520notes - ST 520 Statistical Principles of Clinical Trials...

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Unformatted text preview: ST 520 Statistical Principles of Clinical Trials Lecture Notes (Modified from Dr. A. Tsiatis’ Lecture Notes) Daowen Zhang Department of Statistics North Carolina State University c circlecopyrt 2009 by Anastasios A. Tsiatis and Daowen Zhang TABLE OF CONTENTS ST 520, A. Tsiatis and D. Zhang Contents 1 Introduction 1 1.1 Scope and objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Brief Introduction to Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . 2 1.3 Brief Introduction and History of Clinical Trials . . . . . . . . . . . . . . . . . . . 12 2 Phase I and II clinical trials 18 2.1 Phases of Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 2.2 Phase II clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 2.2.1 Statistical Issues and Methods . . . . . . . . . . . . . . . . . . . . . . . . . 21 2.2.2 Gehan’s Two-Stage Design . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 2.2.3 Simon’s Two-Stage Design . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 3 Phase III Clinical Trials 35 3.1 Why are clinical trials needed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 3.2 Issues to consider before designing a clinical trial . . . . . . . . . . . . . . . . . . 36 3.3 Ethical Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 3.4 The Randomized Clinical Trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 3.5 Review of Conditional Expectation and Conditional Variance . . . . . . . . . . . . 43 4 Randomization 49 4.1 Design-based Inference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 4.2 Fixed Allocation Randomization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 4.2.1 Simple Randomization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 4.2.2 Permuted block randomization . . . . . . . . . . . . . . . . . . . . . . . . . 57 4.2.3 Stratified Randomization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 4.3 Adaptive Randomization Procedures . . . . . . . . . . . . . . . . . . . . . . . . . 66 4.3.1 Efron biased coin design . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 4.3.2 Urn Model (L.J. Wei) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 4.3.3 Minimization Method of Pocock and Simon . . . . . . . . . . . . . . . . . 67 i TABLE OF CONTENTS ST 520, A. Tsiatis and D. Zhang 4.4 Response Adaptive Randomization . . . . . . . . . . . . . . . . . . . . . . . . . . 70 4.5 Mechanics of Randomization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 5 Some Additional Issues in Phase III Clinical Trials 74 5.1 Blinding and Placebos . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 5.2 Ethics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 5.3 The Protocol Document . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 775....
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This note was uploaded on 05/02/2010 for the course BIOSTAT ST520 taught by Professor Kim during the Spring '10 term at Yonsei University.

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520notes - ST 520 Statistical Principles of Clinical Trials...

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