There has been enormous interest and development in Bayesian adaptive designs, especially for early phases of clinical trials. nevertheless, for phase III trials, frequentist methods still play a dominant role through controlling type I and type II errors in the hypothesis testing framework. This book providesan overview of the fundamentals of clinical trials, the key terminologies andconcepts, and a brief review and comparison on Bayesian and frequentist estimation and inference procedures. From the practical point of view, this book introduces various statistical methods that are commonly used for designing clinical trials and interim monitoring and analysis. Adaptation has a broad meaning in both Bayesian and frequentist perspectives, such as dose finding, trial early stopping for futility or superiority, dropping or adding an arm, seamlesstransitions between consecutive phases, group sequential methods, sample sizere-estimation, adaptive randomization, and subpopulation enrichment, etc. Comprehensive discussions on a variety of statistical designs, their properties, and operating characteristics for phase I, II, and III clinical trials are provided, as well as an introduction on phase IV trials. Many practical issues and challenges arising in clinical trials are addressed, and while the book mainly focuses on the Bayesian approaches for phase I and II trial designs, many important frequentist methods for phase III clinical trails are included. In addition, advanced and up-to-date topics such as jointly modeling toxicity and efficacy, seamless phase I/II trial designs, multiple testing, causal inferenceand noncompliance, adaptive randomization, issues associated with delayed outcomes, dose finding with combined drugs, and targeted therapy designs in personalized medicine development are discussed. Chapter coverage includes Fundamentals of Clinical Trials; Frequentist versus Bayesian Statistics; Phase I, II, and III Trial Designs, Adaptive Randomization, Late-onset Toxicity, Drug-combination Trials, and Targeted Therapy Design. INDICE: Preface xv 1. Introduction 1 1.1 What Are Clinical Trials? 1 1.2 Brief History and Adaptive Designs 3 1.3 Modern Clinical Trials 7 1.4 DifferentTypes of Drugs 12 1.5 New Drug Development 13 1.6 Emerging Challenges 16 1.7 Summary 17 2. Fundamentals of Clinical Trials 21 2.1 Key Components of Clinical Trials 21 2.2 Pharmacokinetics and Pharmacodynamics 35 2.3 Phases I-IV of Clinical Trials 38 2.4 Summary 42 3. Frequentist versus Bayesian Statistics 45 3.1 Basic Statistics 45 3.2 Frequentist Estimation and Inference 62 3.3 Survival Analysis 77 3.4 Bayesian Methods 86 3.5 Markov Chain Monte Carlo 105 3.6 Summary 109 4. Phase I Trial Design 113 4.1 Maximum Tolerated Dose 113 4.2 Initial Dose and Spacing 116 4.3 3 + 3 Design 120 4.4 A + B Design 125 4.5 Accelerated Titration Design 126 4.6 Biased Coin Dose-Finding Method 130 4.7 Continual Reassessment Method 132 4.8 Bayesian Model Averaging Continual Reassessment Method 140 4.9 Escalation with Overdose Control 152 4.10 Bayesian Hybrid Design Using Bayes Factor 155 4.11 Summary 162 5. Phase II Trial Design 169 5.1 Gehans Two-Stage Design 173 5.2 Simons Two-Stage Design 175 5.3 Bayesian Posterior Probability Monitoring 179 5.4 Bayesian Predictive Probability Monitoring 183 5.5 Predictive Monitoring in Randomized Phase II Trials 186 5.6 Predictive Probability with Adaptive Randomization 191 5.7 Phase II Design with Multiple Outcomes 198 5.8 Phase I/II Design with Bivariate Binary Data 206 5.9 Phase I/II Design with Times to Toxicity and Efficacy 218 5.10 Summary 229 6. Phase III Trial Design 233 6.1 Power and Sample Size 233 6.2 Comparing Means for Continuous Outcomes 240 6.3 Comparing Proportions for Binary Outcomes 252 6.4 Sample Size with Survival Data 262 6.5 Sample Size for Correlated Data 270 6.6 Group Sequential Methods 274 6.7 Adaptive Designs 297 6.8 Causality and Noncompliance310 6.9 Phase IV Post-Approval Trial 317 7. Adaptive Randomization 323 7.1 Introduction 323 7.2 Simple Randomization 326 7.3 Permuted Block Randomization 327 7.4 Stratified Randomization 328 7.5 Covariate-Adaptive Allocation by Minimization 329 7.6 Biased Coin Design 333 7.7 Play-the-Winner Rule 335 7.8 Drop-the-Loser Rule 338 7.9 Optimal Adaptive Randomization 339 7.10 Doubly Adaptive Biased Coin Design 346 7.11 Bayesian Adaptive Randomization 347 7.12 Adaptive Randomization with Efficacy and Toxicity Trade-offs 356 7.13 Fixed or AdaptiveRandomization? 360 8. Late-Onset Toxicity 367 8.1 Introduction 367 8.2 Missing Data Caused by Delayed Outcomes 369 8.3 Fractional 3 + 3 Design 371 8.4 Fractional Continual Reassessment Method 377 8.5 Time-to-Event Continual Reassessment Method 379 8.6 EM Continual Reassessment Method 382 9. Drug-Combination Trials 393 9.1 Why Are Drugs Combined? 393 9.2 New Challenges 397 9.3 SequentialDose-Finding Scheme 402 9.4 Dose Finding with Copula-Type Regression 405 9.5 Latent Contingency Table Approach 414 9.6 Combination of Discrete and Continuous Doses 419 9.7 Phase I/II Drug-Combination
- ISBN: 978-0-470-58171-1
- Editorial: John Wiley & Sons
- Encuadernacion: Cartoné
- Páginas: 384
- Fecha Publicación: 06/01/2012
- Nº Volúmenes: 1
- Idioma: Inglés