Dose Finding in Drug Development

1. Front Matter

   Pages I-XIV

   PDF

2. Introduction and New Drug Development Process

   • Naitee Ting

   Pages 1-17

3. Dose Finding Based on Preclinical Studies

   • David Salsburg

   Pages 18-29

4. Dose-Finding Studies in Phase I and Estimation of Maximally Tolerated Dose

   • Marlene Modi

   Pages 30-48

5. Dose-Finding in Oncology—Nonparametric Methods

   • Anastasia Ivanova

   Pages 49-58

6. Dose Finding in Oncology—Parametric Methods

   • Mourad Tighiouart, André Rogatko

   Pages 59-72

7. Dose Response: Pharmacokinetic–Pharmacodynamic Approach

   • Nick Holford

   Pages 73-88

8. General Considerations in Dose–Response Study Designs

   • Naitee Ting

   Pages 89-105

9. Clinical Trial Simulation—A Case Study Incorporating Efficacy and Tolerability Dose Response

   • Wayne Ewy, Peter Lockwood, Candace Bramson

   Pages 106-126

10. Analysis of Dose–Response Studies—Emax Model

    • James Macdougall

    Pages 127-145

11. Analysis of Dose–Response Studies—Modeling Approaches

    • José C. Pinheiro, Frank Bretz, Michael Branson

    Pages 146-171

12. Multiple Comparison Procedures in Dose Response Studies

    • Ajit C. Tamhane, Brent R. Logan

    Pages 172-183

13. Partitioning Tests in Dose–Response Studies with Binary Outcomes

    • Xiang Ling, Jason Hsu, Naitee Ting

    Pages 184-199

14. Analysis of Dose–Response Relationship Based on Categorical Outcomes

    • Christy Chuang-Stein, Zhengqing Li

    Pages 200-219

15. Power and Sample Size for Dose Response Studies

    • Mark Chang, Shein-Chung Chow

    Pages 220-241

16. Back Matter

    Pages 243-248

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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.

• Maxima
• Radiologieinformationssystem
• clinical trial
• computerassistierte Detektion
• development
• drug
• drug development
• pharmaceutical
• pharmacy
• research
• statistics

From the reviews:

"The book will be of particular interest to statisticians with some pharmaceutical industry experience who find themselves working on phase II dose finding problems. It will also be valuable for clinicians and pharmacokineticists with some statistical background. All chapters in the book are extensively referenced as they each do not pretend to exhaust their subject." Journal of Biopharmaceutical Statistics, Issue #2, 2007

"The book is a collection of chapters contributed by different authors, each addressing a different aspect of the important problem of how to identify appropriate doses of medication during the drug development process … . Consequently the most appropriate audience is statisticians and biostatisticians who desire an overview of the medical and regulatory contexts of the design and analysis of dose response studies … . On the whole the individual chapters are well written, and the book overall is a nice reference … ." (C. A. Fung, Short Book Reviews, Vol. 26 (2), 2006)

"Dose Finding in Drug Development is a contemporary roadmap to the statistical design and analysis of dose-response studies, particularly those in phases II and III of drug development. ...In general, the book is easy to read. ...At roughly $5.71 per chapters, with each chapter authored by between one and three established experts, the book is a high-yield investment of any reader's time and money." (Thomas E. Bradstreet, Journal of the American Statistical Association, Vol. 102, No. 477, 2007)

• Pfizer Global Research and Development, New London

  Naitee Ting

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