This annual compendium is the leading resource for statistics, trends, and proprietary market intelligence and analyses on the biopharmaceutical industry. Supported by thousands of graphs, illustrations, and analyses, the Sourcebook provides the latest intelligence on every aspect of biopharmaceutical development-from product discovery, to R&D performance and productivity, to time-to-market trends.
With real-world analysis and key contributions from leading consultancies and experts, the Sourcebook includes: •New proprietary analysis on US clinical trial starts, segmented by therapeutic category, as well as overall active clinical trials in the US and globally •Emerging data on worldwide and company-specific R&D pipelines and product launch trends •New analyses on emerging trends in pharma and biotech licensing deals and other partnerships critical to industry's R&D pipeline •Drug approval statistics compiled from FDA, EMA, and other regulatory agencies •New global R&D spending trends and other international R&D data from key markets •International statistics on drug development output •And much more!
Additional new features in the 2014/2015 edition include: •New spotlight analyses on emerging and re-emerging elements of industry's R&D pipeline, including immuno-oncology, antibiotics, and gene therapy •A new analysis of pharma innovation and industry trends and evolution by Bernard Munos, founder of InnoThink and a widely acknowledged visionary on the biopharma industry •An all-new section on market access/reimbursement/drug pricing metrics and trends •New assessments of several emerging industry controversies, including the implications of ultra-rapid new drug reviews and R&D "overcrowding" in some parts of the new drug pipeline •New analyses on the state, nature, and sustainability of industry's pipeline of R&D projects •All new assessments of personalized medicine/companion diagnostics, biosimilars, orphan drugs, and other factors reshaping biopharma R&D today

Section 1: R&D Spending

Pharmaceuticals

Global Pharma and Biotech R&D Expenditures, 2006-2020P (EvaluatePharma) 1

      Global R&D Spending by World's Top 500 Pharma and Biotech Companies, 2006-2020P (EvaluatePharma) 1

R&D Spending by Research Based Pharmaceutical Companies (PhRMA), 1980-2013 2

R&D Investments by Research-Based Pharmaceutical Companies (PhRMA), 1980-2013 2

Industry-wide and Government R&D Spending, 1980-2013 3

      Biopharmaceutical Industry Investment in Research and Development, 1980-2013 3

      Biopharmaceutical R&D Expenditure and NIH Budget: 1995-2013 3

"Decline in U.S. Financial Competitiveness in Biomedical R&D"—New Study 3

5 Questions with Bernard Munos 4

Munos on "Mad Scientists" and "Safer Bets" 7

Top 100 Pharmaceutical Companies by R&D Spending (2013), 2013A-2015P (EvaluatePharma) 8

Analysis of Top 20 Companies by 2013 Pharma R&D Spend (EvaluatePharma) 9

      Top 20 Companies by Pharma R&D Spend in 2013 vs. 2012 (EvaluatePharma) 9

      Top 20 Companies by Pharma R&D Spend as a % of Pharmaceutical Revenues, 2012 vs. 2013 (EvaluatePharma) 9

      Top 20 Companies by Count of Late-Stage Projects (Phase II to Filed) and PDUFA Dates, 2013 9

      Top 20 Companies: Average R&D Spend per Late-Stage Project in 2013 (EvaluatePharma) 10

Total PhRMA R&D as a Percent of Sales, 1997-2013 11

Domestic U.S. R&D and R&D Abroad, 1999-2013 11

Domestic U.S. Sales and Sales Abroad, 1999-2013 11

Growth in Domestic U.S. R&D and R&D Abroad, 1973-2013 12

Various Measures of New Drug/Biologic R&D Productivity, 1995-2013 13

      Industry R&D Spending per NDA Submission in the U.S., 1995-2013 13

      Industry R&D Spending per NDA Approval in U.S, 1996-2012 13

      Industry R&D Spending per NME/NBE Submission to FDA, 1996-2013 13

      Industry R&D Spending per NME/NBE Approved in the U.S., 1996-2013 13

      Global R&D Spending per Global New Active Substance (NAS) Launch, 2002-2013 13

Comparative R&D Spending and Product Launch Trends Worldwide: A 2014 Analysis 14

      Geographic Distribution of PhRMA Member R&D Spend, 2012 14

      Pharmaceutical R&D Expenditure Annual Growth Rate, US vs. Europe, 1994-2013 14

      Pharmaceutical R&D Expenditure in Europe, the United States, and Japan, 1995-2013 15

      Markets of First Launch for 47 New Active Substances Introduced in 2013 15

An Analysis of Global R&D Spending on Clinical Trials, by Phase and by Region, 2002-2020P 16

      The Global Clinical Trials Market: Global R&D Spending on Phase 1-3 Clinical Trials, 2002-2020P 16

      Global R&D Spending by Clinical Trial Phase, 2002-2020P 16

Downturn in Cardiovascular Research Concerns Docs 17

Annual R&D Spending Versus New Drug Approvals, 1992-2013 17

R&D Spending by Geographic Area, Ethical Pharmaceuticals, PhRMA Member Companies, 2012 18

Domestic R&D and R&D Abroad for Human-Use and Veterinary-Use Pharmaceuticals, PhRMA Member Companies, 2012 19

Domestic U.S. Scientific, Professional, and Technical R&D Personnel by R&D Function, Ethical Pharmaceuticals, 2010 19

Domestic R&D by Function, Ethical Pharmaceuticals, PhRMA Member Companies, 2012 19

Domestic R&D by Origin of Product (Licensed-in vs. Self-originated), PhRMA Member Companies, 2010 19

Global R&D Funding Forecast for 2014 20

      Share of Total Global R&D Spending by Country/Region, 2012 to 2014P 20

      Life Science Industry R&D Forecast, U.S. vs. Global, 2011-2014 20

      US-China-EU Annual R&D Spending, 2012-2024 20

U.S. Government (NIH) Funding for Medical/Clinical Research, 1995-2014P 21

NIH Appropriations, 1995-2015P 21

NIH Clinical Research and Clinical Trials Spending, 2005-2014P 21

Estimates of Funding for Selected Diseases, Conditions, and Research Areas, 2011-2014P 21

Various Benchmarks on Proportion of R&D Spending by Stage/Area 22

      Shifts in R&D Spending by Phase, 2010 vs. 2011 vs. 2012 vs. 2014 22

      GlaxoSmithKline R&D Spending by Phase, 2012 vs. 2013 22

      AstraZeneca R&D Investment by Stage: Goals Going Forward, 2013 vs. 2014E 22

      BMS R&D Spend Metrics, 2011-2013 22

      Novartis R&D Spending by Phase, 2012 22

R&D Shifts to Phase 4—New PhRMA Data 22

Pharma R&D to 2016: A 2014 Analysis 23

Industry R&D Spending Bounce Back Slowed in 2013—Annual Booz Study 23

A 2013 Assessment of R&D Costs per Approved Drug/Biologic, 2002-2012 24

Share of Biopharma R&D Spending Estimates by Stage of Development 24

      Estimated R&D Spend Share by Stage of Development 24

      Estimated R&D Spend Share by Phase 24

Top 100 Biotechnology Companies by R&D Spending (2013), 2013A-2015P 25

Top 100 U.S. Biotech Companies by 2013 R&D Spending 26

R&D Spending at Selected Leading Biotechnology Companies, 2013A-2018E 27

Branded Drug Revenues to Rise Only Modestly in 2014—Fitch 27

Fewer Small Public Biotechs Today: A BIO Analysis 28

      Number of Active Public Biotech Companies Trading on U.S. Exchanges, 2008-2013 28

      Number of Public Companies by Size, 2007-2013 28

Biologics and Biotech R&D: An Analysis of PhRMA Member Companies, 2010 28

      Biologics and Biotechnology R&D, PhRMA Member Companies, 2010 28

A May 2014 BIO Analysis on the Profitability of the Public U.S. Biotechs 29

      The Profitable Public U.S. Biotech Companies in 2013 29

Will Bust Follow the Latest Biotech Boom? 29

An Analysis of Global Biologics/Biotech Market: Worldwide Sales for Top Products and Top Product Classes in 2012 30

      Top-Selling Categories of Biologic Products, 2012 30

      Growth Rates of Top-Selling Classes of Biological Products, 2012 30

      Top 20 Selling Biologic Products Worldwide, 2012 30

The State of the Biotech Industry: A 2013 Assessment 31

      Growth in Established Biotechnology Centers, 201 l-12(US$b) 31

      Ernst & Young Survival Index, 2011-2012 31

      U.S. Biotechnology at a Glance, 2011-2012 31

      U.S. Biotechnology: Commercial Leaders and other Companies, 2011-12 32

      European Biotechnology at a Glance, 2011-12 33

      Canadian Biotechnology at a Glance, 2011-12 33

Biotechs Off to Fast Start in 2014—BioWorld 33

Trends in Global Spending on Medicines to 2017 34

      Global Medicines Spending and Growth, 2008-2017 34

      Global Growth in Medicines Spending: Developed Countries, Pharmerging Countries, and Rest of World 34

      Drug Spending by Region and Leading Countries 35

      Geographic Distribution of Medicine Spending, 2012 vs. 2017 35

      Drug Spending by Therapy Area in 2017 36

      The Biologics Market, 2002-2017 37

      Specialty Medicine Spending Between 2012 and 2017 37

      Global Spending on Brand vs. Generic Drugs, 2012 vs. 2017 38

Therapeutic Categories: Drug Sales as a Percentage of Worldwide Market, 2013 vs. 2018P 38

Pharma Companies: Drug Sales as Percentage of Worldwide Market, 2013 vs. 2018P 38

The Amount Americans Spend Annually: Medicines vs. Select Other Products/Services 39

Big Pharma and Big Drugs 39

Big Pharma and the Emerging Market Opportunity: A 2014 Snapshot 40

      Emerging Market Exposure for Select Big Pharma Companies for 2013 40

      Revenue Growth Rates for Select Big Pharma Companies for FY2013: Emerging Markets vs. U.S. vs. ex-US developed ROW 40

An Analysis of Worldwide Prescription and OTC Sales, Conventional Drugs vs. Biotech (2006-2020P) 41

      Worldwide Rx & OTC Sales, Biotech vs. Conventional Technology, 2006-2020 (EvaluatePharma) 41

      Worldwide Prescription & OTC Sales by Technology (Top 100 Drugs), 2006-2020P (EvaluatePharma) 41

An Analysis of the Sales Potential of New Drugs Approved in 2012 and 2013 (EvaluatePharma) 42

      Number of New Drugs Approved, 1998-2013 (EvaluatePharma) 42

      FDA Approval Count vs. 5th Year after Launch US Product Sales, 1998-2013 (EvaluatePharma) 42

      Top 10 New Molecular Entities in 2013: Ranked on US Consensus Sales in 2018 (EvaluatePharma) 42

      Top 10 New Molecular Entities in 2012: Ranked on US Consensus Sales in 2017 (EvaluatePharma) 42

The Global Pharmaceutical Market, 2011 vs. 2020 43

      The Pharmaceutical Market in Growth Markets, 2011 vs. 2020P 43

Generics Accounted for 86% of Prescriptions Filled in 2013—IMS Health 43

An Analysis of Top 20 Companies by Worldwide Prescription Drug Sales in 2012 and 2013 44

Put Your Money in Digital Technology or Pharma R&D? 44

An Analysis of Worldwide Prescription and OTC Drug Sales by Therapy Area, 2013-2020P 45

      WW Rx and OTC Sales by Therapy Area: Top 16 Categories and Total Market, 2010-2020P (EvaluatePharma) 45

U.S. Generic Drug Market Outlook to 2020 45

      2013 U.S. Sales of Drugs Potentially at Risk to Gencrics, 2013-2020 45

      Percent Sales Vulnerable to Patent Expirations Through 2020: Selected Leading Companies 45

Redetining the Blockbuster: Why the $1 Billion Entry Point is No Longer Sufficient 46

      Many Top Blockbusters Going Off Patent by 2016: 2011 Top 20 Product Dynamics 46

      $1B is Worth 1/7th in Terms of Global Market Share Than in Period of First Blockbuster 47

      Only $lBn Blockbusters Show Any Real Growth in Numbers Beyond 2005 47

U.S. OTC Medicine Retail Sales, 2009-2013 48

U.S. OTC Medicine Retail Sales by Category, 2013 48

Learning from the "Miracle" Responders 48

Projected 2014 Pharma and Healthcare Spending Growth by Region 49

Growth in Domestic U.S. Sales and Sales Abroad, Ethical Pharmaceuticals, 1973-2013 50

Sales by Geographic Area, Ethical Pharmaceuticals, PhRMA Member Companies, 2012 51

New Analysis of the Global Pharma Market: Leading Therapy Classes, Products, and Companies in 2013 Sales 52

      Top 20 Therapeutic Classes by Global Prescription Sales, 2013 52

      Top 20 Global Prescription Products by Sales, 2013 52

      Top 20 Global Drug Companies by Sales, 2013 52

U.S. Trends in Medicines Use and Spending: An April 2014 Analysis 53

      2013 Medicines Spending and Growth Segmentation Comparison 53

      Generic Drugs: Percent Share of Dispensed Prescriptions, 2004-2013 53

      Top 20 Therapeutic Classes by Spending, 2009-2013 53

      Top 25 Prescription Medicines by Non-discounted Spending, 2009-2013 54

      Number of On-therapy Patients by Therapy Area, 2013 54

ViiV Has Top Reputation Among Patients Groups—New Survey 54

Orphan Drug Market Trends and Projections to 2018: A 2013 Analysis 55

      Worldwide Orphan Drug Sales & Share of Prescription Drug Market, 1998-2018 55

      Worldwide Orphan and Prescription Drug Sales, 2004-2018 55

      Worldwide Top 30 Selling Orphan Drugs, 2012 vs. 2018P 56

      Worldwide Orphan Drug Sales, 2012 vs. 2018: Top 20 Companies & Total Market 57

Regulatory Affairs Budgets Grow Despite Pharma Budget Cutting 57

      Average Percentage Change in Regulatory Affairs Budgets from 2010-2012 by Company Type 57

An Analysis of Industry Trends Driving Growth in Outsourcing: A 2014 Jefferies Survey 58

      R&D Budget Growth Expectations to 2014E 58

      Percentage of R&D Budget Expected to be Outsourced, 2013-2015 59

      Changes to Outsourcing Strategy During Last Two Years 59

      Anticipated Growth in Outsourced Early- and Late-Stage Spending: Findings from 2013 Survey vs. 2014 Survey 59

      Average Number of CROs Used, 2014 Survey 59

      Types of CROs Used, 2014 Survey 60

      Late-Stage Outsourcing Penetration, 2013-2015 60

R&D Trends Driving the Outsourcing Industry to 2020: A 2014 Assessment 61

      Global CRO Market Model, 2000-2020 61

      Percentage of Total Work Outsourced by Phase, by Company Type 62

A Global CRO Market Model to 2018: A 2014 Analysis 63

      CRO Revenues & CRO Market Penetration, 2004A-2018E 63

      UBS Proprietary CRO Market Model, 2005A-2018E 64

A CRO Market Model to 2017: A November 2013 Analysis 65

Expectation for CRO Market Growth, 2012-2017E 65

Sources of Pharmaceutical Development Funding 65

Where Global Biopharma R&D is Spent by Region/Country 66

R&D Spending Growth Consensus Forecasts, 2013-2015 66

Drug/Biotech Company Use of Strategic Sourcing Models 66

The CRO and Clinical Research Market: An April 2013 Survey 67

      If you ran a global CRO, in which region would you invest most heavily? 67

      If you ran a global CRO, in which country would you invest most heavily? 68

      If you ran a global CRO, in which R&D phase would you invest most heavily? 68

      Percent of R&D Budget Outsourced 69

UCB Offers $ 10,000 Reward for Superwoman or Superman 69

A CRO Market Model to 2017 70

      Historical CRO Market Estimates, 1993-2012 70

      CRO Outsourcing Model, 2012-2017E 71

      Clinical Trials by Location 72

Section 2: Products in Development

Pharmaceuticals

Worldwide Drugs in the Pipeline by Therapeutic Category as of January 2014 (IMS Health) 73

Top 50 Drug Companies by Number of Drug Products in Development as of January 2014 (IMS Health) 74

Top 50 Drug Companies by Number of Drug Products in Development as of January 2014 (Citeline, Inc.) 75

A Snapshot of the Pharma R&D Pipeline, Number of Projects by Development Phase, 2002-2014 76

      Worldwide Active R&D Projects in Development by Stage, 2002-2014 76

      The R&D Pipeline, 1998-2014 76

An Analysis of the Drug and Biotech Pipeline by Development Phase, Technology, Therapeutic Category, and Strategy (EvaluatePharma), May 2014 77

      R&D Project Count by Current Phase (EvaluatePharma) 77

      R&D Project Count by Technology (EvaluatePharma) 77

      R&D Project Count by Therapy Area (EvaluatePharma) 77

      R&D Project Count by Strategy (EvaluatePharma) 77

An Analysis of New Clinical Trial Starts for Drugs as Measured by Commercial IND Submissions to FDA, 2013 78

      New FDA-Regulated Clinical Trial Starts for Drugs and Biologics/Biotechs, 2000-2013 78

      Breakdown of CDER Divisional Workload by INDs Received in 2013 78

      Segmentation of US Clinical Trial Starts for Drugs by Therapeutic Category, 2011-2013 79

Heart Research Not Keeping Pace 79

An Analysis of Clinical Trials Started Globally in 2013 by Therapeutic Area, Disease, and Company 80

      Clinical Trials Started in 2013, by Therapeutic Area 80

      Top Ten Diseases for Which Trials Involving Unapproved Drugs Started in 2013 80

      Top Sponsors for Trials Started in 2013 by Therapeutic Area 80

Top Therapy Areas and Diseases by Number of Projects in Development as of January 2014 81

      Pipeline by Therapeutic Group, 2013-2014 81

      Top 25 Therapeutic Categories by Number of R&D Products 81

      Top 25 Disease Indications by Number of Active Compounds 82

      Top 25 Origins of Pipeline Drugs 82

      Top 25 Mechanisms of Action (Pharmacology) 83

      Top 25 Drug Protein Targets 83

Global New Active Substance Product Launches, 2000-2013 84

An Analysis of FDA-Regulated Clinical Trial Activity for Drugs as Measured by Active INDs at Year-End 2013 85

      Breakdown of CDER Drug Divisions' IND Review Workload (Active as of Year-End 2013) 85

      Segmentation of FDA-Regulated Clinical Trials for Drugs by Therapeutic Category, 2013 85

The R&D Pipeline: A 2014 Assessment 86

      Drugs in Active Development, 1995-2014 86

      Drug Development by World Status, 1998-2014 86

Proportion of Top Pharma and Biotech Company Pipelines In-licensed: A 2014 Assessment 87

      Leading Pharma Companies by Pipeline Size: Percent of Pipelines In-licensed, 2009-2014 87

      Selected Leading Biotech Companies by Pipeline Size: Percent of Pipelines In-Licensed, 2009-2014 87

The R&D Productivity Crisis: A 2013 Analysis 88

      Number of New Molecular Entities/Biologics Approved per $lbn Spent, 1970-2012 88

      Average Global Revenues Five Years from FDA Approval, 2000-2013YTD 89

      NME/BLA Launch Delivery 89

      R&D Projects by Therapy Area 89

      Over-concentration of R&D in Oncology 89

      Over-concentration of R&D in Rheumatoid Arthritis 90

The Biggest Projected Drug/Biologic Launches in 2014 (EvaluatePharma) 90

      Biggest Expected Launches of 2014: Biotech vs. Conventional Products (EvaluatePharma) 90

      Biggest Launches of 2014 by Therapy Area 92

      Fifth Year of All Launches per Year 92

      Percentage of Projected Top Ten Launches That Made It to Market on Time, 2008-2013 92

      Progress of Biggest Products Forecast to Have Launched in 2013 93

New Approach to Measuring Drug Innovation Finds Truly Innovative New Drugs Reaching Patients at Fairly Constant Rate 94

      Selected Findings from FDA Drug Innovation Study 95

Azheimer's: What is the Target? 95

Is Alzheimer's Rate Falling Globally? 95

Therapeutic Area Spotlight: Immuno-Oncology 96

      Global Anli-PD-1 Market—Base Case, 2015-2022 96

      Selected Immuno-oncology Therapies in Development 96

      BMS' Andreotti on Balancing the Potential Opportunities and Pitfalls of Immuno-Oncology 97

Innovation in Cancer: A May 2014 Assessment 98

      Metrics on Oncology Products in the R&D Pipeline 98

      Oncology NMEs Launched Globally, 2004-2013: Biologics vs. Non-Biologics 99

      Phase III Trials by Cancer Type and 5-year Disease Prevalence 99

R&D Trends and Drug Launches, 2000-2012: Oncology, CNS, and Cardiovascular 100

      NAS Launches in Oncology, 2000-2012 100

      NAS Launches in CNS, 2000-2012 101

      NAS Launches in Cardiovascular, 2000-2012 101

Measures of Pharma Industry's New Drug Output: NME/NAS Submissions to FDA and EMA, 1996-2013 102

Top 20 Most Valuable R&D Projects, 2014 (Ranked by Net Present Value) 103

Valuing Company R&D Pipelines Based on NPV Analysis: Top 20 R&D Spenders in 2013 104

      Valuing the R&D Pipeline: Pipeline NPV Minus Pharma R&D in 2013 104

Measures of Diversity and Novelty of Drug Targets in Active R&D Projects, 1995-2014 105

      Target Diversity: Number of Protein Targets Under Study in R&D Projects, 1995-2014 105

      Percentage of Products Involving "Unproven" Targets, by Phase 105

2017 Sales Potential of Top New Drug Candidates of 2014 105

      Top 20 Projected New Drugs of 2014 Based on 2018 Sales Potential 105

The Innovativeness of the 2013 NME Approvals 106

      The Approval Rebound Begins: ICTs vs. "Other" Drugs Approved, 1997-2013 106

First-in-Class vs. Best-in-Class: Which Is More Important to Commercial Success? 107

A Closer Look at FDA's 2013 New Drug/Biologic Approvals 108

      NME and NBE Submissions to CDER, 2004-2013 108

      CDER First-in-Class Medicines Approved, 2011-2013 108

      Prevalence of Orphan Drugs in CDER's NME/NBE Approvals, 2001-2013 108

Various New Studies Assess the Origins of New Drugs 109

      Innovation: 59% of 39 New Drugs Approved by FDA in 2012 from Outside Large Pharma Companies 109

      Innovation: 48% of 27 New Drugs Approved by FDA in 2013 from Outside Large Pharma Companies 109

The FDA's New Drug Approvals of 2013: A Trends Analysis 110

      Estimated Peak Sales Potential of New Drugs Approved by FDA, 2010-2013 110

      Number of New Potential Blockbusters and Average Estimated Peak Sales for NMEs, 2010-2013 110

      Number of Therapeutic NMEs Approved by Indication 110

      New Drugs Approved by FDA 2003-2012by Size of Drug Sponsor 111

      FDA New Drug Approvals by Location/Headquarters of Drug Sponsor/Owner, 2003-2013 111

      Companies with Highest Peak Sales Estimates/Most FDA New Drug Approvals, 2009-2013 111

      Therapeutic NME Approvals: In-Hpuse Development, In-Licensed, or Acquired Through M&A, 2003-2013 111

A Renaissance for the Antibiotic Pipeline?: An April 2014 Analysis 112

      Number of FDA New Antibacterial Drug Approvals, 1984-2013 112

Gene Therapy Slowly Rising from the Ashes?: A 2014 Analysis 113

      Clinical-stage Gene Therapy Projects for Rare, Inherited Disorders 113

BCG Perspectives on Biomarkers and Personalized Medicine: Not Just for Specialty Care Drug Development 115

      Promising Diabetes Treatments are in the Pipeline, but a Cure is Unlikely for Some Time 115

      Researchers Are Racing to Identify New Diabetes Biomarkers; Scientific Publications by year, 2004-2012 116

International Effort to Attack Alzheimer's 117

Novartis Undertakes "Portfolio Transformation," Reshapes Itself for New Growth Phase 118

      The Novartis Molecular Pathways Approach 119

      New Chemical/Molecular Enlity Approvals for Selected Companies, 2007-2013 119

      Novartis Anticipated Clinical, Submission, and Approval Milestones through November 2015 119

      Novartis Clinical Pipeline by Phase and Therapeutic Area 119

Pfizer Enters 2014 with New Structure 120

      Pfizer's New Business Structure 120

      The Pfizer R&D Pipeline, 2014 121

      The Pfizer Clinical Pipeline by Indication and Phase, 2014 122

Lilly Looks to New Approvals, Growing Pipeline to Return to Sustained Growth Post-2014 122

      Lilly Phase 2, Phase 3, and Registrations! Pipeline, October 2004 vs. September 2013 123

      The Lilly Clinical Pipeline by Indication, 2014 123

      Lilly's Timely Value Medicines Approach to Patients (TVM) Attributes 124

Merck Revamps Operating Model, Sharpens Commercial and R&D Focus Post-Singulair 125

      Merck's New Strategic Initiative to Increase Focus and Reduce Costs by $2.5B in 2015 125

      Merck's Geographic and R&D Priorities 125

      Advancing the Innovative Pipeline: Merck's Four Potential Future Growth Drivers 126

      Merck's Development Projects by Indication and Phase, March 2014 127

Roche Leverages Oncology and Personalized Medicine, Re-aligns Some R&D Efforts 127

      Roche Strategy: Leveraging Pharmaceuticals and Diagnostics 128

      Roche's R&D Investments in Key Areas: Recent Trends 129

      Select Roche/Genentech Pipeline Metrics: Five Years On 129

      Roche's Clinical Development Pipeline Projects by Therapeutic Area, January 2014 129

      The Roche Group's R&D Structure and Approach 129

AstraZeneca Builds Momentum, Continues Toward Return to Growth 130

      AstraZeneca's "Journey," 2013-2020 130

      AslraZeneca's Phase 3 Pipeline Size: Plan vs. Actual, 2012-2016 131

      AstraZeneca's NME Clinical Pipeline by Therapeutic Area, January 2014 131

GlaxoSmithKline Heralds Productive R&D Output, Accelerates Strategy for Growth 132

      NME Approvals at Selected Big Pharmas, 2008-2013 132

      GSK's "Global Leadership" and "Challenger" Businesses 133

      GSK's "Pipeline Opportunity" in 2014 133

      The GSK Clinical Pipeline by Phase and Disease Area, March 2014 133

Bristol-Myers Squibb Doubles Down on Immuno-Oncology and Pipeline 134

      Evolution of BMS BioPharma Strategy 134

      The BMS Pipeline by Development Phase and Disease, March 2014 135

      The BMS Immuno-Oncology Clinical Development Pipeline 135

Will the Blockbuster Model be Replaced?: The Rare Disease Landscape, 2013 136

      Rare Disease Drugs in Development, by Phase 136

      Rare Disease Drugs in Development by Therapeutic Area 136

      Rare Cancer Diseases with Ten or More Active Drugs in Development 137

      Rare Diseases with 10+ Drugs in Active Development (Outside Cancer and Infectious Diseases) 137

An Assessment of Orphan Drugs in the US: A 2013 Analysis 138

      Fate of Drug Candidates after Orphan Designation 138

      Orphan vs. Non-Orphan Drugs: By the Numbers 138

      Current Phase of Orphan Drugs vs. Current Phase of All BMT Drugs 139

      Molecule Type of Drugs with Orphan Designation vs. All BMT Drugs 139

      Phase of Drugs at Orphan Designation 140

      Probability of Technical Success (PTS) for Non-Oncology Drugs 140

      Probability of Technical Success for Oncology Orphan and Non-orphan Indications 141

      Probability of Technical Success for Oncology Drugs With and Without Orphan Designation 141

Top 25 Most Researched Rare Diseases 141

      Pharma/Biotech Dealmaking: An Analysis of Activity in 2013 142

      Top 10 Dealmakers in 2013 142

      Partnership Deals: Volume Distribution Across Trial Phases, 2011, 2012, and 2013 142

      Biotech and Pharma Deals by Volume Across Therapy Areas, 2013 142

      Number of Deals Involving Large vs. Small Molecules, 2012 vs. 2013 142

      Academic Deals—Total Number, 2007-2013 143

      Academic Deals—Total Deal Values, 2007-2013 143

Big Pharma's M&A "Firepower" Declines—E&Y Report 143

Royalty Rate Opportunities in Pharma Licensing: A 2013 Analysis of Average Royalty Rates in Pharma by Phase and Therapeutic Area 144

      Royalty Rates by Phase at Deal Signing—Last Five Years 144

      Royalty Rate Distribution by Phase at Deal Signing 144

      Royalty Rates by Therapy Area—Last Five Years 145

      Royalty Rate Distribution by Therapeutic Category 145

Source of Late-Stage Pipeline Valuation for 12 Leading Companies: A 2013 Analysis 146

      Source of Late-Stage Pipeline Valuation, 2010-2013 146

      External Component of Late-Stage Pipeline Valuation, 2010-13 146

Is RNAi DOA? 146

Active Clinical Drug Development Programs Worldwide by Phase, April 2014 147

      Number of Active Clinical Development Programs, 2014 147

      Total Average Number of Active Programs by Year, March 2004-April 2014 147

      Comparison of Annual Growth Rate—2009 vs. 2010 vs. 2011 vs. 2012 vs. 2013 vs. 2014 147

Number of Companies in Pharma R&D Continues to Rise, 1998-2014 148

      Number of Companies with Active Product Development Projects, 1998-2014 148

      Distribution of R&D Companies by Country/Region, 2014 and 2013 148

Growth in the Number of Compounds in Development: A 2014 Assessment 149

      Estimated Number of Drug Candidates in Each Stage of Development, 2009-2014 149

PhRMA's Medicines in Clinical Development Series 150

      Analysis of Drugs in Clinical Development for Parkinson's Disease, 2014 150

      Analysis of Drugs in Clinical Development for Diabetes and Related Conditions, 2014 150

      Analysis of Drugs in Clinical Development for Diseases of Aging, 2013 150

      Analysis of Drugs in Development to Treat Rare Illnesses, 2013 150

      Analysis of Drugs and Vaccines in Clinical Development for Infectious Diseases, 2013 150

      Analysis of Drugs in Development for Heart Disease and Stroke, 2013 151

      Analysis of Drugs in Development for Leukemia, Lymphoma, and Other Blood Cancers, 2013 151

      Analysis of Drugs in Development for Alzheimer's Disease, 2013 151

      Analysis of Drugs in Development for Neurological Disorders by Development Status and Indication, 2008 151

      Analysis of Drugs in Clinical Development to Treat Mental Illnesses and Addictive Disorders, 2012 151

      Analysis of Drugs in Clinical Development for Cancer by Development Status and Indication, 2012 152

      Analysis of Drugs in Clinical Development for Chronic Obstructive Pulmonary Disease, 2012 152

      Analysis of Drugs in Clinical Development to Treat Asthma, 2012 152

      Analysis of Drugs in Clinical Development to Treat Pediatric Illnesses, 2012 152

      Analysis of Drugs in Development for AIDS and AIDS Related Illnesses, 2012 152

      Analysis of Drugs in Development for Skin Diseases, 2011 152

      Analysis of Drugs in Clinical Development for Arthritis, 2011 153

      Analysis of Drugs in Clinical Development for Women by Development Status and Indication, 2011 153

Top Therapeutic Drug Categories Worldwide by Number of Projects in Development as of January 2014 153

Number of Drugs in Preclinical Testing, 1995-2014 153

Development Pipelines of Selected Leading Drug Companies: Number of Products by Stage of Development, March 2014 154

Redefining Biopharma Innovation in the Era of Health Care Reform 155

      Innovation Explored: Innovation in Diabetes Treatment 156

      2011 NDA Approval Analysis 157

      Approvals by Molecule Type, 2007-2011 157

      Innovation by TA, 2009-2011 157

      Probability of Success (POS) at Key Milestones by Therapeutic Area 158

Biosimilars: Various Assessments of the Market, Costs, Prices, and Pipeline 159

      Global Biologics Spending: Biosimilars and Other Biologics, 2002-2017 159

      The Biosimilars Clinical Pipeline by Phase, April 2014 160

Global Oncology Biosimilars Market to $6B-$ I2B by 2020: IMS Health 160

Biosimilars: Small Victories, Big Challenge 161

From the Biosimilar Battlefield: The Rituxan Wars 162

Disclosed Biosimilars Pipeline Swells: Decision Resources 162

The Biosimilars Development Pipeline and U.S. Market Evolution: A 2014 Assessment 163

      Reference Products with Patents Extending After Other Exclusivities 163

      U.S. Biosimilar Launchable Dates, 2012-2024 164

      Biosimilars/Biobetters Universe by Class 164

      Numbers of Biosimilar or Biobetter Candidates Targeting Reference Products and Classes 164

      Biosimilars and Biobetters by Stage of Development 164

      Biosimilar and Biobetter Development by Country/Region of Developer 165

      Companies With the Largest Biosimilars Development Portfolios 165

      Companies Developing Biosimilars or Biobetters, by Annual Revenue 165

Lilly's Lechleitcr: Dismissal of Incremental Therapeutic Gains Troubling 166

Biosimilar Monoclonal Antibodies in Development: A 2012 Analysis 167

      Companies with Two or More Biosimilar mAbs in Development 167

      Disease Indications for Biosimilar mAbs Currently in Clinical Trials 167

      Top Locations for Biosimilar Trials 168

"Printing" Drug Dosages Tailored to Individual Patients 168

Development Pipelines of Selected Leading Pharmaceutical Companies by Phase and Therapeutic Area, March 2014 169

More Concern Over Primary Care Not Being a Primary Focus 169

Biotechnology Products as a Percentage of Total R&D Pipeline (EvaluatePharma®), May 2014 170

      R&D Project Count by Technology 170

Pharma Innovation: Big Company, Small Company 170

The Breadth of Unmet Medical Needs Today 170

New Clinical Trial to Place Subjects in "Suspended Animation" 170

The Biotech Product Pipeline within Big Pharma: A 2013 Analysis 171

      Biologics in Clinical Development, 2001-2012 171

      Global Revenue for Biotech Products, 2002 2012 171

      Biological Products in Development at Pharmaceutical Companies by Product Type, 2012 172

      Number of Biological Products in Development at Pharma Companies by Therapeutic Area, 2012 172

      Pharma Company Acquisitions of Biotech Companies, 1998-2012 172

Will Big Pharma's "Narrower Therapeutic Base" Make It More Vulnerable? 172

The Biotech Bull Market, IPOs, and Dealmaking 173

      Number of Biotech IPO Listings in the U.S., 2013-2014 173

      Big Biotechs Offering Competitive Valuations in R&D-Stage Deals 173

      Big U.S. Biotech vs. Big U.S. Pharma: R&D Spend and Cash, 2013 173

What Does the Market Value More: Making, Buying, or Allying? 173

The Pipeline for Monoclonal Antibodies: A 2014 Assessment 174

      Therapeutic mAbs in Development by Phase, 1995-2014 174

      Number of Monoclonal Antibody Therapies in Development by Subtype, 1995-2014 174

Analysis of Vaccines in Development, 2013 175

      Vaccines in Development by Clinical Phase and Product Class 175

Analysis of Biotechnology Medicines and Vaccines in U.S. Clinical Development by Development Status and Therapeutic Category, 2013 175

      Biotechnology Drugs and Vaccines in Development by Product Type, 2013 175

Monoclonal Antibodies in the Global Development Pipeline: A December 2011 Analysis 176

      New mAbs Entering Into Clinical Development, 1997-2010 176

      Total mAbs in the Pipeline by Phase 176

      Modified mAbs in the Pipeline 176

      FDA-Approved mAbs by Therapeutic Area/Indication, 1997-2011P 176

      Average Clinical and FDA Approval Phase Lengths for Marketed mAbs 177

      Phase Transition Rates for Humanized mAbs 177

Biotech Company Development Pipelines: Number of Development Projects by Phase of Development, March 2014 177

Development Project Pipelines for Selected Leading Biotech Companies by Therapeutic Categories and Phases, March 2014 178

The Monoclonal Antibody Pipeline, 2012 179

The U.S. and European Biotech Clinical Pipeline: A 2013 Assessment 180

      US biotech clinical pipeline by indication, 2012 180

      US biotech Phase III pipeline by indication, 2012 180

      European biotech pipeline by year, 2012 vs. 2011 180

      European clinical pipeline by indication 180

Innovation in the Biopharmaceutical Pipeline: A 2013 Multidimensional Analysis 181

      Distribution of Products and Projects by Phase 181

      Distribution of Products and Projects by Therapeutic Area and Phase 182

      Potential First-in-Class Medicines in Development, by Phase 183

      Potential First-in-Class Medicines in Development, by Therapeutic Area 184

      Projects for Selected Diseases and Conditions with No Approvals in Ten Years 185

      Personalized Medicine Trials by Condition and Therapeutic Area, 1993-2008 185

      Selected Breakthrough Scientific Strategies: Number of Projects by Phase 186

The Drug/Biologic Pipeline: A 2012 Assessment of Select Major Companies 187

      Success Rates by Phase of Drug Development: Small Molecule Drugs vs. Biologics 188

      Companies Rank Ordered by Percentage of Phase 2 and Phase 3 Pipeline Drugs That Are Biologies 188

      Companies Rank Ordered by Absolute Number of Phase 2 and Phase 3 Pipeline Drugs that are Biologics 188

Is Pharma Innovation Crisis a Myth? 189

Medical Decisions and In Vitro Diagnostics 189

Multi-Billion Dollar Pharma Deals to Return? 189

Pharma R&D Productivity: A 2012 Assessment 190

      R&D Productivity: Peak Sales of New Drugs vs. Prior R&D Spend 190

      Peak Sales vs. R&D by Company, Launched Cohort of 2012-2016—Probability Adjusted 190

      Drag Launches: Industry Shows a Broad Range of Outcomes 190

      Number of "Blockbusters" Launched 2012 to 2016, Probability Adjusted 191

      Number of "Blockbusters" Launched 2012 to 2016, Not Probability Adjusted 191

      NPV of R&D Versus 7 yr. R&D Including and Excluding Recently Launched Products 191

      Diseconomies of Scale Still Evident in R&D: R&D Productivity vs. Cumulative R&D Investment 192

      R&D Productivity Over Time, 1999-2012 192

      Pivotal Phase 3 Clinical Trial Success: % of Positive Results by Value of Peak Commercial Potential 192

Personalized Medicine: From Companion Diagnostics to Holistic Decision Support 193

      Example Treatment Decision Support Tests 193

      Cumulative Number of U.S. Treatment Decision Support Tests by Purpose and CAGR, 2004-2011 194

      U.S. Personalized Medicine Partnerships, 2009-2011 194

      Example Partnerships Including Holistic Decision Support Elements 195

When Pharma Companies are Beginning Companion Diagnostic Development 196

      Drug Development Phase When Companies Begin Companion Diagnostics Development 196

State of the Molecular Diagnostics Industry: A 2012 Assessment 197

      MDx Market by Geography 197

      MDx Market Growth, 2010-2016 197

      Roche Has One-Third Share in MDx 198

      MDx Market Overview by Test Type 198

      Market Share by Disease 198

      Market Size by Disease, 2010 vs. 2016 198

How the Dearth of Clinically Useful Diagnostics Hinders Growth in Personalized Medicine 199

      Approved Drugs with Biomarkers 199

      Test Evidence Appears to Have Little Impact on Health Outcomes 199

      Lack of Clinical Usefulness of Diagnostics Leads to More Restrictions on Reimbursement 200

The Economic Power of Orphan Drugs: A 2012 Assessment 201

      Growth Rate of Orphan vs. Non-Orphan Drugs, 2001-2010 201

      Top Revenue-Generating Orphan Drugs 201

Section 3: Market Access/Reimbursement/Drug Pricing

Avoiding HTA Drug Failures: The Case for Evidence-based Development Programs 203

      Outcomes of Reimbursement Submissions for Four Major HTA/Reimbursement Agencies, 2012-2014 203

Drug Prices and Placing a Value on Good Health 204

Intensifying Regulatory Agency Interactions with HTA Bodies: A European Medicines Agency (EMA) Perspective 204

Roche's Schwan on Setting Drug Prices 204

Regulatory Approval for Oncologies on the Basis of Phase II Data: What It Could Mean for Reimbursement 205

      Timelines and Outcomes for Relevant EMA Submissions 205

      EMA Approval Requirement 1: No Therapeutic Alternative 205

      Overall Response Rates Stratified by EMA Approval Status 206

      Timelines and Outcomes of Relevant FDA Submissions 206

      Proportion of Submissions Through the FDA Accelerated Approval Process 207

      Comparators for Indications Assessed by the FDA 208

Value-based Assessment and NICE 209

      Additional Effectiveness Information Required Under Value-based Assessment 210

      What is QALY? 212

      What is an ICER? 212

Drug Pricing Controversies: Not Just Regarding New Drugs Any Longer 213

      Average Number of Price Increases per Year for Ten Biotech Products, 1998-2013 213

      Average Magnitude of Annual Price Increases for Ten Biotech Products, 1998-2013 213

Faster Patient Access to Cancer Drugs: U.S. vs. Europe 214

      FDA- and EMA-Approved Oncology New Molecular Entities and Biologics, 2000-2011 214

      Insurance Coverage of Cancer Drugs in the U.S. and Europe 216

      Europe Imposes More Delays on Reimbursement Than Does the U.S 216

      FDA- and EMA-Approved Oncology New Molecular Entities and Biologics, 2000-2011 217

U.K.'s Not-So NICE Treatment of Pharma Innovation 217

      ...And NICE CEO Responds 217

Section 4: Drug Development Costs/Complexity, Development Time, and Success Rates

Costs/Complexity

Indexed Measures of Clinical Trial Costs: Cost per Patient, 2012-2013 219

      Index of Median Cost per Patient in Clinical Trials by Clinical Phase, 2012-2013 219

      Index of Median Cost per Patient in Clinical Trials by Region, 2012-2013 219

      Index of Median Cost per Patient in Clinical Trials by Therapeutic Area, Phase I IV, 2012-2013 219

      Index of Median Cost per Patient in Clinical Trials by Therapeutic Area, 2012-2013, Phase I 219

      Index of Median Cost per Patient in Clinical Trials by Therapeutic Area, 2012-2013, Phase II 220

      Index of Median Cost per Patient in Clinical Trials by Therapeutic Area, 2012-2013, Phase III 220

      Index of Median Cost per Patient in Clinical Trials by Therapeutic Area, 2012-2013, Phase IV 220

Selected AstraZeneca Clinical Trial Metrics, 2013 220

      Patients in Global AstraZeneca Studies by Region, Drugs vs. Biologics 220

      AstraZeneca's Use of Clinical Research Organizations, 2013 220

Indexed Clinical Trial Costs: Costs per Visit in Clinical Trials, 2012-2013 (IMS Health) 221

      Yearly Cost per Visit Inflation by Region, 2010-2011 vs. 2012-2013 221

      Index of Median Cost per Visit in Clinical Trials, by Phase, 2012-2013 221

      Index of Median Phase I-IV Cost per Visit in Clinical Trials, by Therapeutic Area, Global, 2012-2013 221

      Index of Median Phase I Cost per Visit in Clinical Trials by Therapeutic Area (Global), 2012-2013 221

      Index of Median Phase II Cost per Visit in Clinical Trials by Therapeutic Area (Global), 2012-2013 221

      Index of Median Phase III Cost per Visit in Clinical Trials by Therapeutic Area (Global), 2012-2013 221

      Index of Median Phase IV Cost per Visit in Clinical Trials by Therapeutic Area (Global), 2012-2013 222

      Relative per Visit Grant Costs In Selected Western European Countries, 2012-2013 222

      Index of Comparative Median per Visit Grant Costs in Selected Eastern European Countries, 2012-2013 222

      Index of Comparative Median per Visit Grant Costs In Selected Asia Pacific Countries, 2012-2013 222

      Index of Comparative Median per Visit Grant Costs In Selected Latin American Countries, 2012-2013 222

      Percent of Grants that Include a Site Start-up Fee by Region, 2010-2011 vs. 2012-2013 222

      Index of Comparative Median per Visit Grant Costs In Selected Western European Countries, 2012-2013 223

      Index of Comparative Median per Visit Grant Costs In Selected Latin American Countries, 2012-2013 223

      Index of Comparative Median per Visit Grant Costs In Selected Eastern European Countries, 2012-2013 223

      Index of Comparative Median per Visit Grant Costs In Selected Asia Pacific Countries, 2012-2013 223

Clinical Trials Costs Rise 60%, 2009-2013: Cutting Edge Information 223

Measures of Clinical Trial Costs, 2012-2013 224

      Median Outpatient Reimbursement per Visit in Clinical Trials by Phase, Worldwide, 2012-2013 224

      Median Outpatient Reimbursement per Visit in Clinical Trials by Year, Worldwide, 2012-2013 224

      Median Outpatient Reimbursement per Visit in Clinical Trials by Therapeutic Area, Worldwide, 2012-2013 224

      Total Cost of Procedures as Percentage of Cost per Patient by Therapeutic Area, 2012 and 2013 225

      Screen Failure Cost as Percentage of Total Cost per Patient by Therapeutic Area, US, 2011 and 2012 225

      Average Percentage of Cost Savings per Patient in Indications Using Standard of Care, 2011-2013 225

Indexed Clinical Trial Costs: Median Costs per Patient in U.S. Clinical Trials, 2012-2013 (IMS Health) 226

      Index of Median Cost per Patient in Clinical Trials, by Clinical Phase, U.S., 2012-2013 226

      Index of Median Phase I Cost per Patient in Clinical,Trials by Therapeutic Area, U.S., 2012-2013 226

      Index of Median Phase II Cost per Patient in Clinical Trials by Therapeutic Area, U.S., 2012-2013 226

      Index of Median Phase III Cost per Patient in Clinical Trials by Therapeutic Area, U.S., 2012-2013 226

      Index of Median Phase IV Cost per Patient in Clinical Trials by Therapeutic Area, U.S., 2012-2013 226

Measures of Clinical Trial Cost per Visit, U.S., 2012-2013 227

      Selected Median US Site Costs, Percentage Change from 2010-2011 vs. 2012-2013 227

      Index of Median Phase I Cost per Visit in Clinical Trials by Therapeutic Area, US, 2012-2013 227

      Index of Median Phase II Cost per Visit in Clinical Trials by Therapeutic Area, US, 2012-2013 227

      Index of Median Phase III Cost per Visit in Clinical Trials by Therapeutic Area, US, 2012-2013 227

      Index of Median Phase IV Cost per Visit in Clinical Trials by Therapeutic Area, US, 2012-2013 227

Measures of Clinical Trial Complexity, 2011-2013 (IMS Health) 228

      Index of Clinical Trial Complexity by Trial Phase, Worldwide, 2011-2013 228

      Index of Clinical Trial Complexity by Country/Region, Phase I-IV, 2011-2013 228

      Index of Clinical Trial Complexity by Year, Phase I-IV, Worldwide, 2011-2013 228

      Index of Clinical Trial Complexity by Therapeutic Area, Phase I-IV, Worldwide, 2011-2013 228

Selected Metrics on Clinical Trial Spending and Comparative Trial Costs (IMS Health) 229

c3\Global Clinical Grant Spending by Phase, 2008-2013 229

Index of % Increase in Median Cost per Visit in Clinical Trials by Region, 2011 -2013 229

Annual Cost per Patient Increases/Declines in Phase 2 and Phase 3 Clinical Trials, by Region, 2011-2013 229

US Institutional Overhead: Actual versus Officially Reported Overhead, 2012-2013 229

UK Institutional Overhead: Actual versus Officially Reported Overhead, 2012-2013 229

Index of Median Site Fees per Clinical Study by Phase, All Therapeutic Areas (North America vs. Western Europe), 2012-2013 230

NICE CEO Questions Estimate of Costs to Develop a New Drug 230

A 2013 Assessment of R&D Costs per Approved Drug/Biologic, 2002-2012 230

      Costs per approved molecule are unsustainably high 230

What is the Real Drug Development Cost for Very Small Biotech Companies? 231

      Breakdown of Drug Discovery and Development Costs from the 2010 Eli Lilly Study 231

      Drug Discovery and Development Costs from the 2010 Eli Lilly Study: Per Phase and Per Drug Out-of-Pocket Costs 231

Clinical Trial Enrollment Statistics at Roche, 2011-2013 232

      Number of Subjects/Sites in Trials Sponsored by Roche, 2010-2013 232

      Number of Patients in Roche Clinical Trials by Income Level, 2013 232

Cost Rankings for Biotech Company and Clinical Trials Management Firm Across Countries/Cities: A 2014 Analysis 233

      Summary of Operating Parameters for a Biomedical Research Facility 233

      Country-specific Rankings for Costs of Biomedical R&D Operation 233

      City-specific Index and Ranking for Cost: Biomedical R&D Operation 233

      Summary of Operating Parameters for a Clinical Trials Management Firm 234

      Country-specific Rankings for Costs of Clinical Trials Management Firm 234

      City-specific Index and Ranking for Cost: Clinical Trials Management Firm 234

Recent Estimates of the Cost of Developing New Drugs, 2014 235

An R&D Productivity Ranking of the Largest 22 Firms (R&D Spend): A 2014 Analysis 236

      Top 22 Companies (by R&D Spend) Ranked by R&D Performance 236

Another Way to Calculate the Cost of New Drug Development 237

      Company Research Spending per New Drug: 12 Leading Companies 237

Measuring the Return From Pharma Innovation: Is R&D Earning its Investment? 238

      Drivers of Change in IRR, 2010-2013 238

      Change in Cost Allocation, by Phase, 2010 vs. 2011 vs. 2012 vs. 2013 239

      Comparison of Static IRR Results: 2010-2013, by Company 239

      Pipeline Momentum, 2010-2013 240

      Average Outflow and Inflow per Late Stage Pipeline Asset, 2010-2013 241

      Average R&D Cost to Develop a Compound from Discovery to Launch (US$ million) 241

      Source of Late-Stage Pipeline Valuation, 2010-2013 242

      External Component of Late-stage Pipeline Valuations, 2010-13 242

Trial Site Landscape Becomes Less Stable—CenterWatch 242

Measuring R&D Success and Myth: A 2012 Analysis 243

Biomedical Research and Development Price Index, 1990-2019 245

Selected Health Care Inflation Data, 2001-2013 245

R&D Costs by Phase: Recent Leading Estimates 246

Light and Warburton Attempt "A More Realistic" Estimate of Drug Development Costs 247

      ...And Strong Rebuttals from Tufts CSDD and Others 247

The Case for New Drugs and Better Predictive Biomarkers 248

The Case for Orphan Drugs: R&D Costs and Expected Investment Returns 249

      Phase 3 Trial Sizes: Orphan vs. Non-Orphan 249

      Average Phase 3 Trial Sizes 249

      Phase 3 Trials Length (yrs): Orphan vs. Non-orphan 249

      FDA Approval Time: Orphan vs. Non-Orphan 249

      Average Phase 3 and FDA Approval Time: Orphan vs. Non-Orphan 250

      R&D (Phase 3/Filed): NPV 250

The True Cost of Clinical Drug Trials 251

      Estimated Clinical Trial Expenditures for Recent Obesity Drugs 252

      Estimated Clinical Trial Expenditures for GLP-1 Analogues in Diabetes 252

      Estimated Clinical Trial Expenditures for Factor Xa Inhibitors in Cardiovascular Indications 253

      Estimated Clinical Trial Expenditures for Recent Drugs in Selected Rare Diseases 253

      Medicines in Development by Therapeutic Category, 2010 vs. Annual U.S. Deaths, 2009 254

The Mean Number of Countries per Phase III Clinical Trial 255

      Top Ten Trial Locations for Trials Started in 2013 by Therapeutic Area 255

      Average Number of Countries per Trial (Phase III Trials Started in 2013) 255

Global eClinical Solutions Market to Reach $4.8B by 2017 255

Industry-Sponsored Clinical Trials by Region and Phase, 2009-2013 (PAREXEL Consulting) 256

      Worldwide Clinical Trials First Entered in Each Calendar Year, by Country/Region, 2009 2013 256

      Phase I Clinical Trials, as first entered into ClinicalTrials.gov, by Country/Region, 2009-2013 257

      Phase II Clinical Trials, as first entered into ClinicalTrials.gov, by Country/Region, 2009-2013 258

      Phase III Clinical Trials, as first entered into ClinicalTrials.gov, by Country/Region, 2009-2013 259

      Phase IV Clinical Trials, as first entered into ClinicalTrials.gov, by Country/Region, 2009-2013 260

The Global Distribution of Clinical Trials: A December 2012 Assessment 261

      Distribution of Trials Included on CIinicalTrials.gov (August 2012). 261

Emerging Clinical Trial Enrollment Benchmarks: Trial Size Statistics for New Drugs Approved in 2013 262

      Key Clinical Trial Enrollment Statistics for NMEs Approved in 2007-2013 262

      Clinical Trial Enrollments for NMEs Approved in 2013 263

Emerging Clinical Trial Enrollment Benchmarks: Trial Size Statistics for New Drugs Approved in 2012 264

      Key Clinical Trial Enrollment Statistics for NMEs Approved in 2006-2012 264

      Clinical Trial Enrollments for NMEs Approved in 2012 265

Emerging Clinical Trial Enrollment Benchmarks: Trial Size Statistics for New Drugs Approved in 2011 266

      Key Clinical Trial Enrollment Statistics for NMEs Approved in 2005-2011 266

      Clinical Trial Enrollments for Selected NMEs Approved in 2011 266

Clinical Trial Sites and "Hidden" Costs: A 2013 Analysis 267

      Site Operating Profit: Topline and Adjusted for Hidden Costs 267

      Hidden Cost Recovery: Dollars Recovered as a Percentage of Dollars Requested by Sites 267

      Investigative Site Expenses as a Percentage of Study Grant Revenue 267

      Examples of Uncompensated Study Costs 267

Emerging Clinical Trial Recruitment Benchmarking Metrics: The Recruitment Funnel Analysis 268

      The Recruitment Funnel: 2012 Benchmark Data—CPP and PhESi 268

      The "Typical" Funnel—Average Industry Benchmark 268

      Summary Table of Funnel Metrics Summary 269

      A "Typical" Recruitment Funnel Estimate for a 12-Month Enrollment Period 269

      Screen Failure Rates by Therapeutic Area 270

      Screen Failure Ratio by Phase (Type II Diabetes Mellitus) 270

      Understanding Screen Failure Reasons (Breast Cancer Example) 270

      Patient Completion Rate by Disease 270

      Patient Drop-out Characteristics: Type II Diabetes 271

      Patient Drop-out Characteristics: Schizophrenia 271

      Patient Drop-out Characteristics: Crohn's Disease 271

      Patient Drop-out Characteristics: COPD 271

      Observations About Drop-out Ratios and Reasons 271

      An "Optimized" Funnel 272

Does Enrollment in Cancer Trials Improve Survival Rates? 272

Various Enrollment Benchmarks from StudyOptimizer: Clinical Study-Related Performance Metrics (IMS Health) 273

      Median Site Startup vs. Cycle Time by Selected Therapeutic Areas, Phase II-IV, 2010-2012 273

      Median Site Startup vs. Cycle Time, by Selected Therapeutic Areas, Phase II-IV, 2010-2012 273

      Median Site Startup vs. Cycle Time, by Selected Therapeutic Areas, Phase II, 2007-2012 273

      Median Site Startup vs. Cycle Time, by Selected Therapeutic Areas, Phase III, 2007-2012 273

      Median Site Startup vs. Cycle Time, by Selected Countries, Phase II-IV, 2010-2012 274

      Median Site Startup vs. Cycle Time by Phase, 2010-2012 274

      Patients per Study, by Phase II- IV, 2007-2012 274

      Patients per Study by Region, 2007-2012 274

      Relative % of Mean Patients per Study, Phase II & III, by Selected Therapeutic Areas, 2007-2012 274

      Sites per Study, by Selected Therapeutic Areas, 2007-2012 275

      Sites per Study by Phase II-IV, 2007-2012 275

      Sites per Study, by Region, 2007-2012 275

      Median Countries per Study and Sites per Country, by Phase, 2007-2012 275

      Relative % of Countries per Study, Phase II & III, by Selected Therapeutic Areas, 2007-2012 275

      Relative % of Sites per Country, Phase II & III, by Selected Therapeutic Area, 2007-2012 275

      Median Screen Failure %, by Phase, 2007-2012 276

      Relative % of Median Screen Failures, Phase II & III, by Selected Therapeutic Areas, 2007-2012 276

      Relative % of Median Screen Failures, Phase II & III, by Selected Indications, 2007-2012 276

      Weekly Randomization Rale, by Phase, 2007-2012 277

      Relative % of Median Weekly Randomization Rates, Phase II & III, by Selected Indications, 2007-2012 277

      Relative % of Median Weekly Randomization Rates, Phase II & III, by Selected Therapeutic Areas, 2007-2012 277

Social Media Used for Patient Recruitment in 11% of Trials-Tufts CSDD Study 277

The Use of Mobile Health in Clinical Trials: A 2014 Analysis 278

      Patient Reported Use of Mobile Devices in Clinical Trials 278

      Mobile Health Application Development at 20 Sponsors: Internal vs. External 278

Number of Patients Studied Prior to Approval of New Medicines: A Database Analysis 279

      Boxplots with Medians of the Number of Patients Studied before Approval 280

      Number (percent) of Medicines Categorized According to Total Number of Individuals Studied Prior to Marketing 280

      Number (percent) of Medicines Categorized According to Total Number of Individuals Studied for 6 and 12 Months (long term) Prior to Marketing 281

      Study Sample Sizes Required to Detect Adverse Effects of Medicines in Trials and Cohort Studies 282

No Regional Variability in Clinical Trial Data Quality—New Study 282

A New Benchmark Created for Patient Recruitment and Enrollment: A 2013 Analysis 283

      Share of Sites per Region Ready-to-Recruit that Enroll at Least One Patient 283

      Actual Enrollment as Share of Target Enrollment for Sites by Region 283

      Screen and Randomization Rates by Therapeutic Area 283

      Phase II and III Enrollment Performance on a Multi-Center Study 284

      Recruitment Tactic Usage by Region 284

      Nearly One-Third of Studies Do Not Receive Centralized Recruitment Support 284

Do Trial Disclosures Hurt Ongoing Trials? 284

The Impact of "Rejuvenation" Meetings on Enrollment 285

      Impact of Focused Enrollment Optimization Training with Study Team, CRO, CRAs, Gastroenterology Indication 285

      Cumulative Enrollment Progression Pre and Post Rejuvenation Meetings: Nephrology Indication 285

      Impact Graphs: Global Trials for Autoimmune Disease 286

      Study Enrollment Metrics: Oncology Clinical Trial Pre and Post Various Rejuvenation Meetings 286

      Impact Graph: Pediatric Neurology Indication 286

      Overall Impact of DAVA Involvement 286

      Rejuvenation Meeting Impact Growth: Cardiovascular Indication 286

The Challenges of Complex Oncology Trials: A 2012 Analysis 287

      Estimated Time to Enroll FDA-regulated Phase 3 Cancer Studies 287

      Trends in Oncology Trial Protocol Complexity 287

Demographics of Clinical Trial Populations: A Look at NIH Trials, 2012 288

Global Clinical Trial Sites: Various Metrics 289

      Global Investigative Site Staffing 289

      Global Investigative Site Mean Revenue and Profitability 289

      Are Global Trials Really Faster? 289

      Key Performance Metrics for Investigative Sites by Region 289

      Revenue and Profitability by Investigative Site Size 289

      Allocation of Clinical Trial Grant Expenses 289

      Distribution of Investigators by Site Type 289

      The Investigative Site Landscape in Western Europe 290

      Average Clinical Trial Grant Size, 2010 vs. 2011, North America and Europe 290

Risk-based Monitoring's Slow Start 290

      Proportion of Companies Performing 100% Source Verification 290

      Days Spend on Site Each Month by Study Monitors 290

      Average Cycle Time from Pre-Study Visit to Site Initiation 290

Improving Clinical Research Performance and Reducing Costs Through Clinical Protocol Designs 291

      Phase II and III Protocol Demands and Work Burden: 2000-2011 291

      Phase II and Phase III Study Size and Scope: 2011 291

      Distribution of Procedures by Type for Phase II and Phase III Programs 291

      Protocol: Objectives and Endpoints, 2012 292

      Procedure Distribution by Endpoint Type, 2012 292

      Distribution of Total Direct Study Procedure Costs by Type, 2012 292

      Proportion and Direct Cost of Protocol Procedures by Endpoint Type 292

Global Clinical Trial Sites Rate Study Sponsors: A 2013 Analysis 293

      Sponsors Receiving Top Relationship Rates from Their Sites 293

      Site Assessment of Relationship Attribute Importance and of Sponsor Ability to Provide Them 293

      Gaps Between Relationship Attribute Importance and 'Excellence' Ratings of Sponsor Ability to Provide Them 294

      Sites Rate Each Company's Overall Reputation as a Sponsor of Clinical Research 294

Global Site Landscape: A 2013 Assessment 295

      Active Unique Investigators Filing Form 1572s Worldwide 295

      PI Growth by Region: Share of Pis Worldwide, by Region, 1996-2012 295

      Growing Proportion of Community-based Principal Investigators, 2006-2012 295

      Start-up and Enrollment Times: Global Site Performance by Region, 2012 296

      Global Investigator Turnover Rates by Region and Site Type, 2012 296

Topol Urges Moving Beyond the Randomized Trial 296

Where Are Clinical Trials Being Conducted? Follow the Inspections 297

      CDER-DSI International Clinical Investigator BIMO Inspections, FY2012 297

      EMA GCP Inspections Related to the Centralized Procedure: Total GCP Inspections per Country, 2010, 2011, and 2012 297

Comparator/Co-Therapy Drug Costs in Clinical Trials: A 2013 Analysis 298

      Incidence of Comparator Drug Use in Clinical Trials, 2009-2012 298

      Distribution of Comparator Drags by Type 298

      Mean Number of Full-time Staff Dedicated to Obtaining Comparator Drugs/Co-Therapies, 2009-2013 299

Investigator Factors, Ease of Approval Drive EU Trial Site Selection Decisions—New Study 299

Activating Investigative Sites in a Staggered Process: Challenges and Solutions 300

      A Typical Site Activation Curve by Using Staggered Site Activation 300

      First Quartile of Country Activation Cycle Times 301

      Altered Site Activation Curve by Activating All the Sites Spontaneously 301

      Study Start Up Resource Curve in a Staggered Site Activation 302

      Study Start Up Resource Curve in an "All Out" Site Activation 302

Downturn in Cardiovascular Research Concerns Docs 302

How Scientific Advances and New Drug Approvals Raise the Bar for New Clinical Trials and Approvals: An Oncology Case Study 303

      New Drugs Developed with Standard Regimen: Regulatory and Clinical Hurdles are Raised with Each New Approved Regimen 303

      The Statistical Dilemma 303

The Limited Utility of Biomarkers: A 2008 Assessment of Biomarkers in Early Cancer Drug Development 304

      Biomarkers and Surrogate Endpoints are Often Confused 304

      Biomarkers Have Much Appeal in Expediting Cancer Drug Development 304

      However, Biomarkers Don't Offer an Easy Solution 304

Globalization of Clinical Research Expands Capabilities, but Creates New Challenges 305

      Location of Clinical Trials, 2000-2012P 305

      Number of Countries Where Clinical Trials Are Conducted 305

Global Biomarkers Market to US$34 by 2017—GIA 305

The R&D Cost of a New Medicine: A 2012 Assessment 306

      Out-of-Pocket Mean Development Costs 306

      Estimates of the Full Cost of Bringing an NME to Market 307

      Hypothetical Out-of-Pocket Spending Needed for. One Successful Medicine 307

      Capitalized Cost per Successful Medicine 308

      Average Clinical Period Cost per Approved New Drug by Therapeutic Class 308

      Costs for New Drugs by Disorder and Primary Indication 309

FDA Quietly Testing Some Generic Drugs for Equivalence to Brand Medicines 310

Development Time

Analysis of U.S. New Drug Development Process by Average Time to Complete Each Phase of Product Development 311

The Effects of Partnerships on Drug Development Times: A 2014 Assessment 312

      U.S.-Approved New Therapeutic Drugs and Biologics, 2000-2011 312

      Trends in Development Relationships, 2000-2011 312

      Distribution of U.S. Approved New Therapeutic Drugs and Biologics, 2000-2011 313

      Mean Clinical, Approval, and Total Phase Times, 2000-2011 313

      Medians for Phase Times for U.S. Approvals, 2000-2011 313

Ceritinib Runs the 'Three-Minute Mile"—Gains Approval After Phase 1 313

The "Drugs Are Being Approved Too Quickly" Argument Evolves: Point/Counterpoint 314

      Percent of CDER's 2013 NME/NBE Approvals Using Various Accelerated Pathways 314

      Rep. DeLauro Questions FDA on Accelerated Approval 314

      FDA Commissioner Defines "Range of Clinical Evidence" Used in Drug Approvals 314

FDA's Pazdur on the Accelerated Approval Program 315

Development and Approval Times for Oncology vs. Non-Oncology Drugs in the U.S.: A 2012 Analysis 316

      FDA Total Development Time by Phase 316

      EMA vs. FDA Approval Time for 2007-2011 Cohorts 316

      FDA Total Oncology Development Time by Phase and Approval Type, 2002-2011 317

      FDA Special Designation Trends 317

      EMA/FDA Oncology Approval Time, Designated vs. Non-Designated Products, 2007-2011 317

      FDA Total Development Time for NBEs and NCEs: Oncology vs. Non-Oncology, 2002-2011 318

New Drag Cycle Times, Discovery and Development, 1998-00 to 2009-11 318

      Drug Cycle Times from 1998-2000 to 2009-2011 Increasing 318

Study Start-up and Enrollment Times: An Analysis of Global Site Performance in 2012 by Region 318

Biopharmaceutical Product Approvals and Development Times: A 2011 Analysis 319

      Categories of Biotech Product Approvals over Three Decades 319

      Indication Approvals for Biotech Products over Three Decades 319

      Phase Lengths for Biotech Products Approved, 2000-2009 319

      Priority and Standard Reviews for Biotech Products by Year of Approval 320

      Phase Lengths for New Biotech Products and NCEs over Three Decades 320

      New Biotech Products and NCEs Approved 2000-2009 320

Cycle Time Metrics for U.S. Multisite Trials 320

Development Times for CNS Drugs: A 2012 Analysis 321

      Mean Clinical-Plus-Approval Phase Lengths for CNS Drugs 321

      Share of New Drug and Biologics Approvals with FDA Priority Rating 321

Analysis of Study Start-up Times by Region 321

Biotech Development Time and Approval Success Rates in Cancer: A 2010 Study 322

      Attrition Rates for 164 RBI Oncology Compounds That Have Reached a Definitive Clinical Outcome 322

      Utilization of FDA Mechanisms for FDA-Approved Compounds: Oncology vs. All Others 323

      Impact of FDA Mechanisms on Mean Development Times for 27 Oncology Compounds 323

      Mean Clinical Phase and FDA Review Times for RBI Oncology Drugs 323

New Drag Clinical and Approval Times: A 2008 Assessment 324

      Clinical and Approval Times, 1984-2007 324

      Clinical Phases for Priority and Standard NCEs Approved 1984-2007 324

      Clinical Phases for NCEs Approved 1999-2007 by Therapeutic Area 324

      Clinical and Approval Times by Therapeutic Class, 2005-2007 324

Success Rates

R&D Attrition Rates: Commonly Cited and Emerging Benchmarks, 2014 325

New Drag and Biologic R&D Success Rates, 2003-2013 326

      Calculating Overall Success Rates 326

      Success Rates by Phase (lead and secondary indications), 2010 vs. 2011 vs. 2012 vs. 2013 326

      Success Rates by Phase, NME vs. All Drugs, 2013 326

      Phase Success Rates by Molecule Type: Drugs, Biologics, and Non-NMEs 326

      Likelihood of Approval by Phase—NMEs & BLAs, 2010 vs. 2013 327

      Overall Success Rates by Therapeutic Area 327

      Success Rates at Phase 2 and Phase 3 by Therapeutic Area 327

      Overall Success Rates for Oncology vs. Non-Oncology Indications by Molecule Type 327

      Oncology vs. Non-Oncology Success Rates by Phase 328

      Overall Success Rates by Oncology Indication 328

      NME Cumulative Approval Rates After Various FDA Review Cycles 328

      Phase Rates by Company, January 2003 December 2013 328

The Causes of Clinical Trial Failures: An October 2013 Analysis 329

      Number of Failures Where Reasons for Failure Are Known, by Therapeutic Class and Phase, 2000-2009 329

      Phase I Reasons for Failure 329

      Phase II Reasons for Failure 329

      Phase III Reasons for Failure 329

      Reasons for Failure Among Therapeutic Classes with Relatively High Efficacy Failure Shares 330

      Reasons for Failure Among Therapeutic Classes with Relatively Low Efficacy Failure Shares 330

FDA's Pazdur: More Good Drugs Mean More Easy Calls for Agency Today 330

AIDS Pioneer on HIV Cure and Functional Cure 330

Analysis of Reported Reasons for Drug Discontinuations, 2002-2013 331

New Study Looks at Factors Associated with Likelihood of FDA Drug Approval 331

New FDA Study on Reasons Why New Drugs Fail in NDA Review Process 332

GSK Makes Interesting Pit Stop 332

Could Emerging Drug Classes Rescue R&D Productivity? 333

      Early Clinical Phase Success Rates for ADCs and SMIPPIs vs. NMEs Overall 333

Estimates of Drug Success Rates: Unprecedented vs. Precedented Molecules 333

      Drug Success Rates: Unprecedented vs. Precedented Molecules 333

Clinical Success Rates for New Cancer Drugs: A 2013 Analysis 334

      Tumor Types Included in Studies of Cancer Drugs 334

      Phase Transition Probabilities for Cancer Drugs First Entering the Clinical Pipeline: 1993-2004 334

      Phase Transition Probabilities for Cancer Drugs by Period of First Clinical Testing 334

      Phase Transition Probabilities for Cancer Drugs by Molecular Type 335

      Phase Transition Probabilities for Cancer Drugs by Cancer Type 335

Biotech Drug in Partnerships More Likely to Reach Market—Deloitte Recap 335

Is the R&D Pipeline Improving?: A 2012 Analysis of Success Rates Over Time 336

      Number of New Molecular Entities by Stage Required to Attain One Approval: 2003-07 vs. 2005-09 vs. 2007-11 336

      Success Rates by Phase of Drug Development: 2003-07 vs. 2005-09 vs. 2007-11 336

      Percent of Preclinical Drugs Ultimately Approved: 2003-07 vs. 2005-09 vs. 2007-11 337

New Drug Success Rates: A 2012 Assessment 338

      Probability of Success: Various Studies 338

      Trends in Attrition Rates for Drugs Entering Each Development Phase During Years 1990-2004: Preclinical, Phase I, Phase II, Phase III, and Registration 339

      Number of NMEs Required per Phase for One Successful NME, Based on Recent Estimates for Probability of Success 339

The Problem with Phase 3 Failures: Phase 2 Trials? 340

Pipeline Success Rates for Small Molecule Drugs vs Biologics: A 2012 Analysis 341

      Number of New Molecular Entities Required to Attain One Approval, by Stage: Small Molecule Drugs vs Biologics 341

      Success Rates by Phase of Drug Development: Small Molecule Drugs vs. Biologics 342

      Percent of Preclinical Drugs Ultimately Approved: Small Molecule Drugs vs Biologics 342

Phase 3 Success Rates: No Signs Yet of Improvement, 2009-2012E 343

      Pivotal Phase 3 Clinical Trial Success: % of Positive Results by Value of Peak Commercial Potential, 2009-2012E 343

UK Doc: I'd Rather Have HIV than Diabetes 343

Alzheimer's Disease R&D: Significant Setbacks, Small Gains 344

      Unsuccessful Alzheimer's Drugs in Development 344

Trial Design Characteristics Associated with Success/Failure in Oncology 345

      Number of Oncology Trials Reviewed 345

      Success Rates for Oncology vs. Non-Oncology Products 345

      Characteristics of 500 Phase 2 Oncology Trials 345

      Characteristics of Phase 2 Trials That Completed Phase 3 345

Development Success Rates for CNS Drugs: A 2012 Analysis 346

      Phase Transition Probabilities for Self-Originated CNS Drugs by Period of First Clinical Testing 346

      Transition Probabilities for Phase III to NDA/BLA Submission for CNS Drugs by Period of First Clinical Testing 346

      Clinical Approval Success Rates for CNS Drugs by Period of First Clinical Testing 346

      Clinical Approval Success Rates for CNS Drugs by Period of First Clinical Testing—Mixed Vintages 347

New Drugs vs. Repositioned Drugs: An Analysis of Success Rates 347

      Success Rales: New Development Projects vs. Repositioned Drugs 347

Success Rates in the EMA's Centralized Procedure: Small/Medium-Sized Companies 347

      EMA Centralized Proccdure Major Objections in Day 120 List of Questions for SMEs, 2006-2012 347

Can the Pharmaceutical Industry Reduce Attrition Rates? 348

      Success Rates by Therapeutic Area 348

      Success Rates from First-in-Man to Registration 348

      Success Rates by Stage of Development 348

      Reasons for Attrition 349

Section 4: Regulatory/FDA Statistics

INDs

Number of IND Submissions, 1983-2013 351

Breakdown of Drug Divisions' Active IND Review Workload as of Year-End 2013 351

Woodcock: Industry Important to Patients 351

Breakdown of CDER Divisions' Workload by INDs Received in 2013 352

CDER Holds on Commercial IND Submissions, 1991-2013 352

Clinical Holds on Commercial IND Submissions by Division, 2013 352

NDAs

Number of NDAs Pending at the Close of the Calendar Year, 1984-2013 353

Breakdown of Drug Divisions' Pending NDA Review Workload, Year-End 2013 353

Breakdown of Drug Divisions' Workload by NDAs Received in Fiscal Year 2013 353

Breakdown of Divisions' Workload by Pending NDA Supplements, Year-End 2013 354

CDER Refusal-to-File (RTF) Actions by Year, 1995-2013 354

Key Drug Submission and Approval Statistics, 1996-2013 355

Number of NME Approvals and Approval Times, 1985-2013 355

NME and NBE Submissions to CDER, 2004-2013 356

CDER NME and NBE Approvals, 2004-2013 356

A Look at Drug/Biologic Approvals and Approval Times for Emerging and Traditional Sponsors, 2012 356

      CDER NME/NBE Approvals, Emerging Sponsors vs. Non-Emerging Sponsors, 2011 vs. 2012 356

      Mean and Median NME/NBE Review Times for Emerging and Non-emerging Companies, 2011 and 2012 356

NME Review Time Ranges, 2000-2013 357

Priority/Standard NME Review Gap, 1997-2013 (in months) 357

Median Approval Times for All NMEs by Calendar Year, 1987-2013 357

Average NME Review Times in Months by CDER Division, 2007-2013 358

A 2014 Analysis of CDER First-Cycle Approval Rates for NDAs, FY1996-FY2012 359

First-Cycle Review Outcomes for NMEs/NBEs, FY2000-FY2013 Submission Cohorts 359

Number of NDAs and NMEs Approved by Year, 1987-2013 360

NMEs Approved Based on Therapeutic Potential, 1995-2013 360

Percent of All Approved NDAs and NMEs Receiving Priority Review Status, 1995-2013 360

CDER's Priority NME Approvals by Class of Drug, 2002-2013 360

An Analysis of Review Cycles to Approval for New Drugs 361

      Summary Cycle to Approval Statistics for 2008-2013-Approved NMEs 361

      Distribution of Review Cycles to Approval, 2007-2013 361

A Closer Look at the FDA's 50 Fastest Drug Approvals, 1963-2013 362

A Comparison of FDA and EMA New Drug Review Times, 2011 2014 364

      BioMedTracker Average New Drug Review Times: FDA vs. EMA, 2004-2014 364

      Metrics for U.S.-Approved Drugs, 2011-2014 364

      Metrics for EU-Approved Drugs, 2011-2014 365

      Metrics for Drugs Approved in US or EU in 2011-2014 365

U.S. Quicker to Approve New Drugs Than EMA and Health Canada—New Study 365

U.S. New Drug Approvals of 2013: NDA Review Times by Drug 366

2013 FDA New Medicine Approvals: Beyond the Metrics 366

U.S. New Drug Approvals of 2012: NDA Review Times by Drug 367

Cancer Will Be Leading Cause of U.S. Deaths by 2030 367

U.S. New Drug Approvals of 2011: NDA Review Times by Drug 368

U.S. New Drug Approvals of 2010: NDA Review Times by Drug 368

U.S. New Drug Approvals of 2009: NDA Review Times by Drug 369

U.S. New Drug Approvals of 2008: NDA Review Times by Drug 369

U.S. New Drug Approvals of 2007: NDA Review Times by Drug 370

U.S. New Drug Approvals of 2006: NDA Review Times by Drug 370

U.S. New Drug Approvals of 2005: NDA Review Times by Drug 370

U.S. New Drug Approvals of 2004: NDA Review Times by Drug 371

U.S. New Drug Approvals of 2003: NDA Review Times by Drug 372

U.S. New Drug Approvals of 2002: NDA Review Times by Drug 372

U.S. New Drag Approvals of 2001: NDA Review Times by Drug 373

U.S. New Drug Approvals of 2000: NDA Review Times by Drug 374

Postmarketing Study Commitment Trends for New Drugs: An Analysis of NMEs Approved in 2013 375

      Percent of NMEs Approved with Postmarketing Commitments, 2001-2013 375

      Percent of NMEs Approved with REMS, 2009-2013 375

FDA Touts "Global Drug-Review Leadership" with New Drug Approvals 376

      Global New Active Substance Launches by Region, 2001-2013 376

New Breakthrough Therapy Designation Program: A 2014 Analysis 377

      All NMEs/NBEs with Priority, Fast Track, or Accelerated Approval Designation, 1998-2013 377

      Share of NME/NBE Approvals from Expedited Programs and BTDs with Orphan Designation, 1998-2013 377

      First BTDs Awarded by FDA and Announced Publicly by Sponsors 378

Global Drug-Device Combination Market to Reach $115.1 B by 2019—Report 379

An Analysis of the Factors Associated with First-Cycle Approvals: A 2008 Update 380

      Approval Rate vs. Novelty and Indication 380

      First-Cycle Approval Rate by Application Type 380

      Effect of Pre-NDA/BLA Meetings and Timing on Approval Rate for FY2005-FY2007 Cohort 381

      Major Deficiencies Cited in First Action Letter of Multi-Cycle Applications by Category for FY2002-FY2007 Cohort 382

      Single-Cycle Approval Rates by Sponsor Experience 382

      Approval Rate vs. Sponsor Type and Origin 382

Safety-Based Drug Marketing Withdrawals in the United States, 1980-2012 383

NDAs Approved Under CDER's Accelerated Approval Program, 1992-December 2013 384

Median CDER Total Time to Approval for NMEs/NBEs by Fiscal Year Submission Cohort, 2000-2012 385

Orphan Drug Activity Resumes Record Pace, 2013 386

      Orphan Drug Designation and Approval Statistics, 1991-2013 386

      Prevalence of Orphan Drugs in CDER's NME Approvals, 2001-2013 386

      Cumulative Growth of Orphan Drugs, 1984-2012 387

      Mean Orphan Drug Approval Times vs. Approval Times of Other Drugs, 1999-2013 387

Rare Disease Metrics 387

The Growing Burden of Alzheimer's and Other Dementias 387

Company Treats Anemia Through Different Type of High 387

Over-the-Counter Drugs

Rate of Rx-to-OTC Switches per Year, 1951-2013 388

Wireless Health Market to Almost $60B by 2018—Study 388

In Alzheimer's, Problem is Drugs and Not Regulatory Pathways—Temple 388

Generic Drugs

Pending ANDAs Begin to Level at FDA, 2000-2013 389

Annual ANDA and AADA Submission and Approval Statistics, 2002-2013 389

Mean and Median ANDA/AADA Review Times, 1999-2013 389

Biologics

Summary of FDA Actions on Biologics in 2013 390

      Key FDA Review Statistics for 2013 390

      FDA New Biological Product Approvals for 2013 390

Summary of FDA Actions on Biologics in 2012 391

      Key FDA Review Statistics for 2012 391

      FDA New Biological Product Approvals for 2012 391

Summary of FDA Actions on Biologics in 2011 392

      Key FDA Review Statistics for 2011 392

      FDA New Biological Product Approvals for 2011 392

Summary of FDA Actions on Biologics in 2010 393

      Key FDA Review Statistics for 2010 393

      FDA New Biological Product Approvals for 2010 393

Summary of FDA Actions on Biologics in 2009 394

      Key FDA Review Statistics for 2009 394

      FDA New Biological Product Approvals for 2009 394

Summary of FDA Actions on Biologics in 2008 395

      Key FDA Review Statistics for 2008 395

      FDA New Biological Product Approvals for 2008 395

Compliance

CDER Clinical Site Inspection Results, FY1998-FY2013 396

      CDER Clinical Investigator Inspections, FY1992-FY2013 396

      Clinical Investigator Deficiency Categorics, FY2013 396

      Sponsor/Monitor/CRO Inspection Outcomes, FY2013 396

Section 5: International Statistics

European Union

R&D Spending in Europe's Pharmaceutical Industry, 1980-2013 397

      Pharmaceutical R&D Spending Within EFPIA Countries, 1995 2012 397

Mean EMA Review Time for Human Drugs Submitted Under the EC's Centralized Procedure, 2013 398

      Mean EMA Processing Time for Human Medicinal Products, 2001-2013 398

      Mean Processing Times for Key Stages of Centralized Process, 2000-2013 398

Russia Clinical Trial Numbers Decline in 2013 398

EMA New Medicine Approval Metrics, 2013 399

      Number of EMA NAS Approvals, 2010-2013 399

      Number of EMA Orphan Medicine Approvals, 2009-2013 399

And Some Think Pharma Has Manufacturing Compliance Challenges? 399

A Comparison of FDA and EMA New Drug Review Times, 2011-2014 400

      BioMedTracker Average Review Times: FDA vs. EMA, 2004-2014 400

      Metrics for U.S.-Approvcd Drags, 2011-2014 400

      Metrics for EU-Approved Drugs, 2011-2014 400

      Metrics for Drugs Approved in US or EU in 2011-2014 401

FDA Quicker to Approve New Drugs Than EMA and Health Canada—New Study 401

United Kingdom

The MHRA's Clinical Trials Work, 2012/2013 402

MHRA's New Active Substances Assessed and Mean Assessment Times, 1993-2013 402

Success Rates in the EMA's Centralized Procedure: Small/Medium-Sized Companies 402

      EMA Centralized Procedure Major Objections in Day 120 List of Questions for SMEs, 2006 2012 402

Canada Tries to Make Its Clinical Trials Market More Competitive 402

Germany

Pharmaceutical R&D Expenditures by German Drug Industry, 2003-2012 403

Number of New Chemical Entities Approved in Germany, 1990-2012 403

The VFA Assesses the German Pharmaceutical Environment 403

Japan

Pharmaceutical R&D Expenditures in Japan, 1985-2012 (in bill. Yen) 404

Annual Number of New Chemical Entities Approved in Japan, 1984-2012 404

Number of INDs for Investigational New Drags Submitted in Japan, FY2002-2012 404

Success Rates of New Drug Development in Japan, 2008-2012 404

R&D Expenditures of 20 Leading Japanese Pharmaceutical Manufacturers, 2008-2012 405

Number of Prescription Drug Manufacture and Import Approvals Granted in Japan, 1986-2012 405

Median NDA Approval Times in Japan by Year of Submission, 1997-2012 405

Median Development Times for NMEs in Japan, 2000-2012 405

Number of Drags in Development in Japan by Pipeline Stage and Disease/Therapeutic Category, April 2014 406

China

From Imitation to Innovation: A March 2014 Analysis of Biopharma R&D in China 407

      Domestic Chinese Biopharmas: A Pipeline Analysis 407

      IND Submissions to and IND Approvals by CFDA Between 2003 and 1H13 407

      IND Submissions by Therapeutic Class, 2012 vs. 2013 407

      Current Drug R&D Pipeline in China by Therapeutic Class, 2012 vs. 2013 408

      NDA Submissions to CFDA, 2003-2013 408

      NDA Approvals by CFDA, 2004-2013 408

China Poised to Become World's Second-Largest in Biomedical R&D Investment 408

Canada

Canadian Drugs Directorate New Active Substance (NAS) Approval Times, 2000-2012 409

New Drug Submission (NDS) Approval Times in Canada, 2001-2012 409

Korea

The Clinical Trial Market in Korea: A 2013 Analysis 410

      Clinical Trials Approved by KFDA, 1998-2012 410

      KFDA-Approved Multinational Clinical Trials in 2012 by Therapeutic Area and Phase 410

      KFDA-Approved Multinational Clinical Trials in 2012 by Company and Phase 410

      KFDA-Approved Domestic (Local) Clinical Trials in 2012 by Therapeutic Area 410

Global

Trends in Worldwide Pharma and Biotech R&D Expenditures, 2006-2020P 411

      Global R&D Spending by World's Top 500 Pharma & Biotech Companies, 2006-2020P 411

Global New Active Substance Product Launches, 2013. 412

Pfizer and AstraZeneca Join New UK Personalized Cancer Medicine Effort 412

Clinical Trial Activity Trends in Asia: A 2013 Analysis 413

      Investigator Growth in North America vs. Asia, 2010-2012 413

      The Number of Unique Principal Investigators in Southeast Asia 414

      The Number of Unique Principal Investigators in South Asia 414

      The Number of Unique Principal Investigators in East Asia 415

Canadian Researcher Urges Caution in Using Newly Approved Drugs 415

Canada Should Adopt FDA and EMA Drug Approval Decisions—Fraser Institute 415

Global Clinical Trials: A Focus on Latin America and Other Emerging Regions 416

      Number of Clinical Studies Conducted in Key Emerging Market Countries, 2003-2013 416

      Growth in Clinical Trials for Selected Major and Emerging Countries and Regions, 2003 to 2013 416

      Number of Industry-Sponsored Clinical Studies Conducted in Key Emerging Market Countries, 2003-2013 416

Growth in Industry-Sponsored Clinical Trials for Selected Major and Emerging Countries and Regions, 2003 to 2013 416

Comparative R&D Spending and Product Launch Trends Worldwide: A 2014 Analysis 417

      Geographic Distribution of PhRMA Member R&D Spend, 2012 417

      Pharmaceutical R&D Expenditure Annual Growth Rate, US vs. Europe, 1994 2013 417

      Pharmaceutical R&D Expenditure in Europe, the United States, and Japan, 1995-2013 418

      Markets of First Launch for 47 New Active Substances (NAS) Introduced in 2013 418

Faster Patient Access to Cancer Drugs: U.S. vs. Europe 419

      FDA- and EMA-Approved Oncology NMEs and Biologics, 2000-2011 419

      Insurance Coverage of Cancer Drugs in the U.S. and Europe 420

      Europe Imposes More Delays on Reimbursement Than Does the U.S 421

      FDA- and EMA-Approved Oncology NMEs and Biologics: Recommendations for Listing, 2000-2001 421

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