1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 Worldwide Pharmaceutical Market Estimated Size, 2001-2008 Major World Markets Population Size and Sales Growth Global Pharma Sales by Region 2005-2006 Pharmaceutical Sales by Region Share of Worldwide Market Global Pharma Sales Growth by Region Top Ten Pharma Markets 2002, 2006, 2010 Fastest Growing Pharmaceutical Markets Top 10, 2004-2005 Ethical Pharmaceutical Sales Growth Rate, 1997-2006 Ethical Pharmaceutical Sales Selected Emerging Markets Major European Pharmaceutical Sales Central and Eastern Europe Pharmaceutical Sales, 2001-2006 Ethical Pharmaceutical Sales Total PhRMA-Member-Company Sales, 1994-2006 Ethical Pharmaceutical Sales Total PhRMA-Member-Company Sales, 2000-2006 Central & Eastern Europe Sales Pharmaceutical Market Share of Select Countries Pharmaceutical Market in Canada 2003-2007 Pharmaceutical Use in Ascending Markets 2001-2015 Pharmaceutical Sales in Latin America Breakdown of Market Share, by Country Pharmaceutical and Medicine Manufacturing in Africa 2005 Worldwide Ethical Pharmaceutical Sales Top Therapeutic Classes, 2006
x 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 1.33 1.34 1.35 1.36 1.37 1.38 1.39 1.40 Top Ten Worldwide Drug Sales 2006 Top 10 Orphan Drug Sales 2007 Top Ten Pharmaceutical Companies 2007 Revenues Top Ten Biotechnology Companies 2007 Revenue Worldwide Medical Device Market Projected Sales, through 2009 U.S. Medical Device Market Projected Sales 2004-2009 Worldwide Medical Device Sales 2004 Estimated Market Share, by Region Medical Device Market Largest Treatment Areas by Total Sales, 2003 Select Medical Device Manufacturers Total Revenues, 2007 Medical Devices Worldwide and U.S. Revenues Generic Pharmaceutical Market Total Worldwide Sales, 1998-2003 Generic Pharmaceutical Market Total U.S. Sales, 2002-2006 Top 10 Generic Companies 2006 Revenue Top Ten Generic Molecules by Sales 2007 Generics Take Larger Share Percent of Total Prescriptions Sold Generic Share of Prescriptions 1998-2005 Generic Substitution Rates Select Countries U.S. Prescriptions 2002-2006 Market Share Lost 12 Months after Patent Expiration Sales Vulnerable to Generic Competition Selected Top Companies Through 2012 Top Drugs Facing Generic Competition U.S., by Year 2.01 2.02 2.03 2.04 2.05 2.06 2.07 A New Wave of Pipeline Growth Projects Worldwide (Discovery Clinical) NME Approval and Domestic R&D Expenditure 1996-2006 Projected R&D Spending Pharmaceutical and Biotech Companies, 2005-2010 R&D Spending Growth Rates PhRMA Member Companies, 1980-2005 World R&D Market Share PhRMA Member Companies Domestic R&D Spending PhRMA Member Companies, 1996-2006 R&D Spending Abroad PhRMA Member Companies, 1996-2006
xi 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 2.29 2.30 2.31 2.32 R&D Spending Top Ten Pharmaceutical Companies, 2007 R&D Spending Top Ten Biotechnology Companies, 2007 R&D Spending as a Percent Of Sales PhRMA Member Companies R&D Spending as a Percent of Sales Distribution by Industry Type, 2005 Projected R&D as a Percent Of Sales Worldwide Spending, through 2010 The Cost of Developing A Single Drug Total Capitalized Costs, in Constant 2005 Dollars Costs per Approved Biopharmaceutical Total Spending on Clinical Collaborations PhRMA Member Companies Clinical Development Total PhRMA-Member Spending in the U.S., by Phase Spending on Phase IV Trials PhRMA Member Companies Spending on Development Projected Spending, by Phase Spending on Development Projected Spending 2005-2007 PhRMA Member R&D Spending Expenditure by Function, 2005 Distribution of R&D % Total Funding Across Top Therapeutic Areas, 1999-2007 Distribution of R&D Funding by Therapeutic Area, 2004 Pharmaceutical R&D Funding by Therapeutic Area, 1999-2007 Sources of Trial Funding Industry and Government Sponsored R&D Expenditure 2002-2006 Total NIH Grants Grants to All Research Interests, 1999-2006 NIH Grants to Foreign Countries Grants to All Research Interests, 2000-2006 International NIH Grant Recipients Top Recipients by Country, 2006 NIH Grants by Disease: Distribution of Funding by Therapeutic Area, 2005E Federally-Funded Clinical Research Distribution of 2007 Funding, by Source NIH Budget, FY 2007 Distribution of Total NIH Budget, by Destination New NIH Grants Type I Research Project Grants, 1998-2007
xii 2.33 2.34 NIH Funding by Region Top 10 States and International by Total Grant Amount, 2007 NIH Funding per Capita Top Ten States, 2007 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 Worldwide Clinical Trials Estimated Phase I-III Trials, 2000-2006 Clinical Trial Initiations based in FDA-1572, 1990-2006 The Clinical Development Cycle Distribution of Clinical Development Active Projects by Phase, as of December, 2007 Clinical Trials Per NDA Mean Number of Trials in Drugs Reaching Approval, by Phase A New Wave of Pipeline Growth Projects Worldwide (Discovery Clinical) Clinical Innovation NMEs/BLAs Submitted to the FDA, by Year Odds of Successful Development Chance of IND-accepted Drug Entering a Development Phase Drugs in Development by Therapeutic Area Total Active INDs at Year End 2006 for Top Categories Commercial Pipeline Focus Number of Active INDs at Year s-end 2005 Commercial Pipeline Focus Distribution of Commercial & Non- Commercial INDs 2006 Therapeutic Area Growth Growth in Number of Active INDs 2005 to 2006 NCE Approval Success Rates By Therapeutic Class R&D Pipelines of Top Companies Number of Total Drugs in Development, 15 Largest Pipelines R&D Pipelines of Top Companies Number of Own-Drugs in Development, 15 Largest Pipelines Licensing among top 10 Pharmas Top Six Pharmaceutical Pipelines Total Drugs in Development, Including Collaborations The Pharmaceutical Development Cycle Total Cycle Time: 20 Years Clinical and Approval Times Total time, 2000-2006 Average Clinical Development Time Median Total Time from IND to Approval
xiii 3.21 3.22 3.23 3.24 3.25 3.26 3.27 3.28 3.29 3.30 3.31 3.32 3.33 3.34 3.35 3.36 3.37 3.38 3.39 3.40 3.41 3.42 3.43 3.44 3.45 Comparing Cycle Times by NCE Type Average Time, in Years Comparing Development Times Mean Time from First Synthesis to Approval for NMEs Approved 2001 The Potential Cost of Delays Worldwide Sales for the Top 5 Blockbuster Drugs, 2006 Mean Exclusivity for first-in-class Approvals Drugs in Pediatric Trials Distribution of Projects, by Phase Drugs in Pediatric Trials Distribution of Projects, by Phase 2007 Drugs in Pediatric Development Top Five Therapeutic Areas Sponsors Conducting Pediatric Trials Top 5 Sponsors, by Number of Pediatric Development Projects Grants of Pediatric Exclusivity Grants of Pediatric Exclusivity by Type Pediatric Exclusivity Written Requests Written Requests by FDA Review Division Proposed Pediatric Study Requests by FDA Review Division Studies Requested, Pediatric Patients Needed Post-Marketing Commitments Pediatric Components Relating Cost and Speed Average Cost of One Day of Clinical Development, 2005 Sponsor Development Time Goals Average Clinical Development Time Mean Total Time by Therapeutic Area and Phase Average Clinical Development Time Mean Total Time by Therapeutic Area and Phase, Successful Trials Average Clinical Development Time Mean Total Time by Therapeutic Area and Phase, Unsuccessful Trials Average Clinical Development Time Mean Total Time by Company Size and Phase, All TAs Odds of Successful Development Chance of Drug Completing Each Development Phase Time to Completing Phase for Successful and Failed Trials Weeding Out Failures Earlier Increases in Phase I Spending Improve Phase III Success Scope of Clinical Projects Mean Number of Subjects and Sites per Trial
xiv 3.46 3.47 3.48 3.49 3.50 3.51 3.52 3.53 3.54 3.55 3.56 3.57 3.58 3.59 3.60 Causes of Study Initiation Delays Europe Causes of Study Initiation Delays United States Enrollment Delays Distribution of Delays in Site Enrollment Timeliness Enrollment Delays Distribution of Delays in Site Enrollment Timeliness Differences in Phase I trials Index of Number of Subjects in Phase I Trials for Selected TAs Differences in Phase I trials Index of Number of Sites in Phase I Trials for Selected TAs Differences in Phase II trials Index of Number of Subjects in Phase II Trials for Selected TAs Differences in Phase II trials Index of Number of Sites in Phase II Trials for Selected TAs Differences in Phase III trials Index of Number of Subjects in Phase III Trials for Selected TAs Differences in Phase III trials Index of Number of Sites in Phase III Trials for Selected TAs Cost of U.S. Clinical Trials Mean Cost per Patient, by Phase, 2001-2006 Cost of U.S. Clinical Trials Median Cost per Patient, by Therapeutic Area 2001-2006 Rising Project Complexity Mean Number of Procedures per Patient, 1996-2005 Rising Project Complexity Mean Number of Procedures per Patient by Phase, 2001-2006 Sample Patient Reduction from Adaptive Trial Approach 5.01 5.02 5.03 5.04 5.05 5.06 Factor Most Often Causing Study Delays United States Factor Most Often Causing Study Delays Europe Factor Most Often Causing Study Delays Asia Pacific Enrollment Delays Distribution of Delays in Site Enrollment Timeliness Enrollment Delays Distribution of Delays in US Site Enrollment Timeliness Enrollment Delays Distribution of Delays in European Site Enrollment Timeliness
xv 5.07 5.08 5.09 5.10 5.11 5.12 5.13 5.14 5.15 5.16 5.17 5.18 5.19 5.20 5.21 5.22 5.23 5.24 5.25 5.26 5.27 5.28 5.29 5.30 5.31 5.32 5.33 5.34 5.35 Factors That Could Best Prevent Future Delays United States Factors That Could Best Prevent Future Delays Europe Factors That Could Best Prevent Future Delays Asia Pacific EDC as a Factor That Could Best Prevent Future Delays Factors That Can Best Prevent Future Study Delays Factors That Could Best Prevent Future Delays How Has Sponsor Performance Changed In Past Three Years With Regards To United States How Has Sponsor Performance Changed In Past Three Years With Regards To Europe How Has Sponsor Performance Changed In Past Three Years With Regards To Asia Pacific Average Rating For The Typical Sponsor United States Average Rating For The Typical Sponsor Europe Top Rated Sponsors United States Top Rated Sponsors Europe Highest Frequency as a Top 3 Rated Sponsor Across 27 Relationship Attributes United States Highest Frequency as a Top 3 Rated Sponsor Across 28 Relationship Attributes Europe Quality of General Project Management United States Quality of General Project Management Europe Quality of the Study Initiation Process United States Quality of the Study Initiation Process Europe Quality of the Grant Payment Process United States Quality of the Grant Payment Process Europe Quality of Staff Professionalism United States Quality of Staff Professionalism Europe Quality of Workstyle United States Quality of Workstyle Europe Quality of Ongoing Study Support United States Quality of Ongoing Study Support Europe General Project Management Evaluated United States Project Attributes Evaluated I (U.S.)
xvi 5.36 5.37 5.38 5.39 5.40 5.41 5.42 5.43 5.44 5.45 5.46 Project Attributes Evaluated II (U.S.) Personnel & Work Style Evaluated (U.S.) Relationship Attributes Evaluated Europe Relationship Attributes Evaluated Europe Relationship Attributes Evaluated Europe Relationship Attributes Evaluated Europe Comparing Performance Quality With Category Importance United States Comparing Performance Quality With Category Importance Europe Essential Attributes to Study Success United States 2007 Essential Attributes to Study Success Europe 2006 Essential Attributes to Study Success Latin America 2005 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 Worldwide CRO Market Historical and Projected Distribution, by Region Worldwide CRO Market CRO Market Size and Growth Rate, 2005-2010 Number of Clinical CROs CROs in Europe and North America Shifting Share of Clinical Projects Share of Industry-Sponsored Projects Pharmaceutical R&D Spending Outsourced R&D Growth Outpacing Growth in Total R&D CRO Involvement Use of CRO Services Sponsors Reasons for Outsourcing Trial Efforts Top Niche CRO Services Utilized Top Niche CRO Services Utilized 2003 & 2005 CRO Usage in Phase I - III Projects Percent of Clinical Projects where CRO Played Significant Role Top Public CRO Companies Total Revenues CRO Revenue Growth Rates Year-over year revenue growth GAAP EPS Changes Closing Share Price Range 2007 Calendar Year Closing Share Price Range 2006 Calendar Year CRO Acquisitions Total Acquisitions of Clinical CROs 1998-2007
xvii 6.17 6.18 6.19 6.20 6.21 6.22 6.23 6.24 6.25 6.26 6.27 6.28 6.29 6.30 6.31 6.32 6.33 6.34 6.35 6.36 6.37 6.38 6.39 6.40 6.41 6.42 6.43 6.44 Select CRO Acquisitions of Phase I Operations 2006 Select CRO Acquisitions 2005 Select CRO Acquisitions 2006 Part 1 Select CRO Acquisitions 2006 Part 2 Estimated Revenue Matrix Select Public CROs CRO Performance Sites Rating CRO Services Very Important and Excellent Attributes More Important for CROs than Sponsors 2006 Attributes More Important for CROs than Sponsors 2007 CRO Performance 2007 US Site Ratings of CRO Relationship Quality CRO Performance 2006 European Site Ratings of CRO Relationship Quality Comparing CRO Performance Quality With Category Importance United States Comparing CRO Performance Quality With Category Importance Europe Top CROs in the U.S. Sites Rating Overall Quality Good & Excellent Highest Frequency as a Top 3 Rated CRO Across 29 Relationship Attributes CRO Project Management United States CRO Professionalism & Work Style United States CRO Project Initiation & Grant Payment United States CRO Ongoing Study Conduct United States CRO Project Management Europe CRO Professionalism & Work Style Europe CRO Project Initiation & Grant Payment Europe CRO Ongoing Study Conduct Europe CRO Performance Ratings of CROs by American Sites CRO Performance Ratings of CROs by European Sites Top Rated CROs in the U.S. Select Project Attributes SMO Market Size Worldwide Total Sales of SMO Services, 1996-2004 SMOs in Clinical Trials Reported Annual Growth in Clinical Trials Conducted by SMOs Number of SMOs Worldwide Totals by Region, 2006
xviii 6.45 6.46 6.47 6.48 6.49 6.50 6.51 6.52 SMO Company Size Distribution of SMOs, by Number of Investigators SMO Company Size Distribution of SMOs, by Number of Sites SMO Announcements Major Developments in the SMO Industry, 2003 SMO Announcements Major Developments in the SMO Industry, 2004 SMO Announcements Major Developments in the SMO Industry, 2005 Select Trial Management Organizations Select Study SMOs Select Study Brokers/TMOs 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 7.15 7.16 7.17 Trial Outsourcing Distribution Outsourced Trials by Provider Type, 2006 Outsourcing Expenditure Percentage of R&D Expenditure Outsourced Industry Grants per Trial 2002-2007 Selecting Countries for Multinational Trials Key Criteria Used by Sponsors Investigative Site Operating Concerns Most Frequent Responses What is the biggest challenge you face today? Investigative Site Perceptions of Changes in Profit per Grant Sponsor and CRO Payment Tardiness Site Perceptions of Changes in Payment Timeliness Reported Operating Margins Average across Investigative Sites Average Site Expenditures Typical Investigative Site Revenue Allocation 2007 Grants vs Volume Clinical Trial Laboratory Services Total Sales, 2004-2010 EDC Solutions Estimated Market Size, 2001-2007 Which Statement Best Describes The Type Of Electronic Medical Record That You Use? Biotech Infrastructure Expenditure Spend on Technology 2005 Highest Degree Attained by Outsourcing Department Personnel
xix 7.18 7.19 7.20 7.21 7.22 7.23 7.24 7.25 7.26 7.27 7.28 7.29 7.30 7.31 7.32 7.33 7.34 7.35 7.36 7.37 7.38 7.39 7.40 7.41 7.42 7.43 7.44 7.45 7.46 7.47 7.48 7.49 Outsourcing Department Reporting Structure Outsourcing Department Staffing Profile Changes in Outsourcing Department Headcount During Past 12-18 Months Location of Outsourcing Department Personnel Summary of Outsourcing Department Functions Top Regions Handled by Outsourcing Departments Top Services Provided by Outsourcing Departments Distribution of Services Provided by Outsourcing Departments Staff Workload How Department is Initially Engaged Top Three Department Responsibilities Primary Department Responsibilities Primary Department Responsibilities 2003 & 2005 Criteria Used to Measure Outsourcing Department Effectiveness Department Impact on Clinical Projects Last Year Impact on Clinical Projects 2003 & 2005 Frequency of Preparing Justification Ideal Metrics Departments are Looking to Achieve Ideal Metrics Comparisons 2003 & 2005 Types of Contracts Responsible For Top Factors Rated Important When Selecting a Vendor Importance of Vendor Selection Criteria Full-Service and Niche Vendor Selection Criteria Outsourcing Strategies Pursued Contract Pricing Structures Financial Incentives Utilized Financial Penalties Utilized Top Project Payment Schedule Structures Project Payment Schedule Structures Utilized CRO Performance Metrics Gathered Top Methods of Communication Methods of Communication Utilized
xx 7.50 7.51 7.52 7.53 7.54 7.55 7.56 7.57 7.58 7.59 7.60 7.61 7.62 7.63 7.64 7.65 7.66 7.67 7.68 7.69 7.70 7.71 7.72 7.73 7.74 E-Diaries Market Estimate E-Diaries Uptake Estimate Technologies To Capture Clinical E-diary Data Phases I-III Compliance: Paper v Electronic Diaries Increased Compliance=Increased Quality of Results=Easier Trial Conduct Ediaries Major Players Clinical Trial Laboratory Services Market Share $1.6 billion in 2005 Central Lab Services for Clinical Trials 2004 Total 2005 Revenue from Companies with Central Laboratory Services Pharmaceutical Outsourcing Penetration Paper vs EDC cost comparison Total Active IRBs IRBs active in the U.S. OHRP-Registered IRBs IRBs at Medical Centers Major Medical Centers with the Highest Number of Active IRBs IRBs by Location States with the Highest Number of Active IRBs Molecular Imaging Market Various Techniques Molecular Imaging Market Estimated total Sales 2004-2009 EHR Uptake by Practice Size Top 5 benefits of EHR Top 5 barriers to implementing EHR Patient Experience With New Medical Technologies Select EHR Providers Estimated EHR Market Growth 2005-2015 Call Center Patient Recruitment Services Estimated Total US Market Biopharma Companies Recruiting Online 8.01 8.02 8.03 8.04 Clinical Investigators Number of Investigators submitting INDs Clinical Investigators U.S. vs Non-U.S. Investigators submitting INDs First Time Investigators 1980-2006 First Time Investigators By origin, 1980-2006
xxi 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 8.16 8.17 8.18 8.19 8.20 8.21 8.22 8.23 8.24 8.25 8.26 8.27 8.28 8.29 8.30 8.31 Investigators Filing One Form 1572 Only More Investigators, Lots More Studies All U.S. INDs More Investigators, Lots More Studies All U.S. Investigators More Investigators, Lots More Studies Non- U.S. Investigators Profile of Investigators Filing FDA-1572 Physicians Participating in Clinical Trials Percentage of Surveyed Physicians with Clinical Trial Experience Aging Investigators NIH Traditional Grant Recipients by Age, 1980-2006 Medical School Graduates by Race and Ethnicity 1980-2004 Physician Participation in Clinical Trials Number of Trials Participated in Physician Inclination to Participate in Another Trial Why or Why not Participate Never participated Why or Why not Participate Again Have participated Referring Patients Into Alternate Investigator's Clinical Trials Referring Patients Into Alternate Investigator's Clinical Trials Prior v. Non-Prior Reasons Physicians Don t Refer Patients Into Trials All Reasons Physicians Don t Refer Patients Into Trials Prior Reasons Physicians Don t Refer Patients Into Trials Non-Prior What Would Increase Level Of Comfort To Refer Patients Prior What Would Increase Level Of Comfort To Refer Patients Non Prior Clinical Research Personnel Distribution of Personnel by Specialty 2005 R & D Personnel U.S. Clinical Research Professionals Total Number of Clinical Researchers, by Employment Type U.S. Investigator Profile Most Are Full-Time Researchers European Investigator Profile Most Are Part-Time Researchers Latin American Investigator Profile Most Are Part-Time Researchers European Study Coordinators Percent of Sites Employing a Study Coordinator
xxii 8.32 8.33 8.34 8.35 8.36 8.37 8.38 8.39 8.40 8.41 8.42 8.43 8.44 8.45 8.46 8.47 8.48 8.49 8.50 8.51 8.52 8.53 8.54 8.55 8.56 8.57 8.58 8.59 8.60 Investigator Productivity Number of Studies Conducted Per Investigator Full-Time Coordinators: Distribution of Sites by Number of Full-Time CRCs CRC Productivity 2001 v. 2004 Distribution of Full-Time Coordinators Distribution of Part-Time Coordinators Patient Recruitment Specialist Distribution Patient Recruitment Specialists Comparing Productivity Average Number of Industry-sponsored Trials Conducted per position Comparing Productivity Average Number of Industry-sponsored Trials Conducted per position A Need for More Clinical Investigator Training Primary Training Sources For Investigators Biggest Challenges to Conducting Clinical Trials Latin America Study Conduct Latin America Training Latin America Who Provided Training? Latin America Meeting type preference Live Meetings Most Valuable at meetings Least Valuable at meetings Do you typically attend the study start up meeting? Protocol Training Preferred Learning Methods Remote Meetings: Positives Remote Meetings: Negatives Who Attends Investigator Meetings Novel Approaches to Investigator Meetings Percent Receiving Formal Training in Clinical Trials (Based on number of trials participated in) What type of training did you receive? Was the training adequate?
xxiii 8.61 8.62 8.63 8.64 8.65 8.66 8.67 8.68 8.69 What factor would have the most impact on your decision to leave your current job? In what year were you first required to use EDC? What is the percentage of trials at your site that uses EDC? What type of EDC have you used at your site? What type of company has trained you on EDC? Has the effectiveness of your EDC training over the course of your career: What other type of training do you feel is essential to do your job? What is the top factor that contributes to delays in the conduct of your trials at your site? How many companies have trained you on EDC? 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 9.15 9.16 9.17 Health Related Internet Browsing Individuals using the Internet to Find Health Related Information Trial Information Distribution How U.S. Patients Learn About Trials Finding Health Information Types of Online Health Information Portals Used by Patients Trial Information Distribution Helping Patients Understand Research Risk May Impact Participation Patient Involvement in Their Treatment Ways in which Patients Supplement Their Doctor s Efforts Participation in Pediatric Studies Factors Impacting Willingness Real Fees per Patient Average Fees Paid U.S. vs. E.U. Race/Ethnicity Subgroup Representation in Clinical Trials Volunteer Education Levels What Language Do You Speak At Home? How Many Studies Participated In Most Frequent Illness Addressed How Did You First Contact The Study Center Promptness of Study Staff Reply How Long was the Study? How Many Visits Were Required For The Study
xxiv 9.18 9.19 9.20 9.21 9.22 9.23 9.24 9.25 9.26 9.27 9.28 9.29 9.30 9.31 9.32 9.33 9.34 9.35 9.36 9.37 9.38 9.39 9.40 9.41 9.42 9.43 9.44 9.45 9.46 9.47 9.48 Awareness Of Clinical Trials Prior To Learning Of The Study Factors Impacting Study Participation Factors Reducing Volunteer Willingness to Participate Deciding to Participate in Trials Study Participation Concerns Physicians Ability To Guide Patients To Additional Information on Trials Compensation For Participation Patient Support Type Of Support Received Initial Visit Informed Consent Understanding Study Expectations Understanding Study Expectations Understanding Study Expectations Placebo Understanding Study Expectations Understanding Study Expectations Understanding Study Expectations Volunteer Satisfaction with Efficacy of Care Dropping out of the Study Reasons Volunteer Satisfaction with Quality of Care in Trials Favorable Volunteer Experiences Family Referrals Clinical Trial Participation Estimated Total Participants by Country, 2003 Average Number of Patients Per NDA Number of Evaluable Patients Types of Trials Paying Subjects Phases of Trials Paying Subjects Payment Based on Size of Trial Was Payment Prorated? Institutional Policy Regarding Payment
xxv 9.49 9.50 9.51 9.52 9.53 9.54 9.55 9.56 9.57 9.58 9.59 9.60 9.61 9.62 9.63 9.64 9.65 9.66 9.67 9.68 9.69 9.70 9.71 9.72 9.73 9.74 9.75 Factors Influencing Decision not to Pay Subjects Factors Influencing Amounts of Payments Offered Would Recruitment Have Been Easier with Payment? Recruitment Would Have Been Easier if they Had Offered More Payment Minority Participation in Clinical Trials Enrollment by Sex 2003-2004 Protocols Exclusive to Sex 2003-2004 How Interested Are You in the Results of New Health Research Studies? Which of the Following Reasons Did You Have for not Participating? How Did You Feel about Participating in this Health Research Study? Opinions on Privacy Protection in Medical Studies What are the main reasons for not wanting to give advance general consent or to have your information used without a consent? I Trust My Health Care Providers To Protect The Privacy Of My Personal Medical Records Health Researchers Can Generally Be Trusted To Protect The Privacy Of Medical Records The Privacy Of Personal Medical Records Is Not Well Protected Today By Laws And Practices I still worry about a professional health researcher seeing my medical records Cancer Incidence by Race/ethnicity and Sex, 2002 Prostate Cancer by Race/ethnicity, 2002 Breast Cancer by Race/ethnicity, 2002 Cervical Cancer by Race/ethnicity, 2002 HIV/AIDS Distribution by Race/ethnicity, 1999-2003 Pancreatic Cancer Incidence by Race/ethnicity and Sex, 2002 Lung Cancer by Race/ethnicity and Sex, 2002 Diabetes Incidence By Race/ethnicity, 2002 U.S. Population Without Health Insurance 2004 and 2005 U.S. Population Without Health Insurance by Income Level, 2004 and 2005 Projected Change in US Population Mix 2004-2030
xxvi 9.76 9.77 9.78 9.79 9.80 9.81 9.82 9.83 9.84 9.85 National Health Expenditures and Their Share of Gross Domestic Product 1980-2015(Projected) US Pharmaceutical Spending Growth vs Total Healthcare Spending Growth 2001-2005 Growth in Prescription Drug Spending 1980-2011 Overall Consumer Price Index (CPI) and Medical-Specific Consumer Price Index (MCPI) 1993-2005 Source of Prescription Drugs Expenditures 1965-2004 Number of People Employed in Health Care 1991-2005 Health Care Expenditure as a Percent of Income 2004 Health Care Expenditure by Age Group 2004 Top Therapeutic Categories Contributing to Drug Expenditures 2006 The Five Most Costly Conditions in the U.S. 1997 and 2002 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 10.12 10.13 10.14 10.15 10.16 10.17 10.18 Annual NDAs Total NDA Submissions and Approvals, 2001-2006 Annual NDAs Total NDA Approvals, 2001-2007 NDAs Approved by Review Status First Action by FDA All NDAs, Fiscal Year Cohorts First Action by FDA Priority NDAs, Fiscal Year Cohorts First Action by FDA Standard NDAs, Fiscal Year Cohorts NDA Approvals and Post-Marketing Commitments 2001-2006 NDA Approvals by Chemical Type 2006 NDA Approvals by Chemical Type 2002-2006 New Biologic Approvals 2002-2006 Annual NMEs Total NME Approvals, 2001-2007 Percent of NCEs/NASs first Launched in U.S. 1980-2004 by PDUFA cohort Generic Submissions and Approvals 2001-2006 Total Original IND Submissions Commercial and Non-Commercial IND Submissions Original Commercial INDs, by Year ectd Submissions Submissions as of Date FDA Orphan Drug Designations FDA Orphan Drug Approvals
xxvii 10.19 10.20 10.21 10.22 10.23 10.24 10.25 10.26 10.27 10.28 10.29 10.30 10.31 10.32 10.33 10.34 10.35 10.36 10.37 10.38 10.39 10.40 10.41 FDA Orphan Drug Designations By Therapeutic Area, 2005 FDA Orphan Drug Designations Designations Granted by Therapeutic Area, 2000-2005 FDA Fast Track Designations Outcome of Fast Track applications, 1998-2006 FDA Fast Track Designations Designations Granted by Therapeutic Area Accelerated NDA Review NDAs Receiving Priority or Orphan Status, 2002-2006 Accelerated NME Review NMEs Receiving Priority or Orphan Status, by Year Priority Review Status Priority Review designations by Therapeutic Area, 2004 Priority NDA/BLA Approval Rates Percentage Approved per 6-Month Interval, by Year of Submission Standard NDA/BLA Approval Rates Percentage Approved per 6- Month Interval, by Year of Submission NMEs and Domestic R&D Expenditure 1999-2006 NME Approvals by 3-Year Cohort 1991-2005 Generic Approval Times Median Time to Approval, 1996-2006 Average Exclusivity for Newly Launched Drugs IDE Filings Submission Outcomes 2001-2004 IDE Submissions Total Submissions Received by Filing type, 2001-2005 IDE Decision Times Average Time from Filing to Decision, 2001-2005 HDE Filings Submission Outcomes, 2001-2004 HDE Applications Total Submissions Received by Filing Type, 2001-2005 HDE Approval Times Average Time from Filing to Final Action, 2001-2004 510(k) Classifications Submission Outcomes, FY2001-FY2005 510(k) Submissions Total Submissions Received, 2001-2005 Non-Equivalent 510(k) Approval Times Average Time from Filing to Final Action, 2001-2004 PMA Filings Submission Outcomes, 2001-2005
xxviii 10.42 10.43 10.44 10.45 10.46 10.47 10.48 10.49 10.50 10.51 10.52 10.53 10.54 10.55 10.56 10.57 10.58 10.59 10.60 10.61 10.62 10.63 10.64 10.65 PMA Applications Total Submissions Received by Filing Type, 2001-2005 PMA Approval Times Average Time from Filing to Final Action, 2001-2004 FDA Site Inspections Site Inspections by Target, 2001-2006 FDA Site Inspections Site Inspections Worldwide by Outcome, 2002-2006 FDA Site Inspections Most Common Citations by Type, 2002-2006 FDA Site Inspections Common Citations by Type, 2002-2006 FDA Site Inspections % Site Inspections for Investigator Conduct 1998-2006 Resulting Actions From FDA Inspections Data by Country, 2000-2006 International Clinical Investigator Inspections FY 2002-2006 Location of International Inspections 1980-2006 (n=727) Investigator Disqualifications Number of Disqualifications from CDER/CBER, 2002-2006 Responsibility for Compliance Failure Who Investigators Believe is Responsible for Compliance Failure FDA Public Health Advisories Safety Warnings Issued for Approved Drugs, 2004 FDA Public Health Advisories Safety Warnings Issued for Approved Drugs, 2005 FDA Public Health Advisories Safety Warnings Issued for Approved Drugs, 2006 Approved Drugs Withdrawn from Market 1980-2005 Top 10 Drug Classes Impacted by Medicare Part D Status of Open Postmarketing Commitments Adverse Event Reporting FDA Biomonitoring Inspections with Site Visits FY 2000- FY 2005 Resulting Actions From FDA Inspections Data by Country, 1980-2005 Resulting Actions From FDA Inspections Data by Country, 1980-2005 PDUFA fees collected Process For FDA Review Of Human Drug Applications Total Costs 11.01 Ongoing Clinical Trials Estimated Phase I Trials, 2007
xxix 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 11.11 11.12 11.13 11.14 11.15 11.16 11.17 11.18 11.19 11.20 11.21 11.22 11.23 11.24 11.25 11.26 11.27 11.28 11.29 11.30 Ongoing Clinical Trials Estimated Phase II Trials, 2007 Ongoing Clinical Trials Estimated Phase III Trials, 2007 Ongoing Clinical Trials Estimated Phase IV Trials, 2007 World R&D Market Share PhRMA Member Companies AT Kearney Overall Country Attractiveness Index for Clinical Trials Scale 1-10 International Regulatory Bodies Selected Regulatory Bodies and Filing Names Regulatory Bodies For Selected EU Countries Drug Spending as a Percentage of Total Health Spending 1980-2003 Percent of GDP Spent on Health Care Select Countries, 1980-2004 Source of Prescription Drugs Expenditures 1965-2004 Public v Private Spend on Healthcare Asia Pacific Sources of 1572 filings 2002-2006 Origin of Studies Initiated 2002-2006 Growth of foreign-based studies Clinical Trial Initiations based in FDA-1572, 1990-2006 1572 s by Region 2003-2006 1572 s in Established Regions 2002-2006 1572 s outside North America 2003-2006 1572 s in Ascending Markets As a percentage of all 1572 filings, by year 1572 s by Foreign Country BRIC Countries, 2002-2006 1572 s by Ascending Region 2002-2006 1572 s by Foreign Country Asia Pacific Countries Part 1, 2002-2006 1572 s by Region Asia Pacific Countries Part 2, 2002-2006 1572 s by Top 5 European Countries 2002-2006 US INDs from Select Latin American Countries 2002-2006 Canadian Regulatory Review NDSs Submitted and Approved, 2001-2006 Canadian Regulatory Review NASs* Submitted and Approved, 2001-2006 Canadian Regulatory Review INDSs and CTAs Submitted, 2001-2006 Canadian Regulatory Review CTAs Submitted by Phase, 2001-2006
xxx 11.31 11.32 11.33 11.34 11.35 11.36 11.37 11.38 11.39 11.40 11.41 11.42 11.43 11.44 11.45 11.46 11.47 11.48 11.49 11.50 11.51 11.52 11.53 11.54 11.55 11.56 11.57 Canadian Regulatory Review Priority Review Submissions Approved, 2001-2006 Canadian Regulatory Review Median Time to Approval for Priority and Standard NDSs, 2001-2006 Canadian Regulatory Review Median Time to Approval for Priority and Standard NASs, 2000-2006 NIH Grants to Canada Australian Trials by Phase FY2004/2005 Australian Regulatory Review Estimated Category 1* Applications, 2001/2002-2005/2006 Australian Regulatory Review Orphan Drug Designations Granted NIH Grants to Australia EU Regulatory Review Outcomes for Centralized MAAs, 2001-2006 EU Regulatory Review MAAs Submitted under the Centralized Procedure, 2001-2006 EU Regulatory Review Mutual Recognition Applications, 2001-2006 EU Regulatory Review Orphan Medical Product Designations, 2001-2006 EU Regulatory Review Orphan Designation Review Time, 2001-2006 EU Regulatory Review Orphan Designations, 2001-2006 EU Regulatory Review Mean Centralized MAA Review Times, 2001-2006 NIH Grants to EU Members 2000-2006 Clinical trials approved in Russia Percentage of Clinical Trials conducted by CROs in Russia Russian Patients Enrolled in Clinical Trials Originating Country of International Clinical Trials in Russia Active Phase II-IV Sites East Europe/Russia Registered Trials Emerging Cities Large Market Potential in Asia-Pacific Japanese NDA Approvals FY 2002-2006 Japanese Regulatory Review Priority NDAs Approved Japanese Regulatory Review NCEs Approved, 2001-2005 New Drug Approvals in Japan Conditional vs. non-conditional
xxxi 11.58 11.59 11.60 11.61 11.62 11.63 11.64 11.65 11.66 11.67 11.68 11.69 11.70 11.71 11.72 11.73 11.74 11.75 11.76 11.77 11.78 11.79 11.80 11.81 11.82 11.83 11.84 11.85 New Drug Approvals in Japan Conditional vs. non-conditional clinical development period Japanese Bridging Study Consultations Japanese Bridging Study Approvals Japanese Regulatory Review Initial CTNs submitted for New Chemical Entitles (NCEs), 2001-2005 Clinical Trial Notifications for Drugs Japan Japanese vs. Overseas Approval Years from overseas approval to Japanese approval, New Drugs approved in 2005 Average Time from Initial Global Launch to Start of Marketing Japanese Approvals Accelerating Time from NDA to Approval by Year of Submission, 1993-2003E NIH Grants to Japan Korean Trials Clinical Trials in Taiwan Local vs. Multinational Clinical Trials in Taiwan By Phase Singapore Regulatory Review New Drug Approvals, 2001-2005 Singapore Regulatory Review Clinical Trials Initiated by Phase, 2001-2006 Singapore Regulatory Review Clinical Trials Initiated, 2006 Singapore Biomedical Sciences Employment Growth Number of Clinical Trials in Hong Kong Indian Investigators filing 1572s NIH Grants to India Projected Indian Pharmaceutical Market, 2004-2009 The Indian Clinical Trials Market: An Overview Healthcare Coverage in India by Source Indian Pharmaceutical Market, by Therapeutic Area Latin American Demographics Population Distribution by Age World and Select Latin American Countries Latin American Populations Five Largest Countries Argentine Clinical Trial Protocols Approved 1994-2006 Trial Sponsors in Argentina 1994-2006
xxxii 11.86 11.87 11.88 11.89 11.90 11.91 Argentine Trials by Phase 1994-2006 South African Healthcare Market Estimated Pharmaceutical Use in China 2000-2010 NIH Grants to Foreign Countries Grants to All Research Interests, 2000-2006 International NIH Grant Recipients Top Recipients by Country, 2005 Selecting Countries for Multinational Trials Key Criteria Used by Sponsors