The Architecture of Evidence
Dr. Evelyn Sato
LeMay Publishing
MEDICAL
The Architecture of Evidence
Clinical Trials21,486 words76 chapters
Published by LeMay Publishing. 21,486 words across 76 chapters.
About This Publication
Principles and practice of modern clinical trial design, from adaptive protocols to Bayesian interim analysis, examining how the most powerful instrument of evidence-based medicine can be optimized for contemporary practice.
Published by LeMay Publishing, a division of LeMay. Massachusetts.
ISBN: 979-8-0000-7028-4
Chapters
1THE ARCHITECTURE OF EVIDENCE
2Principles and Practice of Modern Clinical Trial Design: From Adaptive Protocols to Bayesian Interim Analysis
3ABOUT THE AUTHOR
4PREFACE
5TABLE OF CONTENTS
6CHAPTER 1
7FOUNDATIONS OF CLINICAL EVIDENCE
81.1 The Epistemology of Clinical Proof
91.2 Historical Evolution of the Controlled Experiment
101.3 The Hierarchy of Evidence Revisited
111.4 Ethical Imperatives in Trial Design
121.5 Regulatory Frameworks and Evidentiary Standards
13CHAPTER 2
14THE CLASSICAL RANDOMIZED CONTROLLED TRIAL
152.1 Anatomy of the Fixed Design
162.2 Randomization: Theory and Implementation
172.3 Blinding and Its Boundaries
182.4 Sample Size Determination and Power Analysis
192.5 Frequentist Hypothesis Testing and Its Limitations
202.6 The Intention-to-Treat Principle and Missing Data
21CHAPTER 3
22ADAPTIVE TRIAL DESIGNS — PRINCIPLES AND TAXONOMY
233.1 Defining Adaptivity in Clinical Trials
243.2 Taxonomy of Adaptive Designs
253.3 The Regulatory Landscape for Adaptive Trials
263.4 Sample Size Re-estimation
273.5 Response-Adaptive Randomization
283.6 Adaptive Dose-Finding Designs
293.7 Seamless Phase II/III Designs
303.8 Operational Considerations and Implementation
31CHAPTER 4
32GROUP SEQUENTIAL METHODS AND INTERIM ANALYSIS
334.1 The Rationale for Interim Monitoring
344.2 Repeated Significance Testing and Alpha Spending
354.3 The Pocock and O'Brien-Fleming Boundaries
364.4 The Lan-DeMets Alpha-Spending Function
374.5 Futility Boundaries and Conditional Power
384.6 Information Fractions and Timing of Analyses
394.7 Data Safety Monitoring Boards: Structure and Function
40CHAPTER 5
41BAYESIAN METHODS IN CLINICAL TRIALS
425.1 The Bayesian Paradigm: Philosophy and Foundations
435.2 Prior Specification: Informative, Weakly Informative, and Non-informative
445.3 Posterior Inference and Credible Intervals
455.4 Bayesian Adaptive Randomization
465.5 Bayesian Interim Analysis and Decision Rules
475.6 Bayesian Sample Size Determination
485.7 Bayesian Hierarchical Models in Multi-Center Trials
495.8 Regulatory Acceptance of Bayesian Designs
505.9 Computational Methods: MCMC and Beyond
51CHAPTER 6
52MASTER PROTOCOLS — PLATFORM, BASKET, AND UMBRELLA TRIALS
536.1 The Concept of the Master Protocol
546.2 Platform Trials: Perpetual Learning Architectures
556.3 Basket Trials: Histology-Agnostic Investigation
566.4 Umbrella Trials: Biomarker-Driven Stratification
576.5 Statistical Considerations in Master Protocols
586.6 Governance, Infrastructure, and Operational Complexity
596.7 Lessons from RECOVERY, I-SPY 2, and NCI-MATCH
60CHAPTER 7
61EMERGING PARADIGMS AND THE FUTURE OF TRIAL DESIGN
627.1 Decentralized and Hybrid Clinical Trials
637.2 Digital Biomarkers and Wearable-Derived Endpoints
647.3 Synthetic Control Arms and Real-World Evidence Integration
657.4 Machine Learning in Trial Design and Conduct
667.5 Regulatory Science and the Evolving Evidentiary Standard
677.6 The Ethics of Innovation in Trial Methodology
68CHAPTER 8
69SYNTHESIS — DESIGNING THE MODERN CLINICAL TRIAL
708.1 Matching Design to Scientific Question
718.2 A Decision Framework for Design Selection
728.3 The Interdisciplinary Design Team
738.4 Case Studies in Integrated Design
748.5 Toward an Architecture of Evidence
75BIBLIOGRAPHY
76INDEX