Data Monitoring Committee Training Lecture Three: Methods Overview - PDF document

Data Monitoring Committee Training Lecture Three: Methods Overview Introduction 1.1 Statistical Methods Overview 1.2 Book References

1.3 DMC Structure and Function Review 1.4 Data Monitoring Rationale

1.5 DMC Recommendations 1.6 Reasons for Early Termination

1.7 DMC Decision Factors 1.8 DMC Summary - NIH Model

1.9 DMC Summary - Independence 1.10 Statistical Challenges

2. Motivating Example 2.1 Statistical Methods - Motivating Example 2.2 The Beta-blocker Heart Attack Trial

2.3 BHAT: Accumulating Survival Data 2.4 BHAT: Mortality Curves

2.5 BHAT: Baseline Comparisons 2.6 BHAT: Total Mortality by Subgroup

2.7 BHAT: Total Mortality by Risk Group 2.8 DMC Interim Analysis Challenge

2.9 Coronary Drug Project 2.10 Coronary Drug Project Research Group

2.11 Repeated Significance Testing 3. Two Monitoring Methods 3.1 Statistical Methods Overview

3.2 Group Sequential Boundaries 3.3 Three Common Boundaries

3.4 Haybittle-Peto 3.5 Armitage-Pocock

3.6 Group Sequential Model 3.7 Summary Statistics Explained

3.8 Sample Size Implications 3.9 Pocock Group Sequential Boundaries

3.10 Sample Size Example for Pocock 3. 11 O’Brien -Fleming Group Sequential Boundary

3. 12 O’Brien -Fleming Group Sequential Boundaries cont'd 3.13 Fixed Design Sample Size

3.14 Defining Assessment Target 3.15 International Use of Boundaries

3. 16 Boundary Parameter ∆ for Pocock & OBF 3.17 Selection of Group Sequential Boundaries

3.18 Group Sequential Boundaries 3.19 BHAT Example

3.20 BHAT GSB 3.21 Timing of Data Reviews

3.22 Using Alpha Spending Function 3.23 Information and Calendar Time

3.24 Alpha Spending 3.25 Boundary Crossing Probability

3.26 Alpha Spent For 5 Interim Analyses 3.27 OBF Alpha Spending Function

3.28 Examples of a*(t) 3.29 Why Is Flexibility Important?

3.30 CAST GSB 3.31 CAST Interim Data: Sudden Death

3.32 CAST Sequential Boundaries 3.33 Lessons of CAST

3.34 Symmetric or Asymmetric GSBs 4. Negative Trends 4.1 Statistical Methods Overview

4.2 Methods for Assessing Negative Trends 4.3 Group Sequential Boundaries For Negative Trends

4.4 Motivating Example: VEST 4.5 Vesnarinone (VEST) in Heart Failure

4.6 Vesnarinone Doses 4.7 Vesnarinone Mortality and Morbidity

4.8 Vesnarinone Second Trial 4.9 VEST NEJM 1998

4.10 VEST: Survival in the Three Groups 4.11 VEST: Mortality By Subgroups

4.12 VEST: Accumulating Mortality Results 4.13 VEST Mortality High Dose vs. Placebo

4.14 Why Did VEST Continue? 4.15 Conditional Power

4.16 Conditional Power cont'd 4.17 Conditional Power In General

4.18 A Method for Computing 4.19 Visual Aid

4.20 Conditional Power Parameter ϴ 4.21 Conditional Power Parameter cont'd

4.22 Conditional Power Table 4.23 Conditional Power Boundaries

4.24 Symmetric Vs. Asymmetric Boundaries 5. Methods Summary 5.1 Sequential Methods Summary

5.2 Group Sequential Software 5.3 References page 1

5.4 References page 2 5.5 References page 3

5.6 End of Lecture Three