Design and Analysis of Experiments in the Health Sciences

GERALD VAN BELLE, PhD, is Professor Emeritus in the Departments of Biostatistics and Environmental and Occupational Health Sciences at the University of Washington. A Fellow of the American Statistical Association and the American Association for the Advancement of Science, he has published more than 140 articles in the areas of experimental design and data characterization as well as analysis with application to neurodegenerative diseases, effects of air pollution on health and toxicology, and clinical trials in resuscitation outcomes research. KATHLEEN F. KERR, PhD, is Associate Professor of Biostatistics at the University of Washington. A former Burroughs Wellcome postdoctoral fellow in mathematics and molecular biology, Dr. Kerr currently serves as associate editor of PLoS Genetics and Statistical Applications in Genetics and Molecular Biology. Her research interests include gene expression microarrays, statistical genetics, experimental design, and biomarker research.

Preface xiii 1. The Basics 1 1.1 Four Basic Questions 1 1.2 Variation 5 1.3 Principles of Design and Analysis 6 1.4 Experiments and observational studies 11 1.5 Illustrative applications of principles 14 1.6 Experiments in the health sciences 15 1.7 Adaptive Allocation 19 1.8 Sample Size Calculations 23 1.9 Statistical models for the data 25 1.10 Analysis and presentation 27 1.11 Notes 31 1.12 Summary 33 1.13 Problems 34 2. Completely Randomized Experiments 41 2.1 Randomization 42 2.2 Hypotheses and Sample Size 42 2.3 Estimation and Analysis 43 2.4 Example 44 2.5 Discussion and Extensions 46 2.6 Randomization 54 2.7 Hypotheses and Sample Size 54 2.8 Estimation and Analysis 54 2.9 Example 55 2.10 Discussion and Extensions 59 2.11 Notes 61 2.12 Summary 70 2.13 Problems 70 3. Randomized Block Designs 83 3.1 Randomization 84 3.2 Hypotheses and Sample Size 84 3.3 Estimation and Analysis 85 3.4 Example 85 3.5 Discussion and Extensions 89 3.6 Randomization 99 3.7 Hypotheses and Sample Size 99 3.8 Estimation and Analysis 99 3.9 Example 100 3.10 Discussion and Extensions 102 3.11 Randomization 104 3.12 Hypotheses and Sample Size 104 3.13 Estimation and Analysis 106 3.14 Example 106 3.15 Discussion and Extensions 110 3.16 Notes 111 3.17 Summary 113 3.18 Problems 114 4. Factorial Designs 121 4.1 Randomization 123 4.2 Hypotheses and Sample Size 124 4.3 Estimation and Analysis 125 4.4 Example 1 126 4.5 Example 2 130 4.6 Notes 132 4.7 Summary 142 4.8 Problems 142 5. Multilevel Experiments 149 5.1 Randomization 151 5.2 Hypotheses and Sample Size 151 5.3 Estimation and Analysis 152 5.4 Example 154 5.5 Discussion and Extensions 162 5.6 Notes 164 5.7 Summary 165 5.8 Problems 166 6. Repeated Measures Designs 171 6.1 Randomization 172 6.2 Hypotheses and Sample Size 173 6.3 Estimation and Analysis 173 6.4 Example 176 6.5 Discussion and Extensions 179 6.6 Notes 182 6.7 Summary 184 6.8 Problems 184 7. Randomized Clinical Trials 191 7.1 Endpoints 194 7.2 Randomization 196 7.3 Hypotheses and Sample Size 197 7.4 Follow-up 198 7.5 Estimation and Analysis 198 7.6 Examples 200 7.7 Discussion and Extensions 205 7.8 Notes 214 7.9 Resources 220 7.10 Summary 220 7.11 Problems 221 8. Microarrays 231 8.1 Introduction 231 8.2 Genes, Gene Expression and Microarrays 231 8.3 Examples of microarray studies 240 8.4 Replication and sample size 242 8.5 Blocking and microarrays 244 8.6 Randomization and microarrays 246 8.7 Microarray data analysis issues 247 8.8 Data analysis example 259 8.9 Notes 262 8.10 Summary 263 8.11 Problems 263 Bibliography 207 Author Index 217 Subject Index 223