KLAUS HINKELMANN, PhD, is Professor Emeritus of Statistics at the Virginia Polytechnic Institute and State University Department of Statistics. A Fellow of the American Statistical Association and the American Association for the Advancement of Science, Dr. Hinkelmann has published extensively in the areas of design of experiments, statistical methods, and biometry.

• Preface xvii Contributors xxi1 Genetic Crosses Experiments 1Murari Singh, Sudhir Gupta, and Rajender Parsad1.1 Introduction, 11.2 Basic Objectives and Models, 21.3 Diallel Mating Design of Type I, 81.4 Diallel Crosses: Type II Designs, 141.5 Partial Diallel Crosses: No Blocking or Complete Blocks, 251.6 Partial Diallel Crosses in Incomplete Blocks, 321.7 Optimality, 441.8 Robustness, 591.9 Three- or Higher-Way Crosses, 611.10 Computation, 652 Design of Gene Expression Microarray Experiments 73Dan Nettleton2.1 Introduction, 732.2 Gene Expression Microarray Technology, 742.3 Preprocessing of Microarray Fluorescence Intensities, 762.4 Introduction to Gene Expression Microarray Experimental Design, 802.5 Two-Treatment Experiments Using Two-Color Microarrays, 812.6 Two-Color Microarray Experiments Involving More Than Two Treatments, 862.7 Multifactor Two-Color Microarray Experiments, 892.8 Phase 2 Designs for Complex Phase 1 Designs, 943 Spatial Analysis of Agricultural Field Experiments 109Joanne K. Stringer, Alison B. Smith, and Brian R. Cullis3.1 Introduction, 1093.2 Methods to Account for Spatial Variation, 1103.3 A Spatial Linear Mixed Model, 1163.4 Analysis of Examples, 1224 Optimal Designs for Generalized Linear Models 137John Stufken and Min Yang4.1 Introduction, 1374.2 Notation and Basic Concepts, 1414.3 Tools for Finding Locally Optimal Designs, 1454.4 GLMs with Two Parameters, 1494.5 GLMs with Multiple Parameters, 1554.6 Summary and Concluding Comments, 1615 Design and Analysis of Randomized Clinical Trials 165Janet Wittes and Zi-Fan Yu5.1 Overview, 1655.2 Components of a Randomized Clinical Trial, 1685.3 Bias, 1755.4 Statistical Analysis of Randomized Clinical Trials, 1825.5 Failure Time Studies, 1845.6 Other Topics, 2066 Monitoring Randomized Clinical Trials 213Eric S. Leifer and Nancy L. Geller6.1 Introduction, 2136.2 Normally Distributed Outcomes, 2156.3 Brownian Motion Properties, 2176.4 Brief Historical Overview of Group Sequential Methods, 2196.5 Dichotomous Outcomes, 2236.6 Time-to-Event Outcomes, 2256.7 Unconditional Power, 2276.8 Conditional Power, 2296.9 Spending Functions, 2326.10 Flexibility and Properties of Spending Functions, 2336.11 Modifying the Trial’s Sample Size Based on a Nuisance Parameter, 2356.12 Sample Size Modification Based on the Interim Treatment Effect, 2406.13 Concluding Remarks, 2467 Adaptive Randomization in Clinical Trials 251Lanju Zhang and William F. Rosenberger7.1 Introduction, 2517.2 Adaptive Randomization Procedures, 2527.3 Likelihood-Based Inference, 2647.4 Randomization-Based Inference, 2697.5 Conclusions and Practical Considerations, 2768 Search Linear Model for Identification and Discrimination 283Subir Ghosh8.1 Introduction, 2838.2 General Linear Model with Fixed Effects, 2848.3 Search Linear Model, 2858.4 Applications, 2888.5 Effects of Noise in Performance Comparison, 2939 Minimum Aberration and Related Criteria for Fractional Factorial Designs 299Hegang H. Chen and Ching-Shui Cheng9.1 Introduction, 2999.2 Projections of Fractional Factorial Designs, 3029.3 Estimation Capacity, 3049.4 Clear Two-Factor Interactions, 3079.5 Estimation Index, 3109.6 Estimation Index, Minimum Aberration, and Maximum Estimation Capacity, 3149.7 Complementary Design Theory for Minimum Aberration Designs, 3159.8 Nonregular Designs and Orthogonal Arrays, 3179.9 Generalized Minimum Aberration, 3209.10 Optimal Fractional Factorial Block Designs, 32210 Designs for Choice Experiments for the Multinomial Logit Model 331Deborah J. Street and Leonie Burgess10.1 Introduction, 33110.2 Definitions, 33210.3 The MNL Model, 33510.4 Design Comparisons, 33810.5 Optimal Designs for DCEs, 34010.6 Using Combinatorial Designs to Construct DCEs, 36410.7 Bayesian Work, 36810.8 Best–Worst Experiments, 36810.9 Miscellaneous Topics, 37011 Computer Experiments 379Max D. Morris11.1 Introduction, 37911.2 Sensitivity/Uncertainty Analysis, 38211.3 Gaussian Stochastic Process Models, 38511.4 Inference, 38911.5 Experimental Designs, 39811.6 Multivariate Output, 40311.7 Multiple Data Sources, 40611.8 Conclusion, 40912 Designs for Large-Scale Simulation Experiments, with Applications to Defense and Homeland Security 413Susan M. Sanchez, Thomas W. Lucas, Paul J. Sanchez, Christopher J. Nannini, and Hong Wan12.1 Introduction, 41312.2 Philosophy: Evolution of Computational Experiments, 41412.3 Application: U.S. Army Unmanned Aerial Vehicle (UAV) Mix Study, 42212.4 Parting Thoughts, 43713 Robust Parameter Designs 443Timothy J. Robinson and Christine M. Anderson-Cook 13.1 Introduction, 44313.2 Taguchi Signal-to-Noise Ratio Approach, 44513.3 Dual Model Response Surface Methodology, 44813.4 Single Model Response Surface Methods Using Combined Arrays, 45113.5 Computer Generated Combined Arrays, 46113.6 RPD Involving Quantitative and Qualitative Factors, 46513.7 Conclusions, 46614 Split-Plot Response Surface Designs 471G. Geoffrey Vining14.1 Introduction, 47114.2 Differences between Agricultural and Industrial Experimentation, 47214.3 OLS–GLS Equivalent Second-Order Split-Plot Designs and Analysis, 48214.4 Exact Tests for the Coeffi cients, 48814.5 Proper Residuals for Checking Assumptions, 49314.6 "Optimal" Second-Order Split-Plot Designs, 49615 Design and Analysis of Experiments for Directional Data 501Sango B. Otieno and Christine M. Anderson-Cook15.1 Summary, 50115.2 Introduction and Historical Background, 50115.3 ANOVA for Circular Data, 50915.4 ANOVA for Cylindrical Data, 52115.5 ANOVA for Spherical Data, 52415.6 Conclusions, 530References, 531Author Index 533Subject Index 545

“The presentation by Wiley is superb, as we have come to expect. All in all, this is a first class offering.”( International Statistical Review, 1 October 2012)

KLAUS HINKELMANN, PhD, is Professor Emeritus of Statistics at the Virginia Polytechnic Institute and State University Department of Statistics. A Fellow of the American Statistical Association and the American Association for the Advancement of Science, Dr. Hinkelmann has published extensively in the areas of design of experiments, statistical methods, and biometry.

• Preface xvii Contributors xxi1 Genetic Crosses Experiments 1Murari Singh, Sudhir Gupta, and Rajender Parsad1.1 Introduction, 11.2 Basic Objectives and Models, 21.3 Diallel Mating Design of Type I, 81.4 Diallel Crosses: Type II Designs, 141.5 Partial Diallel Crosses: No Blocking or Complete Blocks, 251.6 Partial Diallel Crosses in Incomplete Blocks, 321.7 Optimality, 441.8 Robustness, 591.9 Three- or Higher-Way Crosses, 611.10 Computation, 652 Design of Gene Expression Microarray Experiments 73Dan Nettleton2.1 Introduction, 732.2 Gene Expression Microarray Technology, 742.3 Preprocessing of Microarray Fluorescence Intensities, 762.4 Introduction to Gene Expression Microarray Experimental Design, 802.5 Two-Treatment Experiments Using Two-Color Microarrays, 812.6 Two-Color Microarray Experiments Involving More Than Two Treatments, 862.7 Multifactor Two-Color Microarray Experiments, 892.8 Phase 2 Designs for Complex Phase 1 Designs, 943 Spatial Analysis of Agricultural Field Experiments 109Joanne K. Stringer, Alison B. Smith, and Brian R. Cullis3.1 Introduction, 1093.2 Methods to Account for Spatial Variation, 1103.3 A Spatial Linear Mixed Model, 1163.4 Analysis of Examples, 1224 Optimal Designs for Generalized Linear Models 137John Stufken and Min Yang4.1 Introduction, 1374.2 Notation and Basic Concepts, 1414.3 Tools for Finding Locally Optimal Designs, 1454.4 GLMs with Two Parameters, 1494.5 GLMs with Multiple Parameters, 1554.6 Summary and Concluding Comments, 1615 Design and Analysis of Randomized Clinical Trials 165Janet Wittes and Zi-Fan Yu5.1 Overview, 1655.2 Components of a Randomized Clinical Trial, 1685.3 Bias, 1755.4 Statistical Analysis of Randomized Clinical Trials, 1825.5 Failure Time Studies, 1845.6 Other Topics, 2066 Monitoring Randomized Clinical Trials 213Eric S. Leifer and Nancy L. Geller6.1 Introduction, 2136.2 Normally Distributed Outcomes, 2156.3 Brownian Motion Properties, 2176.4 Brief Historical Overview of Group Sequential Methods, 2196.5 Dichotomous Outcomes, 2236.6 Time-to-Event Outcomes, 2256.7 Unconditional Power, 2276.8 Conditional Power, 2296.9 Spending Functions, 2326.10 Flexibility and Properties of Spending Functions, 2336.11 Modifying the Trial’s Sample Size Based on a Nuisance Parameter, 2356.12 Sample Size Modification Based on the Interim Treatment Effect, 2406.13 Concluding Remarks, 2467 Adaptive Randomization in Clinical Trials 251Lanju Zhang and William F. Rosenberger7.1 Introduction, 2517.2 Adaptive Randomization Procedures, 2527.3 Likelihood-Based Inference, 2647.4 Randomization-Based Inference, 2697.5 Conclusions and Practical Considerations, 2768 Search Linear Model for Identification and Discrimination 283Subir Ghosh8.1 Introduction, 2838.2 General Linear Model with Fixed Effects, 2848.3 Search Linear Model, 2858.4 Applications, 2888.5 Effects of Noise in Performance Comparison, 2939 Minimum Aberration and Related Criteria for Fractional Factorial Designs 299Hegang H. Chen and Ching-Shui Cheng9.1 Introduction, 2999.2 Projections of Fractional Factorial Designs, 3029.3 Estimation Capacity, 3049.4 Clear Two-Factor Interactions, 3079.5 Estimation Index, 3109.6 Estimation Index, Minimum Aberration, and Maximum Estimation Capacity, 3149.7 Complementary Design Theory for Minimum Aberration Designs, 3159.8 Nonregular Designs and Orthogonal Arrays, 3179.9 Generalized Minimum Aberration, 3209.10 Optimal Fractional Factorial Block Designs, 32210 Designs for Choice Experiments for the Multinomial Logit Model 331Deborah J. Street and Leonie Burgess10.1 Introduction, 33110.2 Definitions, 33210.3 The MNL Model, 33510.4 Design Comparisons, 33810.5 Optimal Designs for DCEs, 34010.6 Using Combinatorial Designs to Construct DCEs, 36410.7 Bayesian Work, 36810.8 Best–Worst Experiments, 36810.9 Miscellaneous Topics, 37011 Computer Experiments 379Max D. Morris11.1 Introduction, 37911.2 Sensitivity/Uncertainty Analysis, 38211.3 Gaussian Stochastic Process Models, 38511.4 Inference, 38911.5 Experimental Designs, 39811.6 Multivariate Output, 40311.7 Multiple Data Sources, 40611.8 Conclusion, 40912 Designs for Large-Scale Simulation Experiments, with Applications to Defense and Homeland Security 413Susan M. Sanchez, Thomas W. Lucas, Paul J. Sanchez, Christopher J. Nannini, and Hong Wan12.1 Introduction, 41312.2 Philosophy: Evolution of Computational Experiments, 41412.3 Application: U.S. Army Unmanned Aerial Vehicle (UAV) Mix Study, 42212.4 Parting Thoughts, 43713 Robust Parameter Designs 443Timothy J. Robinson and Christine M. Anderson-Cook 13.1 Introduction, 44313.2 Taguchi Signal-to-Noise Ratio Approach, 44513.3 Dual Model Response Surface Methodology, 44813.4 Single Model Response Surface Methods Using Combined Arrays, 45113.5 Computer Generated Combined Arrays, 46113.6 RPD Involving Quantitative and Qualitative Factors, 46513.7 Conclusions, 46614 Split-Plot Response Surface Designs 471G. Geoffrey Vining14.1 Introduction, 47114.2 Differences between Agricultural and Industrial Experimentation, 47214.3 OLS–GLS Equivalent Second-Order Split-Plot Designs and Analysis, 48214.4 Exact Tests for the Coeffi cients, 48814.5 Proper Residuals for Checking Assumptions, 49314.6 "Optimal" Second-Order Split-Plot Designs, 49615 Design and Analysis of Experiments for Directional Data 501Sango B. Otieno and Christine M. Anderson-Cook15.1 Summary, 50115.2 Introduction and Historical Background, 50115.3 ANOVA for Circular Data, 50915.4 ANOVA for Cylindrical Data, 52115.5 ANOVA for Spherical Data, 52415.6 Conclusions, 530References, 531Author Index 533Subject Index 545

“The presentation by Wiley is superb, as we have come to expect. All in all, this is a first class offering.”( International Statistical Review, 1 October 2012)

KLAUS HINKELMANN, PhD, is Professor Emeritus of Statistics at the Virginia Polytechnic Institute and State University Department of Statistics. A Fellow of the American Statistical Association and the American Association for the Advancement of Science, Dr. Hinkelmann has published extensively in the areas of design of experiments, statistical methods, and biometry.

• Preface xvii Contributors xxi1 Genetic Crosses Experiments 1Murari Singh, Sudhir Gupta, and Rajender Parsad1.1 Introduction, 11.2 Basic Objectives and Models, 21.3 Diallel Mating Design of Type I, 81.4 Diallel Crosses: Type II Designs, 141.5 Partial Diallel Crosses: No Blocking or Complete Blocks, 251.6 Partial Diallel Crosses in Incomplete Blocks, 321.7 Optimality, 441.8 Robustness, 591.9 Three- or Higher-Way Crosses, 611.10 Computation, 652 Design of Gene Expression Microarray Experiments 73Dan Nettleton2.1 Introduction, 732.2 Gene Expression Microarray Technology, 742.3 Preprocessing of Microarray Fluorescence Intensities, 762.4 Introduction to Gene Expression Microarray Experimental Design, 802.5 Two-Treatment Experiments Using Two-Color Microarrays, 812.6 Two-Color Microarray Experiments Involving More Than Two Treatments, 862.7 Multifactor Two-Color Microarray Experiments, 892.8 Phase 2 Designs for Complex Phase 1 Designs, 943 Spatial Analysis of Agricultural Field Experiments 109Joanne K. Stringer, Alison B. Smith, and Brian R. Cullis3.1 Introduction, 1093.2 Methods to Account for Spatial Variation, 1103.3 A Spatial Linear Mixed Model, 1163.4 Analysis of Examples, 1224 Optimal Designs for Generalized Linear Models 137John Stufken and Min Yang4.1 Introduction, 1374.2 Notation and Basic Concepts, 1414.3 Tools for Finding Locally Optimal Designs, 1454.4 GLMs with Two Parameters, 1494.5 GLMs with Multiple Parameters, 1554.6 Summary and Concluding Comments, 1615 Design and Analysis of Randomized Clinical Trials 165Janet Wittes and Zi-Fan Yu5.1 Overview, 1655.2 Components of a Randomized Clinical Trial, 1685.3 Bias, 1755.4 Statistical Analysis of Randomized Clinical Trials, 1825.5 Failure Time Studies, 1845.6 Other Topics, 2066 Monitoring Randomized Clinical Trials 213Eric S. Leifer and Nancy L. Geller6.1 Introduction, 2136.2 Normally Distributed Outcomes, 2156.3 Brownian Motion Properties, 2176.4 Brief Historical Overview of Group Sequential Methods, 2196.5 Dichotomous Outcomes, 2236.6 Time-to-Event Outcomes, 2256.7 Unconditional Power, 2276.8 Conditional Power, 2296.9 Spending Functions, 2326.10 Flexibility and Properties of Spending Functions, 2336.11 Modifying the Trial’s Sample Size Based on a Nuisance Parameter, 2356.12 Sample Size Modification Based on the Interim Treatment Effect, 2406.13 Concluding Remarks, 2467 Adaptive Randomization in Clinical Trials 251Lanju Zhang and William F. Rosenberger7.1 Introduction, 2517.2 Adaptive Randomization Procedures, 2527.3 Likelihood-Based Inference, 2647.4 Randomization-Based Inference, 2697.5 Conclusions and Practical Considerations, 2768 Search Linear Model for Identification and Discrimination 283Subir Ghosh8.1 Introduction, 2838.2 General Linear Model with Fixed Effects, 2848.3 Search Linear Model, 2858.4 Applications, 2888.5 Effects of Noise in Performance Comparison, 2939 Minimum Aberration and Related Criteria for Fractional Factorial Designs 299Hegang H. Chen and Ching-Shui Cheng9.1 Introduction, 2999.2 Projections of Fractional Factorial Designs, 3029.3 Estimation Capacity, 3049.4 Clear Two-Factor Interactions, 3079.5 Estimation Index, 3109.6 Estimation Index, Minimum Aberration, and Maximum Estimation Capacity, 3149.7 Complementary Design Theory for Minimum Aberration Designs, 3159.8 Nonregular Designs and Orthogonal Arrays, 3179.9 Generalized Minimum Aberration, 3209.10 Optimal Fractional Factorial Block Designs, 32210 Designs for Choice Experiments for the Multinomial Logit Model 331Deborah J. Street and Leonie Burgess10.1 Introduction, 33110.2 Definitions, 33210.3 The MNL Model, 33510.4 Design Comparisons, 33810.5 Optimal Designs for DCEs, 34010.6 Using Combinatorial Designs to Construct DCEs, 36410.7 Bayesian Work, 36810.8 Best–Worst Experiments, 36810.9 Miscellaneous Topics, 37011 Computer Experiments 379Max D. Morris11.1 Introduction, 37911.2 Sensitivity/Uncertainty Analysis, 38211.3 Gaussian Stochastic Process Models, 38511.4 Inference, 38911.5 Experimental Designs, 39811.6 Multivariate Output, 40311.7 Multiple Data Sources, 40611.8 Conclusion, 40912 Designs for Large-Scale Simulation Experiments, with Applications to Defense and Homeland Security 413Susan M. Sanchez, Thomas W. Lucas, Paul J. Sanchez, Christopher J. Nannini, and Hong Wan12.1 Introduction, 41312.2 Philosophy: Evolution of Computational Experiments, 41412.3 Application: U.S. Army Unmanned Aerial Vehicle (UAV) Mix Study, 42212.4 Parting Thoughts, 43713 Robust Parameter Designs 443Timothy J. Robinson and Christine M. Anderson-Cook 13.1 Introduction, 44313.2 Taguchi Signal-to-Noise Ratio Approach, 44513.3 Dual Model Response Surface Methodology, 44813.4 Single Model Response Surface Methods Using Combined Arrays, 45113.5 Computer Generated Combined Arrays, 46113.6 RPD Involving Quantitative and Qualitative Factors, 46513.7 Conclusions, 46614 Split-Plot Response Surface Designs 471G. Geoffrey Vining14.1 Introduction, 47114.2 Differences between Agricultural and Industrial Experimentation, 47214.3 OLS–GLS Equivalent Second-Order Split-Plot Designs and Analysis, 48214.4 Exact Tests for the Coeffi cients, 48814.5 Proper Residuals for Checking Assumptions, 49314.6 "Optimal" Second-Order Split-Plot Designs, 49615 Design and Analysis of Experiments for Directional Data 501Sango B. Otieno and Christine M. Anderson-Cook15.1 Summary, 50115.2 Introduction and Historical Background, 50115.3 ANOVA for Circular Data, 50915.4 ANOVA for Cylindrical Data, 52115.5 ANOVA for Spherical Data, 52415.6 Conclusions, 530References, 531Author Index 533Subject Index 545

“The presentation by Wiley is superb, as we have come to expect. All in all, this is a first class offering.”( International Statistical Review, 1 October 2012)