Fundamentals
Introduction
Dose Finding in Clinical Trials
The Maximum Tolerated Dose
An Overview of Methodology
Bibliographic Notes
Exercises and Further Results
The Continual Reassessment Method
Introduction
One-Stage Bayesian CRM
Two-Stage CRM
Simulating CRM Trials
Practical Modifications
Bibliographic Notes
Exercises and Further Results
One-Parameter Dose–ToxicityModels
Introduction
-Equivalent Models
Model Assumptions†
Proof of Theorem 4.1†
Exercises and Further Results
Theoretical Properties
Introduction
Coherence
Large-Sample Properties
Proofs†
Exercises and Further Results
Empirical Properties
Introduction
Operating Characteristics
A Nonparametric Optimal Benchmark
Exercises and Further Results
Design Calibration
Specifications of a CRM Design
Introduction
Specifying the Clinical Parameters
A Roadmap for Choosing the Statistical Component
The Trial-and-Error Approach: Two Case Studies
Initial Guesses of Toxicity Probabilities
Introduction
Half-width () of Indifferent Interval
Calibration of 77
Case Study: The Bortezomib Trial
Exercises and Further Results
Least Informative Normal Prior
Introduction
Least Informative Prior
Calibration of 93
Optimal Least Informative Model
Revisiting the Bortezomib Trial
Initial Design
Introduction
Ordering of Dose Sequences
Building Reference Initial Designs
Practical Issues
Case Study: NeuSTART
Exercises and Further Results
CRM and Beyond
The Time-to-Event CRM
Introduction
The Basic Approach
Numerical Illustration
Enrollment Scheduling
Theoretical Properties†
Two-Stage Design
BibliographicNotes
Exercises and Further Results
CRM withMultiparameter Models
Introduction
Curve-Free Methods
Rigidity
Two-Parameter CRM†
BibliographicNotes
Exercise and Further Results
When the CRM Fails
Introduction
Trade-Off Perspective of MTD
Bivariate Dose Finding
Stochastic Approximation
Introduction
The Past Literature
The Present Relevance
The Future Challenge
Assumptions on M(x) and Y (x)†
Exercises and Further Results
References
Index
Biography
Ying Kuen Cheung
"Overall, this book comprises a detailed and very useful description of a relatively ‘novel’ and advanced method for designing dose-finding trials, which is starting to draw attention in the medical statistics community. The book focuses on the design (not analysis) of phase I and phase II dose-finding trials using the continual reassessment method (CRM) and its variants. The method is introduced alongside a description of the R package dfcrm, aiming to provide the reader with the skills to implement the method in R. ...This book aims to be a ‘how-to book’ and although it seems to require only college algebra and basic calculus concepts, I did find it very technically advanced in terms of mathematical formulations and theories. However, it was also very thorough, containing plenty of practical examples and illustrations (and corresponding implementations in R), which helps its readability. Moreover, given the complexity behind the CRM design, it is difficult to imagine how it could be presented in a simplified manner and still satisfy the need for a deep understanding of the subject."
-Rute Vieira, ISCB 2018
