Innovative Statistics in Regulatory Science

Preface 
1.  Introduction
    Introduction
    Key Statistical Concepts
    Complex Innovative Designs
    Practical, Challenging, and Controversial Issues
    Aim and Scope of the Book
2.  Totality-of-the-Evidence 
    Introduction
    Substantial Evidence
    Totality-of-the-evidence
    Practical and Challenging Issues
    Development of Index for Totality-of-the-Evidence
    Concluding Remarks
3. Hypotheses Testing Versus Confidence Interval 
    Introduction
    Hypotheses Testing 
    Confidence Interval Approach
    Two One-sided Tests Procedure and Confidence Interval Approach
    A Comparison
    Sample Size Requirement 
    Concluding Remarks
    Appendix of Chapter 3
4. Endpoint Selection
    Introduction
    Clinical Strategy for Endpoint Selection
    Translations Among Clinical Endpoints
    Comparison of Different Clinical Strategies
    A Numerical Study
    Development of Therapeutic Index Function
    Concluding Remarks
5. Non-inferiority Margin 
    Introduction
    Non-inferiority Versus Equivalence
    Non-inferiority Hypotheses 
    Methods for Selection of Non-inferiority Margin 
    Strategy for Margin Selection
    Concluding Remarks
6. Missing Data
    Introduction
    Missing Data Imputation 
    Marginal/Conditional Imputation for Contingency 
    Test for Independence
    Recent Development 
    Concluding Remarks
7.  Multiplicity
    General Concepts
    Regulatory Perspective and Controversial Issues 
    Statistical Methods for Multiplicity Adjustment 
    Gate-keeping Procedures
    Concluding Remarks
8. Sample Size 
    Introduction
    Traditional Sample Size Calculation
    Selection of Study Endpoints
    Multiple-Stage Adaptive Designs 
    Adjustment with Protocol Amendments 
    Multi-Regional Clinical Trials
    Current Issues 
    Concluding Remarks
9. Reproducible Research
    Introduction
    The Concept of Reproducibility Probability
    The Estimated Power Approach
    Alternative Methods for Evaluation of Reproducibility Probability
    Applications
    Future Perspectives
10. Extrapolation
    Introduction
    Shift in Target Patient Population
    Assessment of Sensitivity Index
    Statistical Inference
    An Example
    Concluding Remarks
    Appendix of Chapter 10
11. Consistency Evaluation
    Introduction
    Issues in Multi-regional Clinical Trials
    Statistical Methods 
    Simulation Study
    An Example
    Other Considerations/Discussions 
    Concluding Remarks
12.  Drug Products with Multiple Components 
    Introduction
    Fundamental Differences
    Basic Considerations
    TCM Drug Development
    Challenging Issues
    Recent Development 
    Concluding Remarks
13. Adaptive Trial Design 
    Introduction
    What Is Adaptive Design
    Regulatory/Statistical Perspectives
    Impact, Challenges, and Obstacles
    Some Examples 
    Strategies for Clinical Development
    Concluding Remarks
14. Selection Criteria in Adaptive Dose Finding
    Introduction
    Criteria for Dose Selection
    Practical Implementation and Example
    Clinical Trial Simulations 
    Concluding Remarks
15. Generic Drugs and Biosimilars
    Introduction
    Fundamental Differences
    Quantitative Evaluation of Generic Drugs
    Quantitative Evaluation of Biosimilars 
    General Approach for Assessment of Bioequivalence/Biosimilarity 
    Scientific Factors and Practical Issues
    Concluding Remarks
16. Precision and Personalized Medicine
    Introduction
    The Concept of Precision Medicine
    Design and Analysis of Precision Medicine
    Alternative Enrichment Designs 
    Concluding Remarks
17. Big Data Analytics
    Introduction
    Basic Considerations
    Types of Big Data Analytics
    Bias of Big Data Analytics
    Statistical Methods for Estimation of ∆ and μP - μN  
    Concluding Remarks
18. Rare Disease Drug Development
    Introduction
    Basic Considerations
    Innovative Trial Designs
    Statistical Methods for Data Analysis
    Evaluation of Rare Disease Clinical Trials
    Some Proposals for Regulatory Consideration
    Concluding Remarks
References
Subject Index