Part 1: Some History begins with Chapter 1: The Goal of Science, which includes subtopics 1.1 Cause-and-Effect, 1.2 The Light Switch, 1.3 Clinical Trials as Scientific Experiments, 1.4 The Treatment Effect(s), 1.5 The Crucial Equivalence, and 1.6 Summary So Far. Chapter 2: How Did We Get Here? covers 2.1 Some History of Clinical Research, 2.2 Statistics and Clinical Research, 2.3 The University Group Diabetes Program (UGDP), 2.4 More Statistical Rigor, 2.5 Intent to Treat as the Default Standard, 2.6 The National Research Council Report on Missing Data, 2.7 The Estimand, 2.8 Dapagliflozin and the FDA Advisory Committee Meeting, 2.9 Estimands â" Broadening the Perspective, 2.10 The Stuff of Life, and 2.11 Summary So Far. Chapter 3: ICH E9(R1) Addendum on Estimands includes 3.1 What is the Question? An Example, 3.2 Another Example: Alzheimerâs Disease, and 3.3 Causal Inference. Part 2: ICH E9(R1) Explained begins with Chapter 4: The Four Attributes, which includes 4.1 Background, 4.2 Intercurrents Events, 4.3 Attribute 1: What Is the Treatment?, 4.4 Examples of Treatment Descriptions in the Medical Literature, 4.5 The Estimand-Defined Study Treatment, 4.6 A (Very Big) Missed Piece, 4.7 What Is the Treatment Effect Questions?, 4.8 Attribute 2: What is the Population?, 4.9 Attribute 3: What is the Variable?, 4.10 Attribute 4: What Is the Population-level Summary Measure, and 4.11 Summary. Chapter 5: The Five Strategies for Intercurrent Events includes 5.1 A Thought Experiment, 5.2 Some Early Commentary on the ITT Approach, 5.3 Summary So Far, 5.4 The Five Strategies, 5.5 Incomplete Data and Intercurrent Events, 5.6 Somethinâs Gotta Give, 5.7 Strategic Thinking, and 5.8 Summary. Chapter 6: The Tripartite Estimand Approach includes 6.1 Mixture Distribution, 6.2 An Illustrative Example, 6.3 The Tripartite Estimand Approach (TEA), 6.4 Visualization, and 6.5 Summary. Part 3: Weaving the Golden Thread begins with Chapter 7: Implementation of the Estimand Framework, which includes 7.1 The Story So Far, 7.2 The Succinct Estimand Framework, 7.3 An Illustrative Example Based in Reality, and 7.4 Summary. Chapter 8: Examples of the Golden Thread includes 8.1 Preamble, 8.2 Example 1: Covid-19 â" A Vaccine Strategy, 8.3 Example 2: Graft versus Host Disease (GVHD), 8.4 Example 3: Major Depressive Disorder, 8.5 Example 4: Hepatocellular Carcinoma, 8.6 Example 5: Age-Related Macular Degeneration, and 8.7 Example 6: Chimeric Antigen Receptor T-cell Therapy. Part 4: Epistemology - What is the Truth? begins with Chapter 9: What Do We Mean by the Mean?, which includes 9.1 Suppose We Knew the Truth, 9.2 In Search of the Truth!, 9.3 What Do We Mean by the Null Hypothesis?, and 9.4 Summary. Chapter 10: Potential Explanations of the Estimand includes 10.1 Background, 10.2 Potential Outcomes, 10.3 Principal Stratification, 10.4 The Connection to ICH E9(R1), 10.5 The Tripartite Estimand Approach, and 10.6 Summary. The Epilogue includes Chapter 11: Epilogue, with subtopics 11.1 Principles, 11.2 Process, 11.3 Practicalities, and 11.4 Progress, followed by References.
