In Silico Clinical Trials: Is It Possible?

Modeling and simulation (M&S), including in silico (clinical) trials, helps accelerate drug research and development and reduce costs and have coined the term "model-informed drug development (MIDD)." Data-driven, inferential approaches are now becoming increasingly complemented by emerging complex physiologically and knowledge-based disease (and drug) models, but differ in setup, bottlenecks, data requirements, and applications (also reminiscent of the different scientific communities they arose from). At the same time, and within the MIDD landscape, regulators and drug developers start to embrace in silico trials as a potential tool to refine, reduce, and ultimately replace clinical trials. Effectively, silos between the historically distinct modeling approaches start to break down. Widespread adoption of in silico trials still needs more collaboration between different stakeholders and established precedence use cases in key applications, which is currently impeded by a shattered collection of tools and practices. In order to address these key challenges, efforts to establish best practice workflows need to be undertaken and new collaborative M&S tools devised, and an attempt to provide a coherent set of solutions is provided in this chapter. First, a dedicated workflow for in silico clinical trial (development) life cycle is provided, which takes up general ideas from the systems biology and quantitative systems pharmacology space and which implements specific steps toward regulatory qualification. Then, key characteristics of an in silico trial software platform implementation are given on the example of jinkō.ai (nova's end-to-end in silico clinical trial platform). Considering these enabling scientific and technological advances, future applications of in silico trials to refine, reduce, and replace clinical research are indicated, ranging from synthetic control strategies and digital twins, which overall shows promise to begin a new era of more efficient drug development.