Innovations and Trends in Clinical Trials: Microdosing (Phase 0 Trials), Adaptive Trials, Phase IV Trials and the Role of Information Technology

Table of Contents

1.Methodology and Executive Summary

• 1.1 Report Objectives
• 1.2 Report Methodology
• 1.3 Executive Summary
  • 1.3.1 Microdosing
  • 1.3.2 Adaptive Design
  • 1.3.3 Phase IV Post Marketing Trials
  • 1.3.4 Information Technology
  • 1.3.5 Clinical Trials Outlook

2. Clinical Trials - “ Background”

• 2.1 Introduction to Clinical Trials
• 2.2 Clinical Trials Marketplace
• 2.3 Types of Clinical Trials
• 2.4 Phases of Clinical Trials
• 2.5 Brief History of Clinical Trials
• 2.6 Need for Innovation in the Pharmaceutical Industry
• 2.7 Need for Maximization of Drug Development
• 2.8 Major Limitations of Present Clinical Trial Designs
  • 2.8.1 Cost
  • 2.8.2 Inflexibility
  • 2.8.3 Time
  • 2.8.4 Use of Animals
  • 2.8.5 Early Trial Failures
  • 2.8.6 Pharmacogenomics

3. Clinical Trials - “ Overview of New Developments”

• 3.1 Present Situation
• 3.2 Regulatory Environment
• 3.3 Need for Changes
• 3.4 Likely Future Trends in Clinical Trials
• 3.5 Partnerships in the Realm of Clinical Trials

4. Phase 0 Clinical Trials

• 4.1 Overview
• 4.2 Human Microdosing - Technology
  • 4.2.1 Accelerator Mass Spectometry (AMS)
    • 4.2.1.1 Key Study Details
  • 4.2.2 Positron Emission Tomography (PET)
    • 4.2.2.1 Key Study Details
  • 4.2.3 Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS)
  • 4.2.4 Liquid Scintillation Counting (LSC)
    • 4.2.4.1 Key Study Details
• 4.3 Regulatory Issues
• 4.4 Recent Changes in Regulatory Environment
• 4.5 Microdosing Versus Conventional Clinical Trial Methods - Advantages and Disadvantages
• 4.6 Microdosing and the Use of Animals
• 4.7 Examples of Phase 0 Clinical Trials
  • 4.7.1 Neurocrine Biosciences
    • 4.7.1.1 Key Study Details
  • 4.7.2 Radiant Research
    • 4.7.2.1 Key Study Details
  • 4.7.3 Resverlogix
    • 4.7.3.1 Key Study Details
  • 4.7.4 Speedel Pharmaceuticals
    • 4.7.4.1 Key Study Details
  • 4.7.5 Tripep
    • 4.7.5.1 Key Study Details
  • 4.7.6 Vitalea Science
    • 4.7.6.1 Key Study Details
  • 4.7.7 Xceleron
    • 4.7.7.1 Key Study Details
• 4.8 Future of Phase 0 Clinical Trials

5. Adaptive Trials

• 5.1 Overview
• 5.2 Forms of Adaptive Trials
  • 5.2.1 Scientifically Predetermined Outcome
  • 5.2.2 Continual Reassessment Method (CRM)
  • 5.2.3 Adaptive Randomization
  • 5.2.4 Group Sequential Trial
• 5.3 Regulatory Issues
• 5.4 Recent Examples of Adaptive Trials
• 5.5 Adaptive Versus Controlled Clinical Trials - “ Advantages and Disadvantages”
• 5.6 Future of Adaptive Clinical Trials
• 5.7 Adaptive Clinical Trials - Company Overviews
  • 5.7.1 Bristol-Myers Squibb (BMS)
  • 5.7.2 Eli Lilly
  • 5.7.3 Novartis
  • 5.7.4 Pfizer
  • 5.7.5 Tessella
  • 5.7.6 Wyeth

6. Phase IV Clinical Trials

• 6.1 Overview
• 6.2 Regulatory Issues
  • 6.2.1 Completion of Promised Post-Marketing Studies
  • 6.2.2 Clinical Trials Registries
  • 6.2.3 Results Disclosure
• 6.3 Examples of Comparative Phase IV Studies
  • 6.3.1 Strattera
  • 6.3.2 Magnex
  • 6.3.3 Avonex
• 6.4 Examples of Indication Extension Phase IV Studies
  • 6.4.1 Remicade
  • 6.4.2 Velcade
  • 6.4.3 Humira
  • 6.4.4 Visicol
• 6.5 Examples of Product Withdrawals Following Phase IV Studies
  • 6.5.1 Lipobay/Baycol
  • 6.5.2 Rezulin
  • 6.5.3 Vioxx
• 6.6 Future of Phase IV Trials

7. Information Technology in Clinical Trials

• 7.1 Overview
• 7.2 Regulatory Developments
• 7.3 Benefits of Information Technology
• 7.4 Examples of IT in Clinical Trials
• 7.5 Electronic Data Capture (EDC)
  • 7.5.1 Market Value and Potential
  • 7.5.2 Main Benefits of EDC
  • 7.5.3 Key Therapeutic Areas for EDC Application
  • 7.5.4 Companies Using EDC
• 7.6 Clinical Trials Management System (CTMS)
  • 7.6.1 Advantages and Disadvantages of CTMS
  • 7.6.2 Companies Developing CTMS
• 7.7 Clinical Data Management System (CDMS)
  • 7.7.1 CDMS Subtypes
    • 7.7.1.1 Database Management System (DBMS)
    • 7.7.1.2 Case Report Form (CRF) Designs
    • 7.7.1.3 Data Entry Interface
    • 7.7.1.4 Reporting/Analysis
  • 7.7.2 Companies Involved in CDMS Design
• 7.8 Clinical Trials and the Internet
• 7.9 Security, Confidentiality and Ethical Concerns

8. Company Profiles

• 8.1 Pharmaceutical Companies
  • 8.1.1 Bayer
  • 8.1.2 Bristol-Myers Squibb (BMS)
  • 8.1.3 Eli Lilly
  • 8.1.4 InKine Pharmaceuticals
  • 8.1.5 Johnson & Johnson (J&J)
  • 8.1.6 Merck & Co
  • 8.1.7 Novartis
  • 8.1.8 Pfizer
  • 8.1.9 Wyeth
• 8.2 Biopharmaceutical Companies
  • 8.2.1 Biogen Idec
  • 8.2.2 Cambridge Antibody Technology (CAT)
  • 8.2.3 Millennium
  • 8.2.4 Neurocrine Biosciences
  • 8.2.5 Pharmaceutical Profiles
  • 8.2.6 Radiant Research
  • 8.2.7 Resverlogix Corporation
  • 8.2.8 Speedel Pharmaceuticals
  • 8.2.9 Tripep AB
  • 8.2.10 Vitalea Science
  • 8.2.11 Xceleron
• 8.3 Medical Device Companies
  • 8.3.1 Asthmatx
• 8.4 Pharmaceutical Software Companies
  • 8.4.1 DATATRAK
  • 8.4.2 etrials
  • 8.4.3 Phase Forward
  • 8.4.4 Tessella Support Services

Glossary of Terms

Appendix : Regulatory Guidance

• Table 2.1 Types of Phase I Trials
• Table 2.2 Phases of Clinical Trials
• Table 2.3 Total Expected Sample Sizes for Alternative Clinical Research Programs
• Table 2.4 Regulatory Agencies for Pharmaceutical Products in Major Global Markets
• Table 2.5 Areas of Animal Use
• Table 4.1 Advantages and Disadvantages of AMS
• Table 4.2 Advantages and Disadvantages of Human Microdosing
• Table 4.3 Benefits of Microdosing in Relation to Studies on Animals
• Table 4.4 Drugs Tested with Human Microdosing in the CREAM Trial
• Table 5.1 Advantages and Disadvantages of Adaptive Clinical Trials
• Table 7.1 IT in Clinical Trials
• Table 7.6 Examples of Applying IT to Improve Clinical Trials Performance
• Table 7.3 Improvement of Process and Increase of Business Value through the Adoption of e-Solutions
• Table 7.4 Technology Map for Clinical Trials
• Table 7.5 Benefits of IT in Clinical Trials
• Table 7.2 Reasons Cited for Not Adopting New Data Collection Methods

• Graph 2.1 Decreasing R&D Productivity
• Graph 2.2 R&D Costs and Research Productivity
• Graph 4.1 Semilogarithmic Plot of the Plasma Concentration/Time Profile of Midazolam
• Graph 7.1 Impact of Technology on Clinical Trials
• Graph 7.2 Cost Comparisons (in US$mn) of EDC Budgets of Four Clinical Trials with
• Corresponding Paper Model and EDC L2TTP
• Graph 7.3 Comparison of Efficiency of EDC versus Paper Data Collection

• Figure 2.1 Overview of the Activities Involved in Modern Drug Discovery and Development
• Figure 2.2 Phases of Pre-clinical and Clinical Development
• Figure 5.1 Graphic Representation of Adaptive Trial Design
• Figure 5.2 Re-Analysis of Pravachol Pac Clinical Trial Using Bayesian Techniques
• Figure 7.1 Typical Systems That Can Be Integrated with CTMS