Classical and adaptive clinical trial designs using ExpDesign studio

Classical and adaptive clinical trial designs using ExpDesign studio

Chang, Mark

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This book with CD-ROM introduces the Software ExpDesign Studio for classic and adaptive designs and computer simulations. The book includes step-by-step demos on creating various trial designs, using the automatic outputs to optimizethe trial design, and monitoring a clinical trial in progress. While the bookemphasizes applications over theory, key mathematic formulations are covered.In addition, ExpDesign software covers and includes SAS and R codes. This is a key reference for pharmaceutical scientists, statisticians, researchers, andothers involved in drug development. INDICE: Preface. System Requirements and Software Installation. System Requirements. Software Installation. 1. Overview of ExpDesign Studio. 1.1 How to Design a Trial with ExpDesign Studio. 1.1.1 How to Design a Classical Trial. 1.1.2 How to Design a Group Sequential Trial. 1.1.3 How to Design an Adaptive Trial. 1.1.4 How to Run Adaptive Trial Simulations. 1.1.5 How to Design a Multi-Stage Trial. 1.1.6 How to Design a Dose-Escalation Trial. 1.2 ExpDesign Menus. 2. Overview of Clinical Trial Design. 2.1 Classical Clinical Trial Designs. 2.1.1 Substantial Evidence. 2.1.1 Clinical Trial Endpoint. 2.1.2 Confirmatory Trial. 2.1.3 Exploratory Trial. 2.1.4 Multicenter Trials. 2.1.5 Trials to ShowSuperiority. 2.1.6 Trials to Show Equivalence or Non-inferiority. 2.1.7 Trials to Show Dose-response Relationship. 2.1.8 Parallel Design. 2.1.9 Crossover Design. 2.1.10 Factorial Designs. 2.2 Selection of Trial Design. 2.2.1 Balancedversus Unbalanced Designs. 2.2.2 Crossover versus Parallel Designs. 2.2.3 Dose Escalation versus Titration Designs. 2.2.4 Bioavailability versus Bioequivalence Designs. 2.2.5 Equivalence versus Bioequivalence. 2.2.6 Sample Size Determination. 2.3 Adaptive Clinical Trial Designs. 2.3.1 Group Sequential Design. 2.3.2 Sample-Size Re-Estimation Design. 2.3.3 Drop-Loser Design. 2.3.4 Response-Adaptive Randomization Design. 2.3.5 Adaptive Dose-Escalation Design. 2.3.6 Biomarker-Adaptive Design. 23.7 Multi-Stage Design of Single Arm Trials. 3. Classical Trial Design. 3.1 Overview of Classical Trial Design. 3.1.1 HypothesisTest. 3.1.2 Importance of Sample Size Calculation. 3.1.3 Factors Affecting Sample Size. 3.1.4 Avoiding Under- or Over-powered Designs. 3.2 How to CalculateSample Size with ExpDesign. 3.2.1 Test Mean Difference between Two Groups. 3.2.2 Test Proportion Difference between Two Groups. 3.2.3 Test Survival Difference between Two Groups. 3.2.4 Test Survival Difference with a Follow-up Period. 3.2.5 Exact Test for One Sample Proportion. 3.2.6 McNemar?s Test for Paired Data. 3.2.7 Non-Inferiority Test for Two Means. 3.2.8 BioEquivalence Test for Two Means. 3.2.9 BioEquivalence Test for Two Means of Log-Normal Data. 3.2.10 Equivalence Test Based on Ratio of Two Means. 3.2.11 Precision Method for MeanDifference for Paired Sample. 3.2.12 Mantel-Haenszel Test for Odds Ratio with2 Strata. 3.2.13 Pearson's Chi-square Test for Rate Difference. 3.2.14 One-Way ANOVA for Parallel Groups. 3.2.15 Dose-Response Trial for Myocardial Infarction. 3.3 Mathematic Notes on Classical Design. 3.3.1 Large Sample Size Calculation for Classical Design. 3.3.2 Commonly Used Term sand Their Mathematical Expressions. 3.3.2 Relationship between Enrollment Rate and Number of Events. 4.Group Sequential Trial Design. 4.1 Overview of Group Sequential Trial Design.4.1.1 Introduction. 4.1.2 Basics of group sequential design. 4.2 How to Design Sequential Trials with ExpDesign. 4.2.1 A design Featuring Early Efficacy Stopping for Two Means. 4.2.2 A Design Featuring Early Futility Stopping For Proportion. 4.2.3 A Design Featuring Early Stopping for Survival Endpoint. 4.2.4 A Design Featuring Early Stopping for Paired Proportions. 4.3 How to Monitor Group Sequential Trial With ExpDesign. 4.3.1 The Needs for Trial Monitoring. 4.3.2 Techniques for Monitoring a Sequential Trial. 4.3.3 How to Monitor a Trialwith ExpDesign. 4.4 Mathematical Notes on Sequential Trial Design. 4.4.1 Unified Formulation for Sequential Trial Design. 4.4.3 Calculation of Conditional Probability. 4.4.4 Conditional and Predictive Power and RCI for Trial Monitoring. 4.4.5 Bias-adjusted Estimates. 5. Adaptive Trial Design. 5.1 Overview of Adaptive Design. 5.2 Basics of Adaptive Design Methods. 5.3 How To Design Sample-Size Re-Estimation Trial With ExpDesign. 5.3.1 Sample-Size Adjustment Based on Effect Size Ratio. 5.3.2 Sample-Size Adjustment Based on Conditional Power.5.3.3 Adaptive Design for Acute Ischemic Stroke Trial. 5.3.4 Adaptive Design for Asthma Study. 5.3.5 Adaptive Design for Oncology Trial. 5.3.6 Noninferiority Design with Binary Endpoint. 5.4 How to Design Drop-Loser Trial with ExpDesign. 5.4.1 The Drop-Loser Mechanism. 5.4.2 Seamless Design of Asthma Trial. 5.5 How to Design Trial with Classifier-Biomarker. 5.5.1 Biomarker Classifications. 5.5.2 Biomarker-Adaptive Design. 5.6 How to Design Play-the-Winner Trail with ExpDesign. 5.6.1 Randomized Played-the-Winner Design. 5.6.2 Adaptive Randomization with Normal Endpoint. 6. Adaptive Trial Monitoring. 6.1 Error-Spending Approach. 6.2 How to Re-calculate Stopping Boundaries with ExpDesign. 6.3 Conditional Power and Futility Index. 6.4 How to Reestimate Sample Size with ExpDesign. 6.4.1 Calculating Conditional Power with ExpDesign. 6.4.2 ReestimatingSample Size with ExpDesign. 6.5 Trial Examples. 6.5.1 Changes in Number and Timing of the Analyses. 6.5.2 Recursive two-stage adaptive design. 6.5.3 Conditional Power and Sample-Size Reestimation. 7. Oncology Adaptive Trial Design. 7.1 Multi-Stage Trial Design. 7.1.1 Overview of Multi-Stage Design. 7.1.2 How to Design a Multi-Stage Design with ExpDesign. 7.2 Dose-Escalation Trial Design. 7.2.1 Overview of Dose-Escalation Trial. 7.2.2 Bayesian Continual Reassessment Method 126. 7.2.3 How to Design a Dose-escalation Trial with ExpDesign. 7.3Dose-Escalation Trial Monitoring With CRM. 7.4 Mathematical Notes on Multi-Stage Design. 7.4.1 Decision Tree for a Multi-stage Trial. 8.4.2 Two-Stage Design. 7.4.3 Three-Stage Design. 7.5 Mathematic Notes for CRM. 7.5.1 Probability Model for Dose-Response. 7.5.2 Prior Distribution of Parameter. 7.5.3 Likelihood Function. 7.5.4 Reassessment of Parameter. 7.5.5 Assignment of Next Patient.8. Adaptive Trial Simulator. 8.1 Adjusting Critical Region Method. 8.2 Classical Design with Two Parallel Treatment Groups. 8.3 Flexible design with SampleSize Re-estimation. 8.4 Design with Random-Play-the-Winner Randomization. 8.5Group Sequential Design with One Interim Analysis. 8.6 Design Permitting Early Stopping and Sample Size Re-estimation. 8.7 Classical Design with Multiple Treatment Groups. 8.8 Multi-Group Trial with Response-Adaptive Randomization. 8.9 Adaptive Design Featuring Dropping Losers. 8.10 Dose Response Trial Design.8.11 Dose-escalation Design for Oncology Trial. 9. Get Further Assistants from ExpDesign Studio. 9.1 ExpDesign Probability Functions. 9.2 Virtual Trial Data Generation With ExpDesign Randomizor. 9.2.1 Random Number Generation With ExpDesign. 9.2.2 How To Generate Random Univariate With ExpDesign. 9.2.3 How to Generate Random Multivariate With ExpDesign. 9.2.3 How To Generate Random MultiBinomial With ExpDesign. 9.3 ExpDesign Toolkits. 9.3.1 Graphic Calculator. 9.3.2 Probability Calculator. 9.3.3 Confidence Interval Calculator. 10. Classical Design Method Reference. 10.1 Single-Group Design. 10.1.1 One/Paired Sample Hypothesis Test for Mean. 10.1.2 One/Paired Sample Hypothesis Test for Proportion. 10.1.3 One/Paired Sample Hypothesis Test for Others. 10.1.4 Paired SampleEquivalence Test for Mean. 10.1.5 Paired Sample Equivalence Test for Proportion. 10.1.6 One Sample Confidence Interval for Mean. 10.1.7 One Sample Confidence Interval for Proportion. 10.1.8 One Sample Confidence Interval for Others. 10.2 Two-Group Design. 10.2.1 Two-Sample Hypothesis Test for Mean. 10.2.2 Two-Sample Hypothesis Test for Proportion. 10.2.3 Two-Sample Hypothesis Test for Others. 10.2.4 Two-Sample Equivalence/Non-inferiority Test for Mean. 10.2.5 Two-Sample Equivalence/Non-inferiority Test for Proportion. 10.2.6 Two-Sample Equivalence/Non-inferiority Test for Survival. 10.2.7 Two-Sample Confidence Interval for Mean. 10.2.8 Two-Sample Confidence Interval for Proportion. 10.3 Multi-Group Trial Design. 10.3.1 Multi-Sample Hypothesis Test for Mean. 10.3.2 Multi-Sample Hypothesis Test for Proportions. 10.3.3 Multi-Sample Hypothesis Test for Others. 10.3.4 Multi-Sample Confidence Interval for Others. Appendix Validation of ExpDesign Studio. A.1 Overview of Validation Process for ExpDesign Studio. A.1.1 Algorithm Validation. A.1.2 Statistical Outcome Validation. A.1.3 Criteria for Passing Validation. A.1.4 Input and GUI Validations. A.2 Validation of Classical Design Module. A.3 Validation of Group Sequential Design Module. A.3.1 Stopping Boundary and Type-I Error Rate Validation. A.3.2 Power and Sample Size Validation. A.4 Validation of Adaptive Design Module. A.4.1 Stopping Boundary and Type-I Error Rate Validation. A.4.2. Validation of Adaptive Design Monitoring. A.5 Validation of MultiStage Design Module. A.6 Validation of Traditional Dose-Escalation Design Module. A.6.1 Validation of Traditional Escalation Rule. A.6.2 Validation of Bayesian Continual Reassessment Method. A.7 Validation of Trial Simulation Module. A.8 Validation of Randomizor. A.9 Validation of ExpDesign Toolkits. A.10 Computer Programs for Validations. A.10.1 SAS Macro for the 3-stage design Validation. A.10.2 Traditional 3+3 Escalation Design Validation. A.10.3 SAS Program for CRM Validation. References. Index.

  • ISBN: 978-0-470-27612-9
  • Editorial: John Wiley & Sons
  • Encuadernacion: Cartoné
  • Páginas: 278
  • Fecha Publicación: 01/08/2008
  • Nº Volúmenes: 1
  • Idioma: Inglés