Informatics Infrastructure for the Learning Health System.

The learning health system (LHS) paradigm focuses on generation of new knowledge based on analysis of data collected during clinical care, as well as continuous improvement of the healthcare system based on the application of that knowledge and accompanying insights. Informatics provides both the infrastructure that makes an LHS possible and the engine that drives it forward, playing a central role at each step of the LHS cycle. In this review we begin by describing the origin and foundations of the LHS. We then examine the role of informatics and data science across all aspects of the LHS cycle. We contextualize the technical aspects of the LHS through the lens of governance and culture change. Finally, we conclude with a discussion of unresolved challenges and future directions.