Preface xiv Acknowledgments xvi Part I Basic Concepts and Methods 1 1 Introduction 3 1.1 Diagnostic Test Accuracy Studies 3 1.2 Case Studies 5 1.3 Software 8 1.4 Topics Not Covered in This Book 8 2 Measures of Diagnostic Accuracy 9 2.1 Sensitivity and Specificity 9 2.2 Combined Measures of Sensitivity and Specificity 15 2.3 ROC Curve 17 2.

4 Area Under the ROC Curve 20 2.5 Sensitivity at Fixed FPR 25 2.6 Partial Area Under the ROC Curve 25 2.7 Likelihood Ratios 26 2.8 ROC Analysis When the True Diagnosis Is Not Binary 30 2.9 C-statistics and Other Measures to Compare Prediction Models 32 2.10 Detection and Localization of Multiple Lesions 33 2.11 Positive and Negative Predictive Values, Bayes'' Theorem, and Case Study 2 35 2.

12 Optimal Decision Threshold on the ROC Curve 38 2.13 Interpreting the Results of Multiple Tests 40 3 Design of Diagnostic Accuracy Studies 45 3.1 Establish the Objective of the Study 45 3.2 Identify the Target Patient Population 49 3.3 Select a Sampling Plan for Patients 50 3.4 Select the Gold Standard 56 3.5 Choose a Measure of Accuracy 61 3.6 Identify Target Reader Population 63 3.

7 Select Sampling Plan for Readers 64 3.8 Plan Data Collection 64 3.9 Plan Data Analyses 72 3.10 Determine Sample Size 77 4 Estimation and Hypothesis Testing in a Single Sample 79 4.1 Binary-scale Data 80 4.2 Ordinal-scale Data 89 4.3 Continuous-scale Data 108 4.4 Testing the Hypothesis that the ROC Curve Area or Partial Area Is a Specific Value 126 5 Comparing the Accuracy of Two Diagnostic Tests 129 5.

1 Binary-scale Data 130 5.2 Ordinal- and Continuous-scale Data 136 5.3 Tests of Equivalence 148 6 Sample Size Calculations 153 6.1 Studies Estimating the Accuracy of a Single Test 153 6.2 Sample Size for Detecting a Difference in Accuracies of Two Tests 161 6.3 Sample Size for Assessing Non-inferiority or Equivalency of Two Tests 169 6.4 Sample Size for Determining a Suitable Cutoff Value 172 6.5 Sample Size Determination for Multi-reader Studies 173 6.

6 Alternative to Sample Size Formulae 180 7 Introduction to Meta-analysis for Diagnostic Accuracy Studies 181 7.1 Objectives 182 7.2 Retrieval of the Literature 182 7.3 Inclusion/Exclusion Criteria 186 7.4 Extracting Information from the Literature 188 7.5 Statistical Analysis 190 7.6 Public Presentation 202 Part II Advanced Methods 205 8 Regression Analysis for Independent ROC Data 207 8.1 Four Clinical Studies 208 8.

2 Regression Models for Continuous-scale Tests 210 8.3 Regression Models for Ordinal-scale Tests 228 8.4 Covariate AROC Curves of Continuous-scale Tests 233 9 Analysis of Multiple Reader and/or Multiple Test Studies 235 9.1 Studies Comparing Multiple Tests with Covariates 235 9.2 Studies with Multiple Readers and Multiple Tests 245 10 Methods for Correcting Verification Bias 257 10.1 Examples 258 10.2 Impact of Verification Bias 260 10.3 A Single Binary-scale Test 261 10.

4 Correlated Binary-scale Tests 267 10.5 A Single Ordinal-scale Test 276 10.6 Correlated Ordinal-scale Tests 286 10.7 Continuous-scale Tests 296 11 Methods for Correcting Imperfect Gold Standard Bias 313 11.1 Examples 314 11.2 Impact of Imperfect Gold Standard Bias 315 11.3 One Single Binary Test in a Single Population 317 11.4 One Single Binary Test in G Populations 324 11.

5 Multiple Binary Tests in One Single Population 329 11.6 Multiple Binary Tests in G Populations 341 11.7 Multiple Ordinal-scale Tests in One Single Population 343 11.8 Multiple-scale Tests in One Single Population 347 12 Location-specific ROC Methods for Diagnostic Imaging 353 12.1 Examples 353 12.2 LROC Approach 355 12.3 FROC Approach 360 12.4 ROI Approach 377 12.

5 Comparison Between Location-specific ROC Methods 383 13 Technical Performance ("Accuracy") of Quantitative Imaging Biomarkers 385 13.1 Quantitative Imaging Biomarkers 385 13.2 Technical Performance Characteristics of a QIB 387 13.3 Precision 389 13.4 Bias and Linearity 398 13.5 Other Metrics of QIB Performance 405 13.6 Clinical Performance 407 14 Medical Test Efficacy and Effectiveness 413 14.1 General Notation 414 14.

2 Prognostic Effects 416 14.3 Predictive Effects 416 14.4 Test Strategies for Assigning Treatments 417 14.5 Explanatory Versus Pragmatic Trials of Tests 417 14.6 Explanatory Trial Designs 418 14.7 Pragmatic Trial Designs 420 14.8 Adaptive Treatment Strategy Trial Designs 423 14.9 Treatment Selection Tests 424 14.

10 Follow-on Treatment Selection Tests 425 14.11 Bibliographic Notes 428 15 Statistical Analysis for Meta-analysis 433 15.1 Binary-scale Data 433 15.2 Ordinal- or Continuous-scale Data 435 15.3 ROC Curve Area 441 15.4 Publication Bias 443 16 Risk Prediction 449 16.1 Risk Calculators 451 16.2 Calibration 454 16.

3 Discrimination 464 16.4 Appendix 16-A: Survival Analysis 469 16.5 Appendix 16-B: Survival Analysis for Competing Risks 475 16.6 Appendix 16-C: Stochastic Processes for Survival Analysis 480 16.7 Appendix 16-D: Bibliographic Notes 481 Appendix-A: Case Studies and Chapter 8 Data 485 Appendix-B: Jackknife and Bootstrap Methods of Estimating Variances and Confidence Intervals 513 Bibliography 517 Index 555.