TITLE: Statistical Strategies and Practical Considerations for Dose Optimization
SPEAKER: Prof. Ying Yuan, University of Texas, MD Anderson Cancer Center
MODERATOR: Jerry Li
The US Food and Drug Administration (FDA) launched Project Optimus with the aim of shifting the paradigm of dose-finding and selection towards identifying the optimal biological dose that offers the optimal balance between benefit and risk, rather than the maximum tolerated dose. However, achieving dose optimization is a challenging task that involves a variety of factors and is considerably more complicated than identifying the maximum tolerated dose, both in terms of design and implementation. This tutorial provides a comprehensive review of various design strategies for dose optimization trials, including phase I/II and II/III designs, and highlights their respective advantages and disadvantages. Additionally, practical considerations for selecting an appropriate design and planning and executing the trial are discussed. The tutorial also presents freely available software tools that can be used for designing and implementing dose optimization trials. Real-world examples are used to illustrate the approaches and their implementation.
Ying Yuan is Bettyann Asche Murray Distinguished Professor and Deputy Chair in the Department of Biostatistics at University of Texas MD Anderson Cancer Center. Dr. Yuan is an internationally renowned researcher in innovative Bayesian adaptive designs, with over 140 statistical methodology papers published on early phase trials, seamless trials, biomarker-guided trials, and basket and platform trials. The designs and software developed by Dr. Yuan’s lab (www.trialdesign.org) have been widely used in medical research institutes and pharmaceutical companies. The BOIN design, developed by Dr. Yuan’s team, is a groundbreaking oncology dose-finding design that has been recognized by the FDA as a fit-for-purpose drug development tool. Dr. Yuan was elected as the American Statistical Association Fellow, and is the leading author of two books, “Bayesian Designs for Phase I-II Clinical Trials” and “Model-Assisted Bayesian Designs for Dose Finding and Optimization,” both published by Chapman & Hall/CRC.