Translational approaches to treating dynamical diseases through in silico clinical trials

The primary goal of drug developers is to establish efficient and effective therapeutic protocols. Multifactorial pathologies, including dynamical diseases and complex disorders, can be difficult to treat, given the high degree of inter- and intra-patient variability and nonlinear physiological relationships. Quantitative approaches combining mechanistic disease modeling and computational strategies are increasingly leveraged to rationalize pre-clinical and clinical studies and to establish effective treatment strategies. The development of clinical trials has led to new computational methods that allow for large clinical data sets to be combined with pharmacokinetic and pharmacodynamic models of diseases. Here, we discuss recent progress using in silico clinical trials to explore treatments for a variety of complex diseases, ultimately demonstrating the immense utility of quantitative methods in drug development and medicine.