Guide to Drug Development This title has been archived.

Author: Bert Spilker, PhD, MD
Affiliation:
Publisher: Lippincott Williams & Wilkins
Publication Date: 2009
ISBN 10: 0781774241
ISBN 13: 9780781774246
eISBN: 9781469867519
Edition: 1st

Description:

Written by one of the foremost authorities on clinical trials, drug development, and regulatory affairs, Guide to Drug Development is a comprehensive review of the principles and activities involved in developing new drugs, devices, and other medical products. The book covers many topics not discussed in any other textbook and includes timely discussions on electronic clinical trials, registries of clinical trials, data mining, computer simulations and modeling, and changing regulatory standards. Each chapter includes practical tips, lessons, guides, firsthand stories, quotes from experts, and three to six questions for group discussion. The last three chapters present twelve case studies each on clinical trials, regulatory affairs, and management of drug development. Spilker's Guide to Drug Development will be the standard reference text for everyone working on or studying drug discovery or development, in industry, academia, hospitals, government, and independent laboratories.

Table of Contents

Front Matter

  • ABOUT
  • Books by Bert Spilker
  • DEDICATION
  • About the Author
  • Preface
  • Acknowledgments
  • Abbreviations

SECTION 1 Introduction and Overview of a Company and the Industry

    1: Introduction to Drug Development

    • THREE CONCEPTUAL LEVELS FOR VIEWING PHARMACEUTICAL ACTIVITIES
    • FOUR VALUES OF A DRUG: COMMERCIAL, MEDICAL, SCIENTIFIC, AND IMAGE
    • THE ROLE OF COMMON SENSE IN DEVELOPING DRUGS
    • READING THIS BOOK
    • PERSPECTIVES ABOUT TIME
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    2: Pharmaceutical Industry: Definitions

    • HOW IS A NATIONAL PHARMACEUTICAL INDUSTRY DEFINED?
    • INCLUSION OF NONCOMPANY ORGANIZATIONS WITHIN THE DEFINITION AND SCOPE OF THE PHARMACEUTICAL INDUSTRY
    • OVERVIEW OF THE INDUSTRY
    • PERSPECTIVES FROM WHICH TO VIEW THE PHARMACEUTICAL INDUSTRY AND PHARMACEUTICAL COMPANIES
    • QUESTIONS TO DISCUSS

    3: The Big Picture

    • THE CRUCIAL ISSUE FACING PHARMACEUTICAL COMPANIES TODAY
    • FUNCTIONS OF DRUGS
    • OVERALL PERSPECTIVE OF PHARMACEUTICAL COMPANIES
    • SYNOPSIS OF DRUG DISCOVERY AND DEVELOPMENT
    • METAPHORS OF DRUG DISCOVERY AND DEVELOPMENT
    • INTERFACES IN A COMPANY BETWEEN MAJOR FUNCTIONS
    • RESOURCE ALLOCATION
    • MAJOR CHANGES IN THE PHARMACEUTICAL INDUSTRY SINCE 1962
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    4: Standards: Types, Uses, and Issues

    • THE REGULATORY CASCADE
    • STANDARDS: WHAT, WHY, AND HOW?
    • RELATIONSHIPS AMONG DIFFERENT TYPES OF STANDARDS
    • HOW ARE HIGHER STANDARDS ACHIEVED?
    • STANDARDS OF QUALITY
    • TECHNICAL AND PRODUCTION STANDARDS: REGULATORY ISSUES
    • AUDITING ADHERENCE TO STANDARDS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READING

    5: Pharma-think, Academic-think, and Government-think

    • PHARMA SENSE AND PHARMA-THINK
    • ACADEMIC-THINK
    • GOVERNMENT-THINK
    • CONTRASTING AND COMPARING PHARMA-THINK, ACADEMIC-THINK, AND GOVERNMENT-THINK
    • CONCLUSION
    • QUESTIONS TO DISCUSS

    6: Pharma Sense versus Common Sense

    • CONSIDERATIONS OF COMMON SENSE VERSUS PHARMA SENSE
    • EXAMPLES WHERE PHARMA SENSE AND COMMON SENSE DIFFER
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READING

SECTION 2 Basic Principles, Strategies, and Approaches

    7: Overview of Factors Affecting Drug Discovery

    • THE MATRIX APPROACH AS A FRAME OF REFERENCE
    • NATIONAL LEVEL
    • INSTITUTIONAL LEVEL
    • DEPARTMENTAL LEVEL
    • INDIVIDUAL SCIENTIST LEVEL
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READINGS

    8: The Drug Discovery Process

    • SOURCES OF NEW DRUGS
    • CHOOSING THERAPEUTIC AREAS TO RESEARCH
    • METHODS OF DRUG DISCOVERY
    • SELECTED RESEARCH ISSUES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    9: Golden Rules of Drug Discovery

    • CHOOSING THE APPROPRIATE DISEASE AND THERAPEUTIC AREAS TO RESEARCH AND THE METHODS AND STRATEGIES TO USE
    • CREATING A SUITABLE RESEARCH ENVIRONMENT AND APPROPRIATE ATTITUDES
    • REVIEWING RESEARCH ACTIVITIES AND ALLOCATING RESOURCES
    • STIMULATING INNOVATION BOTH WITHIN AND OUTSIDE THE COMPANY
    • ADVANCING COMPOUNDS INTO DEVELOPMENT
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READING

    10: The Drug Development Process

    • APPROACHES TO DRUG DEVELOPMENT
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    11: Golden Rules of Drug Development

    • PRINCIPLES AND GOLDEN RULES AS STARTING POINTS FOR THINKING ABOUT PROBLEMS
    • PLANS, STRATEGIES, AND SYSTEMS
    • STAFF
    • PORTFOLIO
    • VALUES, ATTITUDES, AND BEHAVIOR
    • REGULATORY SUBMISSIONS
    • GOLDEN RULES FOR VENDORS AND CONSULTANTS
    • ADDITIONAL GOLDEN RULES
    • IMPLEMENTING THESE GOLDEN RULES
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READING

    12: Biotechnology

    • TYPES OF BIOTECHNOLOGY COMPANIES
    • METHODOLOGIES USED BY BIOTECHNOLOGY COMPANIES
    • TRENDS IN BIOTECHNOLOGY RESEARCH
    • PATENT ISSUES
    • INTERNATIONAL COMPETITION
    • BIOTECHNOLOGY AND PHARMACEUTICAL COMPANIES
    • SELECTED ISSUES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    13: Extrapolating Animal Safety and Efficacy Data to Humans

    • TYPES AND PURPOSES OF EXTRAPOLATIONS
    • EXTRAPOLATION OF SAFETY DATA
    • PRINCIPLES OF EXTRAPOLATION OF ANIMAL SAFETY DATA TO HUMANS
    • EXTRAPOLATION OF EFFICACY DATA
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    14: Evaluating and Interpreting Data

    • BACKGROUND INFORMATION ABOUT DRUGS AND DISEASES
    • SCIENTIFIC LOGIC AND INTERPRETATIONS
    • FRAMES OF REFERENCE: A TOOL FOR SCIENTISTS AND CLINICIANS TO INTERPRET DATA
    • FORMING A CONCEPT OF A DRUG’S BENEFITS AND RISKS
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    15: Stimulating Innovation and Increasing Efficiency with the Right Questions, People, Milieu, and Approaches

    • ASKING THE RIGHT RESEARCH QUESTION
    • HAVING THE RIGHT PEOPLE AND INTERNAL TEAMS
    • CONSULTANTS
    • CREATING THE RIGHT MILIEU
    • STIMULATING INNOVATION AND CREATIVITY
    • INCREASING EFFICIENCY OF RESEARCH
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    16: A New Paradigm of Drug Development

    • WHY IS A NEW PARADIGM OF DRUG DEVELOPMENT NEEDED?
    • CURRENT PARADIGM OF DRUG DEVELOPMENT
    • NEW PARADIGM OF DRUG DEVELOPMENT
    • IMPLEMENTING THE NEW DRUG DEVELOPMENT PARADIGM
    • KEY POINTS OF THE NEW DEVELOPMENT PARADIGM
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    17: Future Environments for Drug Discovery and Development

    • WILL CHANGE IN THE PHARMACEUTICAL INDUSTRY BE REVOLUTIONARY OR EVOLUTIONARY?
    • INTERNAL COMPANY ENVIRONMENT
    • COMMERCIAL AND BUSINESS ENVIRONMENTS
    • REGULATORY ENVIRONMENT
    • SOCIAL AND POLITICAL ENVIRONMENTS
    • ACADEMIC ENVIRONMENT
    • MEDICAL AND HEALTHCARE ENVIRONMENTS
    • FACTORS UNDERLYING ENVIRONMENTAL CHANGES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL REFERENCES

SECTION 3 Corporate Organization and Management Issues

    18: Models of International Operations

    • TYPES OF SUBSIDIARIES AND DRUG DEVELOPMENT SITES
    • MODELS OF INTERNATIONAL OPERATIONS AND STYLES OF DECISION MAKING
    • MAJOR QUESTIONS AND ISSUES REGARDING THE FIVE MODELS OF INTERNATIONAL OPERATIONS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCE

    19: Organization at the Corporate Level

    • VIEWING AN OVERALL CORPORATE ORGANIZATION
    • MODELS OF A COMPANY’S OVERALL ORGANIZATION
    • CORPORATE ORGANIZATIONAL ISSUES
    • APPROPRIATE SIZE OF A PHARMACEUTICAL COMPANY
    • CRITIQUING THE ORGANIZATIONAL STRUCTURE CHOSEN
    • QUESTIONS TO DISCUSS
    • REFERENCE

    20: Corporate Management

    • COMMUNICATING WITH AND INFLUENCING OTHERS
    • MANAGEMENT MODELS AND STYLES
    • APPROACHES TO MANAGEMENT
    • MANAGING IN AN ENVIRONMENT OF UNCERTAINTY
    • APPROACH TO MAKING MAJOR CHANGES IN A COMPANY
    • DEVELOPING AND IMPLEMENTING MISSIONS, OBJECTIVES, GOALS, AND STRATEGIES
    • ESTABLISHING PRIORITIES
    • JUMPSTARTING A COMPANY WITH CORPORATE MALAISE
    • RECOGNIZING COMPANIES RUN BY PROFESSIONALS VERSUS AMATEURS
    • QUESTIONS TO DISCUSS
    • REFERENCES

    21: Reducing Pharmaceutical Risk

    • MINIMIZING RISK IN SELECTED FUNCTIONAL AREAS
    • SELECTED ISSUES ABOUT MINIMIZING RISK
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READING

    22: Enhancing Communication

    • BARRIERS TO COMMUNICATION
    • TEARING DOWN SILOS AND WALLS
    • METHODS OF COMMUNICATION BETWEEN PROFESSIONALS IN DIFFERENT DISCIPLINES
    • TYPES OF COMMUNICATION PROBLEMS
    • ENHANCING COMMUNICATION
    • QUESTIONS TO DISCUSS
    • REFERENCE

    23: Personnel and Staffing Issues

    • PERSONNEL ISSUES AT THE CORPORATE LEVEL
    • MOTIVATION AND PRODUCTIVITY
    • ATTITUDES OF WORKERS TOWARD DRUG DEVELOPMENT—NEGATIVE, OVERLY OPTIMISTIC, AND REALISTIC
    • LIAISON BETWEEN DIFFERENT FUNCTIONS
    • GOLDEN RULES OF STAFFING
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES

    24: Competitive Intelligence

    • INTRODUCTION, DEFINITIONS, AND PURPOSES
    • SOURCES OF INFORMATION
    • COMPANY SYSTEMS AND ACTIVITIES
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS AND INFORMATION

    25: Conflicts of Interest and Bias

    • DEFINITIONS AND DESCRIPTIONS OF CONFLICT OF INTEREST AND BIAS
    • FACTORS THAT CREATE CONFLICTS OF INTEREST
    • TYPES OF CONFLICTS OF INTEREST INVOLVING PHARMACEUTICAL COMPANIES
    • HOW SHOULD A COMPANY DEAL WITH CONFLICT OF INTEREST?
    • EXAMPLES OF CONFLICT OF INTEREST INVOLVING A PHARMACEUTICAL COMPANY
    • OTHER TYPES OF CONFLICT OF INTEREST FACED BY HEALTHCARE PROFESSIONALS
    • RESPONSES TO CONFLICT OF INTEREST ISSUES BY THE GOVERNMENT AND THE INDUSTRY
    • GOLDEN RULES TO AVOID, PREVENT, OR DEAL WITH CONFLICTS OF INTEREST
    • QUESTIONS TO DISCUSS
    • REFERENCES

    26: Crisis Management

    • THE HIERARCHY OR SPECTRUM FROM QUESTIONS TO CRISES
    • TYPES OF CRISES
    • MANAGING A CRISIS
    • A PROACTIVE APPROACH TO CRISIS MANAGEMENT
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    27: Mergers, Joint Ventures, and Alliances

    • MERGERS AND ACQUISITIONS
    • JOINT VENTURES
    • ALLIANCES BETWEEN COMPANIES AND ACADEMIC INSTITUTIONS
    • CO-MARKETING AND CO-PROMOTION
    • PROCESS FOR CHOOSING PARTNERS FOR COLLABORATION
    • SOCIETAL FORCES AND PRESSURES THAT MAY AFFECT FUTURE MERGERS, ACQUISITIONS, AND ALLIANCES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    28: Pharmacopolitics

    • NARROW VERSUS BROAD DEFINITIONS
    • MAJOR PRESSURES AT THE INDUSTRY LEVEL THAT CREATE PHARMACOPOLITICAL ISSUES
    • MAJOR PRESSURES AT THE COMPANY LEVEL THAT CREATE PHARMACOPOLITICAL ISSUES
    • SELECTED PHARMACOPOLITICAL ISSUES
    • WHY PHARMACOPOLITICAL ISSUES DEVELOP FOR THE PHARMACEUTICAL INDUSTRY AND INDIVIDUAL COMPANIES
    • HOW SHOULD A COMPANY EXAMINE AND ORGANIZE ITS PHARMACOPOLITICAL ACTIVITIES?
    • INFORMING STAFF ABOUT COMPANY POSITIONS
    • INTERACTION AMONG COMPANIES
    • GENERAL STEPS FOR DEALING WITH PHARMACOPOLITICAL ISSUES
    • FUTURE MEGATRENDS THAT WILL AFFECT THE INDUSTRY’S POLITICAL ENVIRONMENT
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READINGS

    29: Institutional Memory

    • COMPONENTS OF INSTITUTIONAL MEMORY
    • WHY IS INSTITUTIONAL MEMORY VALUABLE?
    • HOW IS INSTITUTIONAL MEMORY CREATED AND USED?
    • TYPES OF LESSONS LEARNED IN VARIOUS FUNCTIONS
    • QUESTIONS TO DISCUSS
    • REFERENCE

    30: Differences among Pharmaceutical Companies

    • INSTITUTIONAL CULTURE
    • INSTITUTIONAL MANAGEMENT
    • ATTITUDES AND APPROACHES TOWARD DRUG DISCOVERY AND DEVELOPMENT
    • PHILOSOPHICAL ISSUES THAT VARY BETWEEN COMPANIES
    • QUESTIONS TO DISCUSS
    • REFRERENCES

SECTION 4 External Corporate Relationships and Interactions

    31: Interactions and Relationships between Academicians and Industry

    • TYPES OF INTERACTIONS
    • GUIDELINES FOR INTERACTIONS
    • ALLIANCES BETWEEN COMPANIES AND ACADEMIC INSTITUTIONS
    • LARGE-SCALE RELATIONSHIPS
    • OTHER ISSUES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    32: Investigator-sponsored Research Proposals Submitted to Industry

    • DIFFERING INVESTIGATIONAL NEW DRUG STANDARDS
    • INVESTIGATIONAL NEW DRUG APPLICATION OWNERSHIP
    • HOW PHARMACEUTICAL COMPANIES REVIEW EXTERNAL PROPOSALS FROM ACADEMICIANS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READING

    33: Technology Transfer from Academia to Industry

    • WHAT IS TRANSFERRED?
    • HOW IS IT TRANSFERRED?
    • HOW WELL IS IT TRANSFERRED?
    • HOW DO ACADEMIC SCIENTISTS FEEL ABOUT LICENSING THEIR DISCOVERIES TO PHARMACEUTICAL COMPANIES?
    • WHICH INSTITUTIONS AND COMPANIES ARE ACTIVELY PURSUING LICENSING ARRANGEMENTS?
    • HOW ARE STRATEGIC ALLIANCES BETWEEN ACADEMIC INSTITUTIONS AND PHARMACEUTICAL COMPANIES PERCEIVED?
    • SELECTED PROBLEMS THAT ARISE IN TRANSFERRING DISCOVERIES
    • SELECTED BENEFITS THAT ARISE FROM TRANSFERRING DISCOVERIES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    34: Interactions between Pharmaceutical Companies

    • COMPETITION BETWEEN PHARMACEUTICAL COMPANIES
    • COLLABORATIONS BETWEEN PHARMACEUTICAL COMPANIES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    35: Interactions with Trade Associations

    • ACTIVITIES OF TRADE ASSOCIATIONS
    • MAJOR TRADE ASSOCIATIONS IN THE UNITED STATES
    • MAJOR INTERNATIONAL TRADE ASSOCIATIONS
    • QUESTIONS TO DISCUSS

    36: Interactions with Legislators and Government Agencies

    • PRIMARY GOVERNMENT AGENCIES THAT INTERACT WITH THE PHARMACEUTICAL INDUSTRY
    • LEGISLATURES, LEGISLATION, AND LOBBYING ACTIVITIES
    • INTERACTIONS WITH LEGISLATORS
    • CURRENT AND FUTURE INDUSTRY GOALS
    • CHANGING THE FOCUS OF THE DEBATE
    • CREATING A NEW IMAGE
    • COMPANY ACTIVITIES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    37: Interactions and Relationships with Healthcare Professionals

    • IDENTIFYING HEALTHCARE PROFESSIONALS
    • TYPES OF RELATIONSHIPS
    • SELECTED ISSUES
    • IMPROVING RELATIONSHIPS BETWEEN HEALTHCARE PROFESSIONALS AND PHARMACEUTICAL COMPANIES
    • QUESTIONS TO DISCUSS
    • REFERENCES

    38: Interactions with Patients and the Public

    • DESCRIBING THE PUBLIC
    • THE INDUSTRY’S RELATIONSHIP WITH ITS PUBLICS
    • THE PUBLIC’S RELATIONSHIP WITH THE INDUSTRY
    • EDUCATING THE PUBLIC: FRAMING THE DEBATE AMONG THE PHARMACEUTICAL INDUSTRY, LEGISLATORS, AND THE PUBLIC IN TERMS OF ECONOMIC VALUE
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READINGS

    39: Patient Package Inserts

    • THE RATIONALE FOR PATIENT PACKAGE INSERTS
    • OBJECTIVES OF PROVIDING PATIENT PACKAGE INSERTS
    • MAJOR ISSUES IN PREPARING A MEANINGFUL PATIENT PACKAGE INSERT
    • THE ARGUMENT FOR “CLASS LABELING” OF PATIENT PACKAGE INSERTS
    • POTENTIAL PROBLEMS WITH PATIENT PACKAGE INSERTS
    • RESEARCH ON PATIENT PACKAGE INSERTS
    • ALTERNATIVE SYSTEMS FOR PROVIDING INFORMATION ABOUT DRUGS TO PATIENTS
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    40: Interactions and Relationships with the Media

    • THE INDUSTRY’S RELATIONSHIPS WITH THE MEDIA
    • PUBLIC RELATIONS FOR DRUGS
    • PUBLIC RELATIONS FOR THE PHARMACEUTICAL INDUSTRY
    • QUESTIONS TO DISCUSS
    • REFERENCES

SECTION 5 Research and Development Organization, Management, and Assessments

    41: Organizing Research and Development

    • ORGANIZING RESEARCH AND DEVELOPMENT
    • ORGANIZING RESEARCH AND DEVELOPMENT BY THE MATRIX APPROACH
    • ORGANIZING BASIC SCIENCE DEPARTMENTS
    • ORGANIZING CLINICAL DEPARTMENTS
    • QUESTIONS TO DISCUSS
    • REFERENCES

    42: Managing Research and Development and Avoiding Tangents

    • INTRODUCTION
    • BALANCING WORK EFFORT ON DISCOVERY, DEVELOPMENT, AND LINE-EXTENSION ACTIVITIES
    • ALLOCATING RESOURCES
    • OTHER ISSUES
    • CREATING AND USING CONCEPTUAL MODELS TO KEEP WORK ON DEVELOPMENT PROJECTS FOCUSED
    • MINIMIZING NONPRODUCTIVE TANGENTS
    • MAKING DIFFICULT DECISIONS
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    43: Personnel Issues in Drug Discovery and Development

    • PERSONNEL ISSUES AT THE OVERALL RESEARCH AND DEVELOPMENT LEVEL
    • ABILITY OF PROFESSIONALS TO MOVE IN OR OUT OF THE PHARMACEUTICAL INDUSTRY
    • PERSONNEL ISSUES AT A MEDICAL DEPARTMENT LEVEL
    • QUESTIONS TO DISCUSS

    44: Myths about the Pharmaceutical Industry and Drug Development

    • CONSUMER-BASED MYTHS ABOUT INNOVATION, DRUG DISCOVERY, AND DRUG DEVELOPMENT
    • MYTHS ABOUT INDUSTRY-BASED PRACTICES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    45: Fads and Fashions in Drug Development

    • DIFFERENTIATING BETWEEN CURRENT FASHIONS (I.E., FADS) AND MAJOR INNOVATIONS IN DRUG DEVELOPMENT
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    46: The Many Facets of Reality: Approaches to Issues and Problems

    • THE MANY FACETS OF REALITY
    • PHARMACEUTICAL REALITY
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCE

    47: International Organization and Management

    • MODELS OF INTERNATIONAL COOPERATION AND COORDINATION BETWEEN TWO DRUG DEVELOPMENT SITES WITHIN A MULTINATIONAL COMPANY
    • PLANNING AN INTERNATIONAL CLINICAL PROGRAM
    • IN WHICH COUNTRIES SHOULD CLINICAL TRIALS BE CONDUCTED?
    • DIFFERENT METHODS TO ASSIGN PATIENT QUOTAS AMONG COUNTRIES
    • CREATING PROJECT TEAMS FOR INTERNATIONAL DRUG DEVELOPMENT
    • REVIEWING INTERNATIONAL DEVELOPMENT PROJECTS
    • PITFALLS TO AVOID IN INTERNATIONAL DRUG DEVELOPMENT
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READING

    48: Project Management: Balancing Line Function and Matrix Approaches

    • DEFINITIONS AND BACKGROUND
    • KEY PLAYERS IN A MATRIX SYSTEM
    • INITIATING NEW PROJECTS
    • ESTABLISHING A STRONG VERSUS WEAK MATRIX
    • LONG-RANGE COMPANY PLANNING
    • GOLDEN RULES OF PROJECT MANAGEMENT
    • AUDITING RESEARCH, DEVELOPMENT, AND MANUFACTURING ACTIVITIES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    49: Choosing the Number and Types of Drugs to Develop

    • IDENTIFYING TYPES AND NUMBERS OF PROJECTS TO DEVELOP
    • APPROACHES TO DETERMINING THE NUMBER OF DRUGS TO DEVELOP SIMULTANEOUSLY
    • TO TRIM OR TO ADD—IS THAT THE QUESTION?
    • SPECIAL CASES
    • ANSWERING THE QUESTION OF HOW MANY DRUGS TO DEVELOP
    • QUESTIONS TO DISCUSS
    • REFERENCES

    50: Choosing Standards for Developing Drugs

    • THE NEED FOR STANDARDS TO EVALUATE DRUG DISCOVERY AND DEVELOPMENT
    • RELATIONSHIP OF THE TERMS STANDARDS AND CHARACTERISTICS
    • IDEAL STANDARDS
    • REALISTIC STANDARDS
    • MINIMALLY ACCEPTABLE STANDARDS: THE BEST STANDARDS TO USE
    • “DESIRABLE” VERSUS “ESSENTIAL” CHARACTERISTICS
    • WHO ESTABLISHES THE SPECIFIC SCIENTIFIC AND MEDICAL CHARACTERISTICS FOR THE STANDARDS?
    • ESTABLISHING QUANTITATIVE (OR SEMIQUANTITATIVE) STANDARDS DURING DEVELOPMENT
    • EXAMPLES OF THE THREE TYPES OF STANDARDS
    • OTHER USES FOR MINIMALLY ACCEPTABLE STANDARDS
    • CAN A COMPANY MIX DIFFERENT TYPES OF STANDARDS?
    • CONCLUSION
    • QUESTIONS TO DISCUSS

    51: Creating and Using Benchmarks

    • WHAT ARE BENCHMARKS?
    • EXAMPLES OF PHARMACEUTICAL INDUSTRY BENCHMARKS
    • APPLICATION OF BENCHMARKS
    • CREATING AND USING INTERNAL COMPANY BENCHMARKS
    • PROS AND CONS OF USING EXTERNAL COMPANY (I.E., INDUSTRY) BENCHMARKS
    • GOLDEN RULES OF BENCHMARKS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    52: Evaluating a Portfolio of Investigational Drug Projects

    • OBJECTIVES AND PERSPECTIVES OF A PORTFOLIO ANALYSIS
    • DEVELOPING A PORTFOLIO
    • ANALYZING THE VALUE OF A PORTFOLIO
    • ANALYZING A PROJECT PORTFOLIO IN FIVE STEPS
    • OTHER PORTFOLIO ISSUES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READING

    53: Compassionate Use Programs

    • TYPES OF EXPANDED OR EARLY ACCESS PROGRAMS
    • COMPANY PHILOSOPHIES RELATING TO COMPASSIONATE USE PROTOCOLS
    • ISSUES OF A COMPASSIONATE USE PROGRAM
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    54: Virtual Drug Development

    • DEFINITIONS AND PRINCIPLES OF A VIRTUAL ORGANIZATION
    • ORGANIZATIONAL STRUCTURE OF A VIRTUAL PHARMACEUTICAL DEVELOPMENT COMPANY
    • BUILDING A VIRTUAL COMPANY: A PHARMACEUTICAL EXPERIMENT
    • SPECTRUM OF VIRTUAL COMPANIES
    • LICENSING ISSUES
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READING

    55: Developing and Marketing Orphan Drugs for Rare Diseases

    • PRINCIPLES
    • CLASSIFICATION OF ORPHAN DRUGS
    • THE ECONOMIC–MEDICAL INTERFACE
    • INTERESTED PARTIES
    • SOURCES OF INFORMATION ON ORPHAN DRUGS
    • DISCOVERY, DEVELOPMENT, AND MARKETING OF ORPHAN DRUGS
    • MARKETING BENEFITS IN SELLING ORPHAN DRUGS
    • BENEFITS OF ORPHAN DRUGS FROM A DEVELOPMENT PERSPECTIVE
    • UNITED STATES ORPHAN DRUG ACT OF 1983
    • ESTABLISHING PREVALENCE OR INCIDENCE OF A DISEASE
    • ESTABLISHING DIFFERENCES AMONG DRUGS
    • RATING THE EFFECTS OF THE ORPHAN DRUG ACT IN THE UNITED STATES
    • ORPHAN DRUG ACTIVITES AND LEGISLATION IN EUROPE
    • ORPHAN DRUG ACTIVITES THROUGHOUT THE REST OF THE WORLD
    • WHAT HAS BEEN LEARNED?
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    56: Productivity and Project Success

    • DEFINITION AND DESCRIPTION OF PRODUCTIVITY AND INNOVATION
    • GENERAL METHODS TO MEASURE PRODUCTIVITY
    • SPECIFIC PARAMETERS TO MEASURE PRODUCTIVITY
    • PARAMETERS TO AVOID IN MEASURING PRODUCTIVITY
    • WHAT COMPARISON DATA ARE AVAILABLE?
    • IMPROVING PRODUCTIVITY
    • MEASURING THE SUCCESS RATE OF A COMPANY’S PROJECTS
    • QUESTIONS TO DISCUSS
    • REFERENCES

    57: Overview of Safety and Risk Management

    • DEFINITIONS AND USES OF THE TERMS SAFETY AND RISKS
    • THREE FRAMES OF REFERENCE TO VIEW SAFETY ISSUES
    • MEDICAL AND MEDICATION ERRORS
    • RISK MANAGEMENT PROCESS
    • IMPROVING THE PUBLIC’S UNDERSTANDING OF THE BENEFIT-TO-RISK CONCEPT
    • DILEMMA OF PROTECTING THE PUBLIC VERSUS ALLOWING ACCESS TO DRUGS WHEN THEIR SAFETY PROFILE IS INCOMPLETE
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    58: Developing Standard Operating Procedures

    • DEVELOPING STANDARD OPERATING PROCEDURES
    • CREATING STANDARD OPERATING PROCEDURES THAT ARE A BALANCE BETWEEN BEING REASONABLE AND ONEROUS
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

SECTION 6 Clinical Activities and Issues

    59: Introduction to Clinical Trials

    • PRINCIPLES AND APPROACHES OF CLINICAL TRIALS
    • DRUG SAFETY
    • INTERNAL MEETINGS THAT ENHANCE EFFICIENCY AND EXPEDITE DEVELOPMENT
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    60: Creating a Clinical Strategy and Development Plan for a New Drug or Indication

    • HOW A CLINICAL STRATEGY AND DEVELOPMENT PLAN ARE INFLUENCED BY THE QUESTION POSED
    • CREATING A CINICAL DEVELOPMENT STRATEGY
    • VISUALIZING THE DEVELOPMENT STRATEGY
    • PLANNING THE OVERALL CLINICAL DEVELOPMENT PROGRAM
    • REVIEW OF THE STRATEGY, DEVELOPMENT PLAN, AND STATUS
    • WHEN SHOULD MECHANISM OF ACTION AND OTHER “NICE TO KNOW” STUDIES BE CONDUCTED?
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    61: Designing and Implementing a Clinical Trial

    • OVERVIEW OF STEPS INVOLVED IN A SINGLE CLINICAL TRIAL
    • DESIGNING A CLINICAL TRIAL PROTOCOL
    • ASSESSING SAFETY IN A CLINICAL TRIAL
    • ASSESSING EFFICACY IN A CLINICAL TRIAL
    • HOW TO DECREASE THE MAGNITUDE OF THE PLACEBO RESPONSE IN A CLINICAL TRIAL
    • REVIEWING THE PROTOCOL
    • IMPROVING A CLINICAL TRIAL PROTOCOL AND THE PROCESS OF PREPARING PROTOCOLS
    • USING TEMPLATES, FORMS, AND BOILERPLATE TO SPEED PROTOCOL DEVELOPMENT
    • REQUIRED AND OPTIONAL DOCUMENTS FOR A CLINICAL TRIAL
    • CREATING AN OPERATIONS MANUAL TO ASSIST CLINICAL TRIAL CONDUCT
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    62: Questions to Ask about a Clinical Trial Protocol

    • CATEGORIES OF QUESTIONS
    • QUESTIONS TO ASK AFTER A TRIAL IS COMPLETED
    • QUESTIONS TO DISCUSS

    63: Dose-response Relationships in Clinical Trials

    • INTRODUCTION
    • TYPES OF DOSE-RESPONSE TRIALS
    • ESTABLISHING DOSE-RESPONSE RELATIONSHIPS IN CLINICAL TRIALS
    • SELECTED ISSUES IN DOSE-RESPONSE RELATIONSHIPS
    • PRACTICAL ISSUES IN OBTAINING DOSE-RESPONSE RELATIONSHIPS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    64: Collecting and Interpreting Life Events Data in Clinical Trials

    • BACKGROUND
    • COLLECTING LIFE EVENTS DATA
    • ANALYZING AND INTERPRETING LIFE EVENTS DATA
    • CONCLUSION
    • QUESTIONS TO DISCUSS

    65: Quality of Life and Pharmacoeconomics in Clinical Trials

    • DEFINITION OF QUALITY OF LIFE
    • TYPES OF QUALITY OF LIFE
    • DOMAINS OF QUALITY OF LIFE
    • DIFFERENT PERSPECTIVES ON HEALTH-RELATED QUALITY OF LIFE
    • USES OF QUALITY-OF-LIFE DATA
    • QUALITY OF LIFE FOR INDIVIDUAL PATIENTS AND GROUPS OF PATIENTS
    • SELECTED ISSUES OF QUALITY-OF-LIFE ASSESSMENTS
    • COMBINING QUALITY-OF-LIFE DATA FROM MULTIPLE DOMAINS OR TESTS
    • RELATIONSHIP OF CLINICAL SAFETY AND EFFICACY TO QUALITY OF LIFE: THE FILTERING PHENOMENON
    • INSTRUMENTS USED TO MEASURE QUALITY OF LIFE
    • PHARMACOECONOMICS
    • HEALTH POLICY RELATING TO COSTS OF TREATMENTS
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    66: Overview of Phase 4 and Postapproval Clinical Activities

    • INTRODUCTION
    • SELECTED STRATEGIC AND PROCESS ISSUES
    • REGULATORY ISSUES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    67: Phase 4 Trials and Postapproval Pharmacovigilance Methodologies

    • INTRODUCTION TO POSTAPPROVAL METHODOLOGIES
    • MARKETING TRIALS
    • SPECTRUM OF PHASE 4 TRIALS
    • PASSIVE SURVEILLANCE
    • ACTIVE SURVEILLANCE
    • CLINICAL TRIALS CONDUCTED IN PHASE 4 AT THE ACTIVE END OF THE SPECTRUM
    • BEST INDUSTRY PRACTICES IN THE POSTAPPROVAL PERIOD
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    68: Feasibility of Multinational Trials

    • CONDUCTING A FEASIBILITY EVALUATION FOR A COMPLEX OR LARGE MULTINATIONAL CLINICAL TRIAL
    • DIAGNOSTIC CRITERIA AND CLASSIFICATION SYSTEMS
    • CLINICAL RESEARCH AND INTERNATIONAL TRIALS
    • DIFFERENCES IN MEDICAL PRACTICE AMONG PHYSICIANS IN DIFFERENT COUNTRIES
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    69: Groups that Influence Protocol Design

    • INTERNAL COMPANY INFLUENCES ON AUTHORS OF PROTOCOLS
    • EXTERNAL INFLUENCES ON PROTOCOL DESIGN
    • HOW HAVE THESE INFLUENCES CHANGED OVER TIME?
    • SELECTED ISSUES ABOUT INFLUENCES ON A PROTOCOL
    • QUESTIONS TO DISCUSS
    • REFERENCE

    70: Monitoring and Auditing a Clinical Trial

    • MONITORING
    • AUDITING
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    71: Electronic Data Collection and E-clinical Trials

    • DEFINITION OF AN E-CLINICAL TRIAL
    • BENEFITS AND BARRIERS OF ELECTRONIC DATA COLLECTION
    • MODULAR APPLICATION OF E-BASED CLINICAL TRIALS
    • DIRECT DATA ENTRY INTO COMPUTERS
    • COMPARISON OF ELECTRONIC AND PAPER METHODOLOGIES
    • INTERNET-BASED CLINICAL TRIALS
    • CLINICAL DATA INTERCHANGE STANDARDS CONSORTIUM STANDARDS (CDISC)
    • BACKING-UP AND ARCHIVING E-DATA
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    72: Principles of Patient Recruitment and Retention

    • PATIENT RECRUITMENT PRINCIPLES
    • PATIENT RETENTION PROGRAMS AND STRATEGIES
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    73: Surrogate Endpoints and Biomarkers

    • DEFINITIONS OF CLINICAL ENDPOINTS, BIOMARKERS, AND SURROGATE ENDPOINTS
    • CLASSIFYING BIOMARKERS AND SURROGATE ENDPOINTS
    • TYPES OF SURROGATE ENDPOINTS
    • PHARMACEUTICAL INDUSTRY’S PERSPECTIVE ON SURROGATE ENDPOINTS
    • EXAMPLES OF VALIDATED SURROGATE ENDPOINTS
    • REGULATORY AGENCY AND GOVERNMENT RESEARCH PERSPECTIVES
    • VALIDATION OF SURROGATE ENDPOINTS
    • USES OF BIOMARKERS
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    74: Contract Research Organizations and Outsourcing Strategies

    • OUTSOURCING STRATEGIES
    • TYPES OF CONTRACT RESEARCH ORGANIZATIONS AND THE SERVICES THEY OFFER
    • TYPES OF SITE MAINTENANCE ORGANIZATIONS AND THE SERVICES THEY OFFER
    • MANAGED SITE NETWORKS AND OTHER MODELS
    • SPONSORS’ PERSPECTIVE ON INTERACTIONS AND ISSUES WITH CONTRACT RESEARCH ORGANIZATIONS
    • ISSUES FROM A CONTRACT RESEARCH ORGANIZATION’S PERSPECTIVE
    • ISSUES FROM THE INVESTIGATOR’S PERSPECTIVE
    • SPONSOR’S REGULATORY RESPONSIBILITIES
    • RECENT CHANGES AND DIRECTIONS IN THE CONTRACT RESEARCH ORGANIZATION INDUSTRY
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    75: Conducting Clinical Trials Efficiently and Rapidly

    • WHY ARE EFFICIENCY AND OPTIMAL SPEED OF CLINICAL DEVELOPMENT OFTEN NOT ACHIEVED?
    • OVERALL CLINICAL PLANNING
    • IMPROVING EFFICIENCY AND SPEED IN AN OVERALL PROGRAM
    • SPECIFIC APPROACHES TO IMPROVING EFFICIENCY AND SPEED FOR A SINGLE CLINICAL TRIAL
    • BALANCING QUALITY VERSUS QUANTITY OF DATA TO COLLECT
    • TECHNIQUES TO SPEED DEVELOPMENT PROGRAMS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    76: Clinical Significance

    • THE CONCEPT OF CLINICAL SIGNIFICANCE
    • USES OF THE CLINICAL SIGNIFICANCE CONCEPT
    • COMPARISONS OF CLINICAL AND STATISTICAL SIGNIFICANCE
    • QUESTIONS TO DISCUSS
    • REFERENCE

    77: Incorporating Benefit-to-risk Determinations in Drug Development

    • DEFINITIONS AND PERSPECTIVES
    • ISSUES AND QUESTIONS
    • BENEFIT-TO-RISK CONSIDERATIONS DURING DRUG DISCOVERY, DEVELOPMENT, AND MARKETING
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    78: Interactions between Clinicians and Statisticians for Analysis and Interpretation of Clinical Data

    • BACKGROUND
    • ROLES AND RESPONSIBILITIES FOR DATA ANALYSIS AND DATA INTERPRETATION
    • PARTNERSHIPS BETWEEN A CLINICIAN AND STATISTICIAN
    • STATISTICAL INPUT INTO OTHER AREAS OF RESEARCH AND DEVELOPMENT
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    79: The Concept of Normalcy

    • DEFINITIONS AND DESCRIPTIONS
    • USING THE CONCEPT OF NORMALCY IN CLINICAL TRIALS
    • CHANGING STATES OF NORMALCY
    • QUALITY OF LIFE
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES

    80: Recruiting and Training Clinical Investigators

    • DISCUSSING THE INTEREST OF ACADEMICIANS AND PRIVATE PRACTICE PHYSICIANS IN PARTICIPATING IN PHARMACEUTICAL INDUSTRY RESEARCH
    • TRAINING CLINICAL INVESTIGATORS IN PHARMACEUTICAL RESEARCH AND GOOD CLINICAL PRACTICES
    • EVALUATING THE PERFORMANCE OF CLINICAL INVESTIGATORS
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READINGS

    81: Human Subject Protection and Ethical Issues in Clinical Trials

    • ETHICAL REQUIREMENTS AND GUIDELINES
    • INFORMED CONSENT
    • INSTITUTIONAL REVIEW BOARD/ETHICS COMMITTEE REVIEW OF PROTOCOLS, INVESTIGATORS’ BROCHURES, AND INFORMED CONSENTS
    • GROUPS THAT PROVIDE ETHICAL REVIEW OF PROTOCOLS AND ETHICAL OVERSIGHT BEFORE, DURING, AND AFTER A CLINICAL TRIAL
    • DATA SAFETY MONITORING BOARDS
    • TRIAL DESIGN ISSUES WHEN THE USE OF PLACEBOS IS UNETHICAL
    • DISCLOSING FINANCIAL CONNECTIONS WITH A COMPANY WHOSE PRODUCT IS BEING RESEARCHED OR DISCUSSED
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    82: Improving the Standards of Clinical Trial Publications

    • INCREASING THE STANDARDS OF CLINICAL JOURNAL ARTICLES
    • RIGHTS OF INVESTIGATORS TO PUBLISH THEIR CONTRIBUTIONS TO A MULTICENTER TRIAL SEPARATELY FROM THE OVERALL PUBLICATION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    83: Registries and Directories of Clinical Trials, plus Disclosure of Their Results and Archiving Their Data

    • TYPES OF REGISTRIES
    • COMPANY WAREHOUSES OF CLINICAL TRIAL DATA
    • CLINICAL TRIAL DIRECTORIES FOR VARIOUS STAKEHOLDERS
    • DISCLOSURE OF CLINICAL TRIAL RESULTS TO PROFESSIONALS AND THE PUBLIC
    • CLINICAL TRIAL REPOSITORIES OF RESULTS AND DATA AVAILABLE TO PROFESSIONAL RESEARCHERS AND POSSIBLY TO THE PUBLIC
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    84: Clinical Trials Come of Age

    • CRITERIA TO DEFINE A DISCIPLINE’S COMING OF AGE
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

SECTION 7 Regulatory Affairs Activites and Issues

    85: Introduction to Regulatory Affairs

    • FUNCTIONS OF A REGULATORY AFFAIRS GROUP
    • MAJOR ORGANIZATIONAL LEVELS AT WHICH REGULATORY AFFAIRS PROFESSIONALS OPERATE
    • A SPONSOR’S ORIENTATION TO REGULATORY AUTHORITIES
    • ORGANIZING A REGULATORY AFFAIRS DEPARTMENT OR GROUP
    • COMMENTS ON SELECTED REGULATORY TERMS AND CONCEPTS
    • SELECTED REGULATORY ISSUES
    • INCREASING THE SPEED OF REGULATORY APPROVAL
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    86: Negotiating and Interacting with Regulatory Agencies

    • BACKGROUND OF REGULATORY NEGOTIATING
    • PREPARING TO NEGOTIATE WITH REGULATORY AUTHORITIES
    • CAN ONE NEGOTIATE WITH A REGULATORY AUTHORITY WHEN THEY DETERMINE A FIXED POSITION PRIOR TO MEETING WITH THE SPONSOR?
    • PREPARING TO INTERACT WITH REGULATORS
    • RESOLVING DIFFICULT SITUATIONS AND APPEALING REGULATORY DECISIONS
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    87: Learning Which Regulatory Guidances and Standards May Be Modified

    • INTRODUCTION AND DEFINITIONAL ISSUES
    • REGULATORY STANDARDS THAT MAY BE QUESTIONED OR MODIFIED
    • HOW TO LEARN ABOUT REGULATORY FLEXIBILITY
    • HOW TO KNOW IF THE SHORTCUT CAN BE USED?
    • SPECIFIC EXAMPLES OF NONTRADITIONAL REGULATORY PATHS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    88: Preparing for and Holding Meetings with Regulatory Agencies

    • PRIOR TO THE MEETING
    • PREPARING DOCUMENTS IN ADVANCE OF A MEETING
    • BRIEFING BOOKS SUBMITTED TO A REGULATORY AGENCY IN ADVANCE OF A MEETING
    • REHEARSALS FOR REGULATORY MEETINGS
    • AT THE MEETING
    • AFTER THE MEETING
    • BEHAVIOR BEFORE, DURING, AND AFTER REGULATORY MEETINGS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    89: Food and Drug Administration Advisory Committee Meetings

    • DESCRIPTION OF THE MEETING AND ITS ORGANIZATION
    • BENEFITS AND DISADVANTAGES OF A FOOD AND DRUG ADMINISTRATION ADVISORY COMMITTEE MEETING
    • FOOD AND DRUG ADMINISTRATION ADVISORY COMMITTEE MEETING BRIEFING BOOK
    • PREPARING FOR THE MEETING
    • AT THE MEETING
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    90: Regulatory Applications for Marketing Approval and Global Interactions with Regulators

    • PREPARING A REGULATORY SUBMISSION FOR MARKETING APPROVAL
    • COORDINATION OF RESPONSES TO REGULATORY AGENCIES IN DIFFERENT COUNTRIES ABOUT QUESTIONS ON NEW DRUGS
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READINGS

    91: Regulatory Strategies in Real-life Product Development

    • HOW DOES A COMPANY REFER TO EACH PRODUCT IT IS DEVELOPING?
    • LEAN REGULATORY SUBMISSIONS ARE BETTER THAN FAT ONES: BUT NOT TOO LEAN
    • TYPES AND USES OF META-ANALYSES
    • WHEN CAN A SURVEY BE MORE THAN A COLLECTION OF DATA?
    • IS IT WORTH STRATEGICALLY INCREASING DEVELOPMENT STANDARDS ABOVE THOSE REQUIRED BY REGULATORY AGENCIES?
    • REGULATORY SHORTCUTS CAN BE A DOUBLE-EDGED SWORD
    • QUESTIONS TO DISCUSS
    • REFERENCE

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

    92: Overview of Marketing Activities and Issues

    • INTRODUCTION
    • MARKET CYCLE—BIRTH, LIFE, AND DEATH OF A DRUG
    • IDENTIFYING THE NEED FOR A NEW DRUG
    • ROLES OF MARKETING IN DRUG DEVELOPMENT
    • PROVIDING MARKETING INPUT TO RESEARCH AND DEVELOPMENT DURING DRUG DEVELOPMENT
    • CONDUCTING MARKETING RESEARCH
    • DETERMINING A MARKETING STRATEGY
    • PROVIDING INFORMATION TO CONSUMERS
    • DECIDING WHERE TO SELL A DRUG
    • POSITIONING A DRUG
    • NAMING A DRUG
    • PRICING, COSTS, AND ECONOMICS
    • INTRODUCING A DRUG
    • PROMOTING A DRUG
    • DISTRIBUTING AND SELLING A DRUG
    • PROTECTING A DRUG’S FRANCHISE
    • EXPANDING A DRUG’S MARKET
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    93: Corporate Issues Regarding the Medical–Marketing Interface

    • INTRODUCTION TO MEDICAL–MARKETING INTERACTIONS
    • CORPORATE PERSONALITY
    • ARE THE DECISIONS OF MARKETING OR RESEARCH AND DEVELOPMENT DRIVING THE COMPANY?
    • SELECTED MEDICAL–MARKETING ISSUES
    • QUESTIONS TO DISCUSS
    • REFERENCE

    94: Organizational and Staffing Issues Regarding the Medical–Marketing Interface

    • HOW ARE MARKETING GROUPS ORGANIZED?
    • HOW ARE MEDICAL GROUPS ORGANIZED?
    • WHERE SHOULD VARIOUS GROUPS AND FUNCTIONS BE PLACED WITHIN THE COMPANY’S ORGANIZATION?
    • STAFFING ISSUES
    • ORGANIZATIONAL LINKS BETWEEN MEDICAL AND MARKETING GROUPS
    • QUESTIONS TO DISCUSS

    95: Marketing Needs, Wants, and Issues in Developing Drugs

    • DEFINING MARKETING (AND CUSTOMER) NEEDS AND WANTS
    • COMPARING MARKETING’S NEEDS AND WANTS WITH THOSE OF MEDICAL
    • COMPARING MARKETING PRIORITIES AND RESOURCES WITH THOSE OF MEDICAL
    • MARKETING INFORMATION THAT IS IMPORTANT FOR SCIENTIFIC AND MEDICAL DECISIONS
    • ISSUES THAT CAN LEAD TO PROBLEMS BETWEEN MEDICAL AND MARKETING GROUPS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • ADDITIONAL READING

    96: Joint Medical and Marketing Activities

    • INTERACTIONS BETWEEN MARKETING AND MEDICAL GROUPS
    • COLLABORATIVE APPROACHES TO VARIOUS ACTIVITIES
    • REVIEW OF MARKETING INFORMATION BY MEDICAL STAFF AND VICE VERSA
    • VISUALLY CHARACTERIZING A MARKET
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READING

    97: Switching Prescription Drugs to Over-the-counter Status

    • DEFINITIONAL ISSUES
    • REASONS FOR A COMPANY TO CONSIDER SWITCHING A DRUG TO OVER-THE-COUNTER STATUS
    • MAJOR ISSUES TO CONSIDER BEFORE DECIDING ON A SWITCH FROM PRESCRIPTION TO OVER-THE-COUNTER STATUS
    • STRATEGIC ISSUES
    • METHODS OF SWITCHING
    • THE CONSUMER’S PERSPECTIVE
    • THE PHYSICIAN’S PERSPECTIVE
    • MARKETING ISSUES
    • REGULATORY ISSUES
    • ALTERNATIVE STRATEGIES TO SWITCHING
    • QUESTIONS TO DISCUSS
    • REFERENCES

    98: Costs and Pricing

    • COSTS ASSOCIATED WITH A DRUG
    • PRICING OBJECTIVES AND STRATEGIES
    • FACTORS INFLUENCING THE PRICE OF A NEW DRUG
    • DETERMINING AN APPROPRIATE PRICE TO CHARGE FOR A NEW DRUG
    • AREAS IN WHICH A PRICING STRATEGY IS REQUIRED
    • RE-EVALUATING THE PRICE OF A MARKETED DRUG
    • TESTING A PROPOSED PRICE USING MARKET RESEARCH
    • TRACKING THE SALES OF DRUGS
    • SOCIAL ISSUES REGARDING COSTS OF DRUGS
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    99: Providing Product Information to Healthcare Professionals

    • ORGANIZATIONAL LOCATION OF THE INFORMATION GROUP
    • TYPES OF QUESTIONS RECEIVED
    • RESPONDING TO QUESTIONS
    • RELATIONSHIP WITH INTERNAL COMPANY INFORMATION GROUPS
    • QUALITY ASSURANCE OF COMMUNICATION WITH EXTERNAL HEALTHCARE PROFESSIONALS
    • RESEARCH OPPORTUNITIES
    • PERSONNEL
    • ISSUES TO CONSIDER
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

SECTION 9 Functional Activities and Issues

    100: Information Management

    • TYPES OF INFORMATION IN A PHARMACEUTICAL COMPANY
    • FLOW OF INFORMATION
    • DATA MINING
    • OFFERING INFORMATION TO IN-HOUSE PROFESSIONALS
    • STORING DOCUMENTS: WHICH, WHERE, HOW LONG, HOW MANY, AND HOW CODED?
    • SELECTED USES OF COMPUTER SYSTEMS
    • ROLES OF INFORMATION MANAGERS
    • INFORMATION MANAGEMENT CHALLENGES
    • GOLDEN RULES OF INFORMATION TECHNOLOGY
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    101: Selected Statistical Issues

    • ROLES OF STATISTICS AND STATISTICIANS IN DRUG DEVELOPMENT
    • STATISTICAL ISSUES INVOLVING CLINICAL TRIALS: PRETRIAL
    • STATISTICAL ISSUES INVOLVING CLINICAL TRIALS: DURING THE TRIAL
    • STATISTICAL ISSUES INVOLVING CLINICAL TRIALS: POSTTRIAL
    • STATISTICAL ISSUES INVOLVING REGULATORY AFFAIRS AND REGULATORY AGENCIES
    • SELECTED STATISTICAL PRINCIPLES AND PRACTICES FROM A CLINICAL PERSPECTIVE
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    102: Data Management

    • THE WORLD OF DATA MANAGEMENT
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READING

    103: Toxicology Activities and Issues

    • TYPES OF DRUG TOXICITY TESTING
    • PLANNING A TOXICOLOGY PROGRAM
    • ISSUES IN STUDY DESIGN
    • REGULATORY ISSUES
    • MUTAGENICITY ISSUES
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    104: Animal Testing and Animal Welfare

    • THE CENTRAL ISSUE ABOUT PROTECTING ANIMAL RIGHTS DURING EXPERIMENTATION
    • RESPONSIBILITIES OF INSTITUTIONS CONDUCTING ANIMAL STUDIES
    • ETHICAL USE OF ANIMALS IN PHARMACEUTICAL RESEARCH
    • PRINCIPLES OF ANIMAL USE IN SCIENTIFIC RESEARCH
    • POLITICAL ISSUES
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    105: Pharmacokinetics

    • DEFINITIONS AND OBJECTIVES OF PHARMACOKINETICS
    • NEW DIRECTIONS FOR PHARMACOKINETICS OVER THE PAST DECADE
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    106: Licensing Activities and Issues

    • OVERALL CONCEPTS
    • WHAT ONE LICENSES
    • TYPES OF LICENSES
    • CREATING A LICENSING STRATEGY
    • CREATING A PROACTIVE APPROACH TO LICENSING-IN COMPOUNDS AND DRUGS
    • THE BUSINESS OF LICENSING: ORGANIZATIONAL AND METHODOLOGICAL ISSUES
    • FINANCIAL ISSUES IN LICENSING
    • LEGAL ISSUES
    • PATENT ISSUES
    • REGULATORY ISSUES
    • PROBLEMS, PRINCIPLES, AND PREDICTIONS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READING

    107: Technical Development Activities and Issues

    • INTRODUCTION
    • CHEMICAL ISSUES
    • PHARMACEUTICAL ISSUES
    • RESOURCE ISSUES
    • ANALYTICAL ISSUES
    • LIAISON ISSUES
    • “CATCH-22” SITUATIONS IN TECHNICAL DEVELOPMENT
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    108: Production Activities and Issues

    • PRODUCTION PROJECTS
    • WHAT IS PRODUCED?
    • HOW IS IT PRODUCED?
    • WHERE IS IT PRODUCED?
    • WHEN IS IT PRODUCED?
    • HOW WELL IS IT PRODUCED?—QUALITY CONTROL AND QUALITY ASSURANCE
    • HOW MUCH IS PRODUCED?
    • WHY ARE PRODUCTION COSTS SO HIGH?
    • CHALLENGES FOR PRODUCTION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    109: Patent Activities and Issues

    • WHAT IS A PATENT?
    • WHAT CAN BE PATENTED?
    • DURATION OF A PATENT
    • PROCEDURES FOR OBTAINING A PATENT
    • BASIS OF ISSUING A PATENT
    • STRUCTURING A COMPANY’S INTELLECTUAL PROPERTY PLATFORM
    • BIOTECHNOLOGY PATENTS
    • PATENTS ON ANIMALS
    • DEPOSIT ISSUES
    • “CATCH-22” SITUATIONS
    • CONFIDENTIAL INFORMATION
    • COMPULSORY LICENSES
    • GOLDEN RULES OF PATENTING AND DISCLOSURE
    • PATENT EXPIRATION
    • METHODS TO ADDRESS THE ISSUE OF PATENT EXPIRATION
    • CHOOSING AMONG THE METHODS
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READINGS

    110: Legal Activities and Issues

    • TYPES OF ACTIVITIES CONDUCTED IN A LEGAL DEPARTMENT
    • EDUCATIONAL ROLE OF LEGAL STAFF
    • ORGANIZATIONAL PLACEMENT OF LEGAL STAFF
    • PERSONNEL
    • LAWSUITS VERSUS COMPANIES
    • PRODUCT LIABILITY
    • LITIGATION ARISING FROM ACTIVITIES OF SALES REPRESENTATIVES
    • PREPARING NONLEGAL STAFF FOR PRESENTATIONS IN COURTROOM CASES
    • GOOD LEGAL PRACTICES FOR NONATTORNEYS TO FOLLOW IN A COMPANY
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    111: Financial Activities and Issues

    • CORPORATE ISSUES
    • RESEARCH AND DEVELOPMENT BUDGET
    • RESEARCH AND DEVELOPMENT EXPENDITURES
    • QUESTIONS TO DISCUSS
    • REFERENCES

SECTION 10 Overview of Current and Future Development

    112: Poor Development and Corporate Practices: Threats to a Pharmaceutical Organization

    • CORPORATE CULTURE: POOR PRACTICES AND THREATS
    • CORPORATE POLICIES: POOR PRACTICES AND THREATS
    • POOR MANAGEMENT DECISIONS AND BEHAVIOR
    • PROFESSIONAL BEHAVIOR: POOR PRACTICES AND THREATS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES

    113: Keys for Pharmaceutical and Development Success

    • AREAS ON WHICH TO FOCUS
    • KEY SUCCESS FACTORS
    • KEY CHARACTERISTICS OF THE RESEARCH AND DEVELOPMENT DIRECTOR
    • BASIC MANAGEMENT ISSUES
    • INCREASING EFFICIENCY: SELECTED EXAMPLES
    • THE NEGATIVE SPIRAL OF SUCCESS
    • KEY GOLDEN RULES
    • QUESTIONS TO DISCUSS
    • REFERENCE
    • ADDITIONAL READING

    114: Computer Simulations and Modeling

    • DEFINITIONS AND APPROACHES TO COMPUTER SIMULATIONS AND MODELING
    • TYPES OF COMPUTER SIMULATIONS AND MODELING RELATED TO DRUG DISCOVERY AND DEVELOPMENT
    • BENEFITS OF COMPUTER SIMULATIONS
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

    115: The Future of Drug Discovery and Development

    • NEAR-TERM, INTERMEDIATE-TERM, AND LONG-TERM (I.E., DISTANT) FUTURES
    • THREE APPROACHES TO PREDICTING THE DISTANT FUTURE: SCIENCE FICTION, SIMPLE EXTRAPOLATION, AND ANALYSIS OF MEGATRENDS
    • FLAWS IN MAKING PREDICTIONS ABOUT THE DISTANT FUTURE
    • VALUE OF THE PHARMACEUTICAL INDUSTRY TO SOCIETY
    • CONCLUSION
    • QUESTIONS TO DISCUSS
    • REFERENCES
    • ADDITIONAL READINGS

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

    116: Clinical Case Studies

    • CLINICAL CASE STUDY #1: PROBLEM
    • CLINICAL CASE STUDY #2: PROBLEM
    • CLINICAL CASE STUDY #3: PROBLEM
    • CLINICAL CASE STUDY #4: PROBLEM
    • CLINICAL CASE STUDY #5: PROBLEM
    • CLINICAL CASE STUDY #6: PROBLEM
    • CLINICAL CASE STUDY #7: PROBLEM
    • CLINICAL CASE STUDY #8: PROBLEM
    • CLINICAL CASE STUDY #9: PROBLEM
    • CLINICAL CASE STUDY #10: PROBLEM
    • CLINICAL CASE STUDY #11: PROBLEM
    • CLINICAL CASE STUDY #12: PROBLEM
    • CLINICAL CASE STUDY #1: RESPONSE
    • CLINICAL CASE STUDY #2: RESPONSE
    • CLINICAL CASE STUDY #3: RESPONSE
    • CLINICAL CASE STUDY #4: RESPONSE
    • CLINICAL CASE STUDY #5: RESPONSE
    • CLINICAL CASE STUDY #6: RESPONSE
    • CLINICAL CASE STUDY #7: RESPONSE
    • CLINICAL CASE STUDY #8: RESPONSE
    • CLINICAL CASE STUDY #9: RESPONSE
    • CLINICAL CASE STUDY #10: RESPONSE
    • CLINICAL CASE STUDY #11: RESPONSE
    • CLINICAL CASE STUDY #12: RESPONSE

    117: Regulatory Affairs Case Studies

    • REGULATORY CASE STUDY #1: PROBLEM
    • REGULATORY CASE STUDY #2: PROBLEM
    • REGULATORY CASE STUDY #3: PROBLEM
    • REGULATORY CASE STUDY #4: PROBLEM
    • REGULATORY CASE STUDY #5: PROBLEM
    • REGULATORY CASE STUDY #6: PROBLEM
    • REGULATORY CASE STUDY #7: PROBLEM
    • REGULATORY CASE STUDY #8: PROBLEM
    • REGULATORY CASE STUDY #9: PROBLEM
    • REGULATORY CASE STUDY #10: PROBLEM
    • REGULATORY CASE STUDY #11: PROBLEM
    • REGULATORY CASE STUDY #12: PROBLEM
    • REGULATORY CASE STUDY #1: RESPONSE
    • REGULATORY CASE STUDY #2: RESPONSE
    • REGULATORY CASE STUDY #3: RESPONSE
    • REGULATORY CASE STUDY #4: RESPONSE
    • REGULATORY CASE STUDY #5: RESPONSE
    • REGULATORY CASE STUDY #6: RESPONSE
    • REGULATORY CASE STUDY #7: RESPONSE
    • REGULATORY CASE STUDY #8: RESPONSE
    • REGULATORY CASE STUDY #9: RESPONSE
    • REGULATORY CASE STUDY #10: RESPONSE
    • REGULATORY CASE STUDY #11: RESPONSE
    • REGULATORY CASE STUDY #12: RESPONSE
    • BONUS CASE

    118: Management of Drug Development Case Studies

    • MANAGEMENT CASE STUDY #1: PROBLEM
    • MANAGEMENT CASE STUDY #2: PROBLEM
    • MANAGEMENT CASE STUDY #3: PROBLEM
    • MANAGEMENT CASE STUDY #4: PROBLEM
    • MANAGEMENT CASE STUDY #5: PROBLEM
    • MANAGEMENT CASE STUDY #6: PROBLEM
    • MANAGEMENT CASE STUDY #7: PROBLEM
    • MANAGEMENT CASE STUDY #8: PROBLEM
    • MANAGEMENT CASE STUDY #9: PROBLEM
    • MANAGEMENT CASE STUDY #10: PROBLEM
    • MANAGEMENT CASE STUDY #11: PROBLEM
    • MANAGEMENT CASE STUDY #12: PROBLEM
    • MANAGEMENT CASE STUDY #1: RESPONSE
    • MANAGEMENT CASE STUDY #2: RESPONSE
    • MANAGEMENT CASE STUDY #3: RESPONSE
    • MANAGEMENT CASE STUDY #4: RESPONSE
    • MANAGEMENT CASE STUDY #5: RESPONSE
    • MANAGEMENT CASE STUDY #6: RESPONSE
    • MANAGEMENT CASE STUDY #7: RESPONSE
    • MANAGEMENT CASE STUDY #8: RESPONSE
    • MANAGEMENT CASE STUDY #9: RESPONSE
    • MANAGEMENT CASE STUDY #10: RESPONSE
    • MANAGEMENT CASE STUDY #11: RESPONSE
    • MANAGEMENT CASE STUDY #12: RESPONSE