Introduction and New Drug Development Process (Naitee Ting).- Dose Finding Based on Pre-clinical Studies (David Salsburg.- Dose-finding Studies in Phase I and Estimation of Maximally Tolerated Dose (Marlene Modi) .-Dose-finding in Oncology ¿ Non-parametric Methods (Anastasia Ivanova) .- Dose Response in Oncology ¿ Parametric Methods (Mourad Tighiouart and André Rogatko) .- Dose Response - pharmacokinetic-pharmacodynamic approach (Nick Holford) .-General Considerations in Dose Response Study Designs (Naitee Ting) .- Clinical Trial Simulation ¿ a Case Study incorporating efficacy and tolerability dose response (Wayne Ewy, Peter Lockwood, and Candace Bramson) .- Analysis of Dose Response Studies ¿ Emax Model (Jim MacDougall) .- Analysis of Dose Response Studies ¿ Modeling Approaches (José Pinheiro, Frank Bretz, Michael Branson) .- Multiple Comparison Procedures in Dose Response Studies (Ajit Tamhane, Brent Logan) .-Partitioning tests in dose response studies with binary outcome (Xiang Ling, Jason Hsu and Naitee Ting) .- Analysis of Dose Response Relationship Based on Categorical Outcomes (Christy Chuang-Stein, Zhengqing Li) .- Power and Sample Size for Dose Response Studies (Mark Chang, Shein-Chung Chow).

This book emphasizes dose selection issues from a statistical point of view. It presentsstatisticalapplicationsinthedesignandanalysisofdose¿responsestudies. The importance of this subject can be found from the International Conference on Harmonization (ICH) E4 Guidance document. Establishing the dose¿response relationship is one of the most important act- ities in developing a new drug. A clinical development program for a new drug can be broadly divided into four phases ¿ namely Phases I, II, III, and IV. Phase I clinical trials are designed to study the clinical pharmacology. Information - tained from these studies will help in designing Phase II studies. Dose¿response relationshipsareusuallystudiedinPhaseII.PhaseIIIclinicaltrialsarelarge-scale, long-term studies. These studies serve to con?rm ?ndings from Phases I and II. ResultsobtainedfromPhasesI,II,andIIIclinicaltrialswouldthenbedocumented and submitted to regulatory agencies for drug approval. In the United States, - viewers from Food and Drug Administration (FDA) review these documents and make a decision to approve or to reject this New Drug Application (NDA). If the new drug is approved, then Phase IV studies can be started. Phase IV clinical trials are also known as postmarketing studies.