This book helps pharmaceutical and medical researchers better understand, design, and manage clinical trials through its industry-specific viewpoint that shows how adaptive research technology and methods benefit the drug industry. It gives readers a practical overview of drug development and advocates adaptive design approaches that allow modifications to on-going trials and improve the efficiency of trial design and the probability of success while preserving the integrity and validity of the research. This is an eye-opening reference for pharmaceutical scientists, medical researchers, and others involved in drug development.

MICHAEL J. ROSENBERG, MD, MPH, is President and Chief Executive Officer of Health Decisions, Inc. Involved in the design and execution of pharmaceutical development programs for more than twenty-five years, Dr. Rosenberg was selected as Entrepreneur of the Year by Ernst & Young (Health Sector, SE). His company's innovative applications of technology have been recognized by the CIO Enterprise Value Award and the Cisco Growing with Technology Award. Health Decisions has also been named three times to the Deloitte & Touche Technology Fast 500 and the Inc. 500. Dr. Rosenberg is the author of more than 150 scientific articles and serves on advisory groups in business, technology, and medicine.

Acknowledgements
Forward
Opportunity for Efficiency
The Adaptive Solution
An Industrial Success Story
Signs of Trouble Ahead
Converging Challenges
The Struggle to Replace Lost Revenues
Clinical Research is the Key
Behind the High Costs of Clinical Development
High Costs and Increasing Prices
Growing Pressures Mandate Greater Efficiency
The High Risk of Current Development Practices
Economic Consequences of Faster Clinical Development
Thriving in a New Era
Defining and Extending the Adaptive Approach
The Adaptive Concept
Knowledge, Time and Decision-Making
The Value of Early Knowledge
The Spectrum of Design and Operational Adaptations
Maximizing the Adaptive Approach: Agile Clinical Development
Measure Performance in Real-time
Metrics in Action
Right Information to the Right Eyes at the Right Time
Make Timely Decisions
Organize Work in Lean Processes
Rework in Clinical Studies
Backflow of Patient Data
Match Technology with Tasks
Objections to Adaptive Methods
Integrity and Validity
The Regulatory Environment
The Complexity of Clinical Research
Conclusion
Design Adaptations Part One: Finding the Right Dose
Background
Types of Design Adaptations
Order of Discussion
Dosing Nomenclature
etermining Maximum Safe Dose
Single Arm
Continual Reassessment Method
Other Bayesian Dose-Finding Methods
Determining Optimal Dose (Pruning)
Multiple Arms
Improvements over Conventional Approaches to Dose Finding
Dose Selection in Practice
Optimizing Dose Selection
Minimizing Costs vs. Maximizing Information
Surrogate Endpoints
Conclusion
Design Adaptations Part Two: Additional Design Changes
Sample-Size Reestimation
The Trouble with Planning Estimates
The High Cost of "Underbuilt" Studies
The Benefits of Reestimation and Rightsizing
Reestimation and Trial Stages
Rules to Restrict Reestimation
Adjusting Sample Size for Nuisance Parameters
Seamless Designs: Combining Multiple Phases
When to Consider Seamless Studies
Seamless Phase I/Phase II Trials
Seamless Phase II/Phase III Trials
Planning Issues in Seamless Trials
Phase I-II-III Designs
Adaptive Randomization
Response-Adaptive Randomization
Other Forms of Adaptive Randomization
Other Types of Design Adaptations
Noninferiority-to-Superiority Design
Adaptive Hypotheses and Subpopulations
Treatment Switching
Conclusions
Operational Adaptations
Design and Operational Adaptations
The Nature and Significance of Operational Adaptations
Implementing Operational Adaptations
Enrollment and Other Site Issues
Data Quality
Monitoring
Site Closeout and Database Lock
Supporting Functions for Efficient Operations
The Bottom Line
Agile Clinical Development
Benefits of Agile Development
A Development Example
Program Planning
Safety Testing (Phase I)
Design
Planning
Operational Considerations
Putting the Plan into Action
Benefits Realized
Transition to Dose-Finding Study
Dose Finding (Phase II)
Design
Planning
Operational Considerations
Putting the Plan into Action
Benefits Realized
Transition to Confirmatory Studies
Confirmatory Testing (Phase III)
Design
Planning
Operational
Putting the Plan into Action
Benefits Realized
Transition to Regulatory Filings
Summing Up: The Power of Agile Development
Planning Adaptive Programs
Determining Design Adaptations and their Requirements
Determining Operational Requirements to Support Design Adaptations
Ensuring the Ability to Meet Operational Requirements
The Importance of Programmatic Thinking
Looking Ahead
Advisory and Oversight Groups
Optimizing the Planning Process
Regulatory Discussions
Contingency Planning
Planning Tools and Techniques
Decision Trees
Simulation
Uncertainties in Clinical Research
Simulation Tools
Simulation Step by Step
The Limitations of Simulation
Conclusions
Statistics and Decision Making in Adaptive Research
The Frequentist Approach
What Frequentist Results Say about the Results of a Clinical Study
Using Frequentist Results to Make Decisions Based on Individual Trials
Other Issues with Frequentist Methods
The Bayesian Approach
Prior Distributions
How Bayesian Statistics Works
Bayesian Statistics in the Real World
Bayesian Methods in Clinical Research
Comparing Bayesian and Frequentist Methods.\
Prior Distributions
The Pharma Context
Learning and Confirming
Ethical and Operational Issues
Regulatory Considerations
Conclusions
Frequentists, Bayesians, and Pragmatists
The Agile Platform
Essential Types of Data
Management Cycles in Clinical Studies
The Common Platform for Design and Operational Adaptations
Data Capture
Data-Capture Technologies
The First Generation
The Second Generation
The Third Generation
Data Cleaning and Validation Technology
Data Analysis Tools
Randomization
Site Management
Supply-Chain Management
Communications
Conclusions
The Future of Clinical Development
Is Restructuring an Alternative to Improving Clinical Development?
Greater Efficiency: Changes that Everyone Can Applaud
Biotechs and Emerging Low-Cost Competitors
Globalization, Offshoring, and Outsourcing
Managing More Complex Trials
Individualized Medicine Demands Greater Efficiency
A More Important Role for Postmarketing Studies
The Reward for Greater Efficiency
Financial Implications of the Agile Approach
Financial Implications of the Agile Approach for the Drug Industry
A Brighter Future for Clinical Development
First Steps toward Agile Development
A Eight-Point Program for Embracing the Adaptive Approach
Table of Contents provided by Publisher. All Rights Reserved.

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The Agile Approach to Adaptive Research Optimizing Efficiency in Clinical Development

9780470247518

0470247517

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