Statistical Methods for Dose-Finding Experiments

Description

Dose-finding experiments define the safe dosage of a drug in development, in terms of the quantity given to a patient. Statistical methods play a crucial role in identifying optimal dosage. Used appropriately, these methods provide reliable results and reduce trial duration and costs. In practice, however, dose-finding is often done poorly, with widely used conventional methods frequently being unreliable, leading to inaccurate results. However, there have been many advances in recent years, with new statistical techniques being developed and it is important that these new techniques are utilized correctly. Statistical Methods for Dose-Finding Experiments reviews the main statistical approaches for dose-finding in phase I/II clinical trials and presents practical guidance on their correct use. Includes an introductory section, summarizing the essential concepts in dose-finding. Contains a section on algorithm-based approaches, such as the traditional 3+3 design, and a section on model-based approaches, such as the continual reassessment method. Explains fundamental issues, such as how to stop trials early and how to cope with delayed or ordinal outcomes. Discusses in detail the main websites and software used to implement the methods. Features numerous worked examples making use of real data. Statistical Methods for Dose-Finding Experiments is an important collaboration from the leading experts in the area. Primarily aimed at statisticians and clinicians working in clinical trials and medical research, there is also much to benefit graduate students of biostatistics.Content: Chapter 1 Basic Concepts in Dose?Finding (pages 3–18): Sylvie ChevretChapter 2 Philosophy and Methodology of Dose?Finding – a Regulatory Perspective (pages 19–57): Robert HemmingsChapter 3 Traditional and Modified Algorithm?Based Designs for Phase I Cancer Clinical Trials (pages 59–90): Weichung Joe Shih and Yong LinChapter 4 Accelerated Titration Designs (pages 91–113): Janet Dancey, Boris Freidlin and Larry RubinsteinChapter 5 Group Up?and?Down Designs in Toxicity Studies (pages 115–130): Anna Ivanova and Nancy FlournoyChapter 6 The Continual Reassessment Method (pages 131–148): Sylvie Chevret and Sarah ZoharChapter 7 Using Bayesian Decision Theory in Dose?Escalation Studies (pages 149–171): John WhiteheadChapter 8 Dose?Escalation with Overdose Control (pages 173–188): Mourad Tighiouart and Andre RogatkoChapter 9 Dose?Escalation Methods for Phase I Healthy Volunteer Studies (pages 189–203): Y. ZhouChapter 10 Defining Stopping Rules (pages 205–224): Sarah ZoharChapter 11 Dose?Finding with Delayed Binary Outcomes in Cancer Trials (pages 225–242): Ying Kuen CheungChapter 12 Dose?Finding Based on Multiple Ordinal Toxicities in Phase I Oncology Trials (pages 243–258): B. Nebiyou Bekele and Peter F. ThallChapter 13 A Two?Stage Design for Dose?Finding with Two Agents (pages 259–274): Peter F. ThallChapter 14 Using Both Efficacy and Toxicity for Dose?Finding (pages 275–285): Peter F. Thall and John D. CookChapter 15 Websites and Software (pages 287–306): Sarah Zohar