In this episode, we provide a comprehensive overview of digital twin technology in clinical trial design, highlighting its growing adoption for creating virtual patient populations to enhance and potentially replace traditional control groups. We describe the market's rapid expansion and the technological advancements driving this growth, such as physics-informed machine learning and quantitative systems pharmacology. We also discuss the evolving regulatory landscape, with the European Medicines Agency (EMA) leading in formal qualification of these methods, while acknowledging significant technical challenges like data quality and integration, computational complexity, and model validation. Finally, we address crucial ethical considerations surrounding informed consent and placebo use, alongside the barriers to widespread adoption and future opportunities for this transformative technology. Produced by Dr. Jake Chen.