Dose finding in drug development. (Q2488571)

[The articles of this volume will not be indexed individually.] A central aspect in drug development is to establish the dose-response relationship of a candidate drug in order to find a dose range that is both efficacious and safe. In this volume the editor N. Ting and a number of distinguished coauthors make the reader familiar with the different facets of this important task. Emphasis lies on design and analysis of phase II and phase III dose-response clinical trials. An overview of the drug development process is given in chapter 1. Chapters 2 and 3 are about dose-finding in preclinical and phase I trials and deal with problems such as choosing the right doses for the first-time in human studies when only data from animal experiments are available. Chapters 4 and 5 describe special aspects of designs involving life-threatening diseases such as cancer. The following chapters deal with different facets of the design of phase II trials. Chapter 6 is about pharmacodynamics and pharmacokinetics and points out the importance of time when examining dose-response relationships. Chapter 7 presents general considerations in dose-response study designs, e.g., selection of subjects, endpoints, controls, dose range and dose spacing. How a clinical trial simulation can help to optimize designs is demonstrated in a case study in chapter 8. The analysis of dose-response trials is covered in chapters 9 to 13. The analysis of dose response studies has long been divided according to two major strategies: multiple comparison procedures and model-based approaches. The book deals with both approaches. In addition, some recent developments are presented, such as MCP-Mod, a hybrid approach to choose statistical models using multiple comparison techniques. The last chapter of the book introduces power and sample size estimation for dose-finding studies. The book is written having applications in mind. Several examples illustrate real-world problems and for some of the presented concepts SAS code is appended. Primary audience are statisticians and biostatisticians.