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

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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


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Data Monitoring Committee Training Lecture Three: Methods Overview Introduction

1.1 Statistical Methods Overview 1.2 Book References

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1.3 DMC Structure and Function Review 1.4 Data Monitoring Rationale

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1.5 DMC Recommendations 1.6 Reasons for Early Termination

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1.7 DMC Decision Factors 1.8 DMC Summary - NIH Model

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1.9 DMC Summary - Independence 1.10 Statistical Challenges

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  • 2. Motivating Example

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

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2.3 BHAT: Accumulating Survival Data 2.4 BHAT: Mortality Curves

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

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

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2.9 Coronary Drug Project 2.10 Coronary Drug Project Research Group

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2.11 Repeated Significance Testing

  • 3. Two Monitoring Methods

3.1 Statistical Methods Overview

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3.2 Group Sequential Boundaries 3.3 Three Common Boundaries

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3.4 Haybittle-Peto 3.5 Armitage-Pocock

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3.6 Group Sequential Model 3.7 Summary Statistics Explained

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3.8 Sample Size Implications 3.9 Pocock Group Sequential Boundaries

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3.10 Sample Size Example for Pocock 3.11 O’Brien-Fleming Group Sequential Boundary

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

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3.14 Defining Assessment Target 3.15 International Use of Boundaries

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3.16 Boundary Parameter ∆ for Pocock & OBF 3.17 Selection of Group Sequential Boundaries

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3.18 Group Sequential Boundaries 3.19 BHAT Example

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3.20 BHAT GSB 3.21 Timing of Data Reviews

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3.22 Using Alpha Spending Function 3.23 Information and Calendar Time

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3.24 Alpha Spending 3.25 Boundary Crossing Probability

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

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

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3.30 CAST GSB 3.31 CAST Interim Data: Sudden Death

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3.32 CAST Sequential Boundaries 3.33 Lessons of CAST

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3.34 Symmetric or Asymmetric GSBs

  • 4. Negative Trends

4.1 Statistical Methods Overview

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

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

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4.6 Vesnarinone Doses 4.7 Vesnarinone Mortality and Morbidity

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4.8 Vesnarinone Second Trial 4.9 VEST NEJM 1998

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

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

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4.14 Why Did VEST Continue? 4.15 Conditional Power

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4.16 Conditional Power cont'd 4.17 Conditional Power In General

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4.18 A Method for Computing 4.19 Visual Aid

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

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4.22 Conditional Power Table 4.23 Conditional Power Boundaries

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4.24 Symmetric Vs. Asymmetric Boundaries

  • 5. Methods Summary

5.1 Sequential Methods Summary

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5.2 Group Sequential Software 5.3 References page 1

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5.4 References page 2 5.5 References page 3

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5.6 End of Lecture Three