  A clinical trial is an essential step in drug development, which is often
costly and time-consuming. In silico trials are clinical trials conducted
digitally through simulation and modeling as an alternative to traditional
clinical trials. AI-enabled in silico trials can increase the case group size
by creating virtual cohorts as controls. In addition, it also enables
automation and optimization of trial design and predicts the trial success
rate. This article systematically reviews papers under three main topics:
clinical simulation, individualized predictive modeling, and computer-aided
trial design. We focus on how machine learning (ML) may be applied in these
applications. In particular, we present the machine learning problem
formulation and available data sources for each task. We end with discussing
the challenges and opportunities of AI for in silico trials in real-world
applications.
