Innovative Statistics in Regulatory Science (Hardcover)

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