This talk will cover how to evaluate and optimize clinical trial designs using the Fisher Information Matrix (FIM), as implemented in tools like NONMEM's $DESIGN and PopED. While clinical trial simulation is a powerful approach for assessing design characteristics, such as model identifiability, parameter precision, and even type I error and power, FIM-based evaluation offers a faster alternative that enables exploration of many more designs and makes true design optimization feasible. A number of examples will be presented to show how design evaluation and optimization can be useful in a model-informed drug development context. Robust design techniques that account for uncertainty in models and model parameters will also be discussed.

This talk explores how model-informed drug development (MIDD) can evolve from a supportive tool into a central pillar of clinical strategy. Using the development of AZD8233—a novel PCSK9 antisense oligonucleotide—as a case study, the presentation will walk through how modeling guided key decisions from Phase 2b to Phase 3, including trial design, dose optimization, and cardiovascular risk prediction. The MIDD Webinar Series, coordinated by Yash Kapoor and Fulya Akpinar Singh, is a series of webinars focused on shaping the future of drug development and regulatory decision-making sponsored by the ISoP Education Committee. Topics range from MIDD approaches in regulatory submission to pharmacometrics topics that are at the core of model development.