Exposure-Response Based Trial Simulations to Assess Various Adaptive Designs in Phase II Clinical Trials

Presented: Tuesday, March 25th, 2008
Speaker: Simon Zhou, Ph.D., Director of Clinical Pharmacology, Wyeth Research

View the on-demand webcast. Download instructions on how to view the web cast.

Download the webcast presentation.

Adaptive design enables clinical trials to adapt to evolving information. It is more powerful and cost effective than traditional design based on formal hypothesis in defining dose response curve and identifying optimal dose in exploratory drug development aiming to learn about pharmacology. When multiple adaptive designs are plausible, clinical trial simulation is a powerful tool to evaluate and differentiate potential outcome of individual adaptive design. It can model complicated dynamic process to evaluate key assumptions in trial design and their impacts on trial outcome. Various types of clinical trial simulations may be conducted to visualize the dynamic trial process from patient recruitment, drug distribution, treatment administration to biomarker, PK/PD and clinical responses.

Integrated with cumulative knowledge of PK/PD and biomarkers, Exposure Response (ER) based trial simulation could assess the validity and robustness of efficacy and safety findings, anticipate problems, project trial outcome. In this presentation, advantages of exposure-response based trial simulations in dosing range phase II studies will be discussed via a case study. Incorporating prior exposure variability and PK/PD information, trial simulations were conducted to (1) evaluate potential adaptive designs via traditional statistical and exposure-response analysis; (2) determine sample size and associated power in demonstrating either utility or futility; (3) define decision criteria based on multiple endpoints; (4) evaluate the robustness of efficacy and safety signals at various stages of study.