

• Drug Development Services

• Phase I Clinical Testing

• Phase II through Clinical Trial Management

• Clinical Data Management and Biostatistical Analysis

• Medical Writing and Regulatory Services

• Safety/Pharmacovigilance

• Post-Approval Services and Market Development Support

• Informatics

• Financial Information

• Quintiles Transnational Corporation

• History and Lines of Business

• Drug Development Services

• Early Development and Services

• Clinical Development Services

• Financial Information

• SFBC International, Inc.

• History and Lines of Business

• Drug Development Services

• Early Phase Clinical Services

• Late Phases Clinical Services

• General Drug Development Services

• Financial Information

• Preclinical and Clinical Laboratories

• Bioanalytical Research Corporation

• History and Lines of Business

• Contract Laboratory Services

• Quality Assurance:

• Worldwide Logistics

• Custom Designed Supplies and Documentation

• Project Management

• Customized Reporting

• Remote Data Access

• Electronic Data Transfer

• Calvert Laboratories, Inc.

• History and Lines of Business

• Contract Laboratory Services

• General Pharmacology

• CRL Medinet

• History and Lines of Business

• Contract Laboratory Services

• Data Management

• Study Management

• Huntingdon Life Sciences

• History and Lines of Business

• Contract Laboratory Services

• Kronos Science Laboratories, Inc.

• Contract Laboratory Services

• Medtox Scientific Inc.

• History and Lines of Business

• Contract Laboratory Services

• Financial Information

• Pacific Biometric, Inc.

• History and Lines of Business

• Contract Laboratory Services

• Perry Scientific, Inc.

• History and Lines of Business

• Laboratory Contract Services

• Pharmacokinetic, ADME and Efficacy Studies

• Preclinical MRI Imaging

• Cell and Tissue Culture

• Dermatological Studies

• Drug and Device Efficacy Studies

• Surgical Studies

• Toxicology Screening

• Studies with Human Tissue

• PRL Central Laboratory Services

• History and Lines of Business

• Contract Laboratory Services

• Laboratory Data Management Solutions

• Effective Execution for Protocol Compliance

• Clinical Laboratory Science-A PRL Core Competency

• Synarc, Inc.

• History and Lines of Business

• Contract Laboratory Services

• TGA Sciences, Inc.

• History and Lines of Business

• Contract Laboratory Services

• Assay Development

• Assay Validation

• Sample Handling and Analysis

• In Vivo Animal Studies

• FACS Analysis

• Site Management Organizations

• Accelovance

• History and Lines of Business

• Clinical Trials Services

• CNS Clinical Trials

• History and Lines of Business

• Clinical Trials Services

• Phase I

• Phase II-IV

• Other Services

• DaVita Clinical Research

• History and Lines of Business

• Clinical Trials Services

• Clinical Trials I

• Clinical Trials II-IV

• General Clinical Trial Services

• Features of Facilities include:

• JFJ Research Services, Inc.

• History and Lines of Business

• Clinical Trial Services

• Project Management

• Subject Recruitment

• Radiant Research

• History and Lines of Business

• Clinical Trials Services

• Patient Recruitment Services

• Call Center Services

• Training Participant Screeners

• Telephone Screening Process

• Periodic Reporting

• Media Development and Placement

• Project Management

• Research Solutions LLC

• History and Lines of Business

• Clinical Trial Services

• Centralization of Clinical Trial Start-up

• Clinical Operations

• Information Technology

• Investigator Services

• Qualified Experienced Investigators

• Patient Recruitment and Call Center

• SMO-USA, Inc.

• History and Lines of Business

• Clinical Trial Services

• Highly Experienced Principle Investigators

• Trial Manager

• Access to a Large Patient Study Population

• Patient Recruiting

• Niche Competitors

• Acurian, Inc.

• History and Lines of Business

• Clinical Trial Services

• AcuPatient: Accelerate Patient Recruitment

• AcuSite: Select the Right Investigator

• AcuChart: Target Investigator’s Patient Population

• Advanced Clinical Software

• History and Lines of Business

• Clinical Trials Services

• Study Manager Web Edition

• Study Recruiter

• StudyWeb Information and Collaboration System

• Clinical Trial Services

• History and Lines of Business

• Clinical Trials Services

• Manufacturing, Primary and Secondary Packaging Services

• Specialized Manufacturing/Packaging Services

• Labeling Services

• Storage, Distribution and Returns Services

• Analytical Services

• Specialist Clinical Management

• eResearch Technology, Inc.

• History and Lines of Business

• Clinical Trial Services

• eResearch Network Technology: eResNet

• eData Entry Technology: eDE

• eResCom

• eStudy Conduct

• eData Management

• EXPeRT”eECG

• eSafety Net

• Financial Information

• eTrials Worldwide, Inc.

• History and Lines of Business

• Clinical Trials Services

• Electronic Data Capture

• Electronic Patient Reported Outcomes: ePRO

• Randomized Enrollment Module

• Site Management

• Supplies Management

• Analytics

• Reporting

• Electronic Diaries

• QuickStudy Voice

• ASCompare: Electronic Data Review

• Regulated Compliant Systems

• Interactive Clinical Technologies, Inc.

• History and Lines of Business

• Clinical Trials Services

• Interactive Voice Response System (iVRS)

• iTrial EDC

• iDiary (ePRO)

• Statistical Services

• Clinical Supplies Forecasting

• Clinical Hotline

• EZ-link Total Clinical Supply Management

• Data Integration

• Adaptive Trial Design

• Quality Services

• Fast Track Systems, Inc.

• History and Lines of Business

• Clinical Trials Services

• TrialSpace Designer (TSD)

• CROCAS PBT

• TrialSpace Grants Manager

• Consulting Services

• Fisher Clinical Services

• History and Lines of Business

• Clinical Trial Services

• Manufacturing Services

• Label Printing Services

• Storage & Global Distribution Services

• IVR Services (FACTS)

• Return Accountability & Destruction

• Outcome Sciences, Inc.

• History and Lines of Business

• Clinical Trial Services

• Perceptive Informatics, Inc.

• History and Lines of Business

• Clinical Trial Services

• CTMS (Clinical Trials Management Systems)

• IVRS (Interactive Voice Response Systems)

• Portals

• Imaging

• Integration

• Financial Information

• Pharsight Corporation

• History and Lines of Business

• Clinical Trials Services

• WinNonlin and WinNonMix

• PharsightKnowledgebase Server (PKS)

• Trial Simulator

• Drug Model Explorer (DMX)

• Financial Information

• Phase Forward, Inc.

• History and Lines of Business

• Clinical Trial Services

• InForm

• Clintrial

• Clintrace

• WebVDME

• CTSD

• WebSDM

• Product Integration

• Financial Information

List of Exhibits

chapter one: Executive Summary

• Figure 1-1: The U.S. Drug Discovery, Development, and Approval Process

• Figure 1-2: U.S. Clinical Trial Enrollment Delays Worsen

• Figure 1-3: Projecting Phase I-IIIB/IV Projects Using EDC in 2004

• Figure 1-4: A Ten-Year Historical Perspective: Growth of Outsourcing in Drug Development, 1993-2003

• Table 1-1: Global Drug Development Expenditures and Outsourced Drug Development Spending 2000-2010

• Figure 1-5: Contract Drug Development Market Share by Competitor Type (Academic Medical Centers, Site Maintenance Organizations, Contract Research Organizations) 2005

• Table 1-2: Market Summary: Contract Drug Development Market 2001, 2005, 2010

chapter two: Introduction to Drug Development

• Table 2-1: Number of IND Submissions for Drugs 1992-2004

• Figure 1-1: The U.S. Drug Discovery, Development, and Approval Process

• Table 2-2: Number of Clinical Trials Initiated Annually for U.S. Submissions by Type

• Table 2-3: Median Total Approval Time for Standard NDAs 1993-2004

• Table 2-4: Median Total Approval Time for Priority NDAs, 1993-2004

• Table 2-5: Median Total Approval Time for Standard NMEs 1995-2004

• Table 2-6: Median Total Approval time for Priority NMEs 1995-2004

• Figure 2-2: Median Approval times for Safety vs All Drugs, By Decade

• Figure 2-3: Approval Times for Priority, Standard and Fast Track Approvals, 1998-present

chapter three: Clinical Trials Operations

• Table 3-1: Key Clinical Trial Enrollment Statistics for NMEs Approved in 1999-2004 (Mean Patients per NDA; Median Patients per NDA; Range)

• Table 3-2: Number of Active Clinical Drug Development Programs (March 2005)

• Table 3-3: Total Average Number of Active Clinical Drug Development Programs by Year, 2001-2005

• Figure 3-1: NME Approvals in the U.S. with Post Approval Commitments

• Table 3-4: Summary of Post-Marketing Study Commitments as of 30-Sep-05

• Figure 3-2: U.S. Clinical Trial Enrollment Delays Worsen

• Table 3-5: Total Spending on Mass Media Recruitment Promotion 1998-2003

• Table 3-6: Benefits and Risks of Participating in Clinical Trials

• Table 3-7: Clinical Trials Retention Rates, Phases I-IV

• Figure 3-3: Average Number of Sites by Phase

• Figure 3-4: Average Number of Patients by Phase

• Table 3-8: Aggregate Enrollment Data for All Extramural Research Protocols Reported in 2003 (Number and Percentage of Total) by Race/Ethnicity and Sex

• Table 3-9: Aggregate Enrollment Data for Intramural Research Protocols Conducted On-Site and Off-Site, 2003 (Number and Percentage of Total) by Race/Ethnicity and Sex

chapter four: Competing in the Contract Drug Development Industry

• Table 4-1: New and Old Paradigms for Pharmaceutical R&D

• Table 4-2: Improvements in the Drug Development Process Reduce Development Costs (Quantification of Time, Success, and Expense Improvements)

• Figure 4-2: Trending in R&D Spending Growth Rate, 1993-2003

• Figure 4-3: Trending in Outsource Spending Growth Rate, 1993-2003

• Figure 4-4: A Ten-Year Historical Perspective: Growth of Outsourcing in Drug Development, 1993-2003 (Total R&D Spending vs Total Outsource Spending)

• Table 4-3: Academic Medical Centers vs. Independent Sites: Percentage of Industry-Sponsored Clinical Trials 1991-2006

chapter five: Contract Drug Development Market

• Table 5-1: Global Drug Development Spending 2000-2010

• Table 5-2: R&D Spending in 2004 of Top Pharmaceutical Companies, Ranked by 2004 Sales

• Figure 5-1: Mean Total Development Times* for Pharmaceuticals and Biologic Products Approved in the United States by Time Period 1985-1989, 1990-1994, 1995-1999, 2000-2004

• Table 5-3: R&D Spending in 2004 of Top Biopharmaceutical Companies, Ranked by 2004 Sales

• Table 5-4: Number of Companies with Active Product Development Projects, 1997-2004

• Table 5-5: Worldwide Active R&D Projects in Development by Stage 1998-2005

• Table 5-6: Number of Compounds in R&D in the United States by Top Ten Therapeutic Categories, 2004

• Table 5-7: Number of Compounds in R&D Worldwide by Top Twelve Therapeutic Categories March 2005 vs March 2004.

• Table 5-8: Global Drug Development Expenditures and Outsourced Drug Development Spending 2000-2010

• Table 5-9: World Preclinical and Phase I Clinical Trials Market 2003-2008

• Table 5-10: World Clinical Trials Phase IIIb/IV Market 2003-2008

• Figure 5-2: Contract Drug Development Market Share by Competitor Type (Academic Medical Centers, Site Maintenance Organizations, Contract Research Organizations) 2005

• Table 5-11: Contract Drug Development Market 2000-2010

• Table 5-12: Contract Drug Development Market by Competitor Type (CROs, AMCs, SMOs, and Others) 2000-2010

• Table 5-13: Revenues and Market Share of Publicly-Traded CROs 2004

• Table 5-14: Selected Acquisitions by CROs 2004 to Present

• Table 5-15: Annual Growth in Number of Trials Using an SMO, 2000-2004

• Figure 5-3: Driving Forces Accelerating and Limiting IT Improvements over the Next 3 to 5 Years

• Figure 5-4: Percent of Phase I-IV Trials using EDC, Sponsors vs. CROs 2000-2004

• Figure 5-5: Electronic Data Capture Market 2000-2004