Bridging the Gap Between Preclinical and Clinical Evaluation of Therapeutic Candidates

Session 2

Innovative Dose-Ranging Designs in “Learn”: Three Case Studies

Michael Krams, M.D.
Wyeth Pharmaceuticals

Choosing the correct dose(s) to take into confirmatory trials is a key challenge within “Learn”. We will look at three case studies within the bigger context of the overall clinical development plan. What is the most efficient process to “Learn” and “Confirm”? In “Learn” we propose to apply model-based adaptive dose-ranging designs to the initial exploration on whether we have proof-of-concept, and if yes, which doses to take forward into a confirmatory development program. Within “Confirm” we propose to consider seamless adaptive phase II/III designs to further establish appropriate understanding of the correct dose(s) in an efficient manner. Translational medicine becomes an integrator of “Learn” and “Confirm”, by enabling to link study results through the development and validation of appropriate biomarkers and endpoints. The concept of Modeling&Simulation driven drug development is key to this. We will also describe the organizational changes that had to occur to successfully implement a radically different approach in thinking about drug development in a large R&D organization.

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