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To register for the training courses, visit the JSM 2007 web site.

This half-day course will be taught by Christopher Coffey (University of Alabama at Birmingham), Brenda Gaydos (Eli Lilly and Company) and José Pinheiro (Novartis).

Insufficient understanding of the dose response profile of a compound is a shortcoming of clinical drug development, often leading to incorrect dose selection for the confirmatory phase. Indeed, failure to characterize adequate dosing early is often cited as a key contributor to the high late-stage attrition rate currently faced by the pharmaceutical industry. Adaptive dose-response trials allow more efficient learning about the dose response, for both efficacy and safety, earlier in development, which should ultimately reduce overall costs/timelines and provide better dosing information. Such designs may be thought of as a subset of adaptive designs in general. The rapid proliferation of adaptive designs, and inconsistent use of terminology, has created confusion about the similarities and, more importantly, the differences among the techniques. This half-day course will clarify the differences between adaptive dose-response trials and other types of adaptive designs, review traditional fixed designs and adaptive dose-response designs, and provide information on developing a Bayesian adaptive dose-response trial. Real and simulated data examples will be used to illustrate the various methods discussed in the course. The course is intended for anyone with a basic understanding of statistical methods (at approximately the 2nd year of a graduate program), basic knowledge of Bayesian methods, and some exposure to drug development concepts.

1. What are Adaptive Designs? (Definition of an 'adaptive design', classifications of adaptive designs, adaptive dose-response designs).
2. Summary of Development Stages with Emphasis on Objectives for Dose Finding (Early Exploratory Development, Late Stage Exploratory Development, Phase II, Confirmatory Development).
3. Fixed Design Dose-Response Methods (Traditional designs, Hypothesis testing approach based on multiple comparison methods, Modeling approaches, Combination approaches).
4. Adaptive Dose-Response Methods for Early Exploratory Studies (Summary of major philosophies regarding definition of maximum tolerated dose, Conventional 3+3 Designs, Model-based designs, Case-study).
5. Adaptive Dose-Response Methods for Late-Stage Exploratory Development (What can be adapted and how can information gathered during the trial be used to drive the adaptations, Hypothesis testing approach, Model-based approach, Logistical and operational issues associated with the implementation of adaptive dose-response designs).
6. Simulations to illustrate the performance and implementation of adaptive dose-response designs and their comparison to traditional methods.
7. Summary and conclusions.