Contents

About the Author xi
Preface xiii
Acknowledgments xv
Abbreviations xvii

SECTION 1 - Introduction and Overview of a Company and the Industry

1 Introduction to Drug Development --- 3
2 Pharmaceutical Industry: Definitions --- 8
3 The Big Picture --- 15
4 Standards: Types, Uses, and Issues --- 34
5 Pharma-think, Academic-think, and
Government-think --- 45
6 Pharma Sense versus Common Sense --- 55

SECTION 2 - Basic Principles, Strategies, and Approaches

7 Overview of Factors Affecting Drug Discovery --- 61
8 The Drug Discovery Process --- 68
9 Golden Rules of Drug Discovery --- 97
10 The Drug Development Process --- 104
11 Golden Rules of Drug Development --- 114
12 Biotechnology --- 119
13 Extrapolating Animal Safety and Efficacy Data to Humans --- 132
14 Evaluating and Interpreting Data --- 143
15 Stimulating Innovation and Increasing Efficiency with the Right Questions, People, Milieu, and Approaches --- 151
16 A New Paradigm of Drug Development --- 167
17 Future Environments for Drug Discovery and Development --- 172

SECTION 3 - Corporate Organization and Management Issues

18 Models of International Operations --- 183
19 Organization at the Corporate Level --- 191
20 Corporate Management --- 202
21 Reducing Pharmaceutical Risk --- 225
22 Enhancing Communication --- 231
23 Personnel and Staffing Issues --- 246
24 Competitive Intelligence --- 261
25 Conflicts of Interest and Bias --- 266
26 Crisis Management --- 280
27 Mergers, Joint Ventures, and Alliances --- 287
28 Pharmacopolitics --- 298
29 Institutional Memory --- 308
30 Differences among Pharmaceutical Companies --- 315

SECTION 4 - External Corporate Relationships and Interactions

31 Interactions and Relationships between Academicians and Industry --- 331
32 Investigator-sponsored Research Proposals Submitted to Industry --- 341
33 Technology Transfer from Academia to Industry --- 345
34 Interactions between Pharmaceutical Companies --- 349
35 Interactions with Trade Associations --- 354
36 Interactions with Legislators and Government Agencies --- 359
37 Interactions and Relationships with Healthcare Professionals --- 370
38 Interactions with Patients and the Public --- 374
39 Patient Package Inserts --- 384
40 Interactions and Relationships with the Media --- 391

SECTION 5 - Research and Development Organization, Management, and Assessments

41 Organizing Research and Development --- 401
42 Managing Research and Development and Avoiding Tangents --- 410
43 Personnel Issues in Drug Discovery and Development --- 429
44 Myths about the Pharmaceutical Industry and Drug Development --- 436
45 Fads and Fashions in Drug Development --- 441
46 The Many Facets of Reality: Approaches to Issues and Problems --- 446
47 International Organization and Management --- 451
48 Project Management: Balancing Line Function and Matrix Approaches --- 460
49 Choosing the Number and Types of Drugs to Develop --- 475
50 Choosing Standards for Developing Drugs --- 480
51 Creating and Using Benchmarks --- 489
52 Evaluating a Portfolio of Investigational Drug Projects 496
53 Compassionate Use Programs --- 529
54 Virtual Drug Development --- 533
55 Developing and Marketing Orphan Drugs for Rare Diseases --- 544
56 Productivity and Project Success --- 553
57 Overview of Safety and Risk Management --- 569
58 Developing Standard Operating Procedures --- 578

SECTION 6 - Clinical Activities and Issues

59 Introduction to Clinical Trials --- 589
60 Creating a Clinical Strategy and Development Plan for a New Drug or Indication --- 603
61 Designing and Implementing a Clinical Trial --- 615
62 Questions to Ask about a Clinical Trial Protocol --- 640
63 Dose-response Relationships in Clinical Trials --- 644
64 Collecting and Interpreting Life Events Data in Clinical Trials --- 655
65 Quality of Life and Pharmacoeconomics in Clinical Trials --- 662
66 Overview of Phase 4 and Postapproval Clinical Activities --- 677
67 Phase 4 Trials and Postapproval Pharmacovigilance Methodologies --- 685
68 Feasibility of Multinational Trials --- 693
69 Groups that Influence Protocol Design --- 707
70 Monitoring and Auditing a Clinical Trial --- 712
71 Electronic Data Collection and E-clinical Trials --- 721
72 Principles of Patient Recruitment and Retention --- 733
73 Surrogate Endpoints and Biomarkers --- 737
74 Contract Research Organizations and Outsourcing Strategies --- 746
75 Conducting Clinical Trials Efficiently and Rapidly --- 756
76 Clinical Significance --- 765
77 Incorporating Benefit-to-risk Determinations in Drug Development --- 771
78 Interactions between Clinicians and Statisticians for Analysis and Interpretation of Clinical Data --- 780
79 The Concept of Normalcy --- 787
80 Recruiting and Training Clinical Investigators --- 797
81 Human Subject Protection and Ethical Issues in Clinical Trials --- 807
82 Improving the Standards of Clinical Trial Publications .819
83 Registries and Directories of Clinical Trials, plus Disclosure of Their Results and Archiving Their Data --- 823
84 Clinical Trials Come of Age --- 832

SECTION 7 - Regulatory Affairs Activities and Issues

85 Introduction to Regulatory Affairs --- 841
86 Negotiating and Interacting with Regulatory Agencies --- 859
87 Learning Which Regulatory Guidances and Standards May Be Modified --- 867
88 Preparing for and Holding Meetings with Regulatory Agencies --- 873
89 Food and Drug Administration Advisory Committee Meetings --- 884
90 Regulatory Applications for Marketing Approval and Global Interactions with Regulators --- 891
91 Regulatory Strategies in Real-life Product Development --- 902

SECTION 8 - Marketing Activities, Issues, and Interactions with Medical Affairs

92 Overview of Marketing Activities and Issues --- 911
93 Corporate Issues Regarding the MedicalÐMarketing Interface --- 946
94 Organizational and Staffing Issues Regarding the MedicalÐMarketing Interface --- 954
95 Marketing Needs, Wants, and Issues in Developing Drugs --- 963
96 Joint Medical and Marketing Activities --- 972
97 Switching Prescription Drugs to Over-the-counter Status --- 986
98 Costs and Pricing --- 993
99 Providing Product Information to Healthcare Professionals --- 1007

SECTION 9 - Functional Activities and Issues

100 Information Management --- 1021
101 Selected Statistical Issues --- 1038
102 Data Management --- 1049
103 Toxicology Activities and Issues --- 1058
104 Animal Testing and Animal Welfare --- 1065
105 Pharmacokinetics --- 1072
106 Licensing Activities and Issues --- 1077
107 Technical Development Activities and Issues --- 1102
108 Production Activities and Issues --- 1119
109 Patent Activities and Issues --- 1144
110 Legal Activities and Issues --- 1159
111 Financial Activities and Issues --- 1172

SECTION 10 - Overview of Current and Future Development

112 Poor Development and Corporate Practices: Threats to a Pharmaceutical Organization --- 1191
113 Keys for Pharmaceutical and Development Success --- 1201
114 Computer Simulations and Modeling --- 1214
115 The Future of Drug Discovery and Development --- 1221

SECTION 11 - Case Studies in Clinical Development, Regulatory Affairs, and the Management of Drug Development

116 Clinical Case Studies --- 1231
117 Regulatory Affairs Case Studies --- 1237
118 Management of Drug Development Case Studies -- 1244

Index 1251