It addresses shortcomings in Business Process Management concerning loosely framed knowledge-intensive processes, which are characterized by their numerous valid process variants and their reliance on knowledge workers to apply their knowledge to decide on a suitable process variant that fits the context of a specific process execution. The goal was to lay the foundation for a process-aware business process management (IT-)system to support such processes. Several proof-of-concept implementations have been made for the core components and were evaluated in the domain of the healthcare. Starting from an artificial, but realistic, case about patients that arrive in the emergency room with suspected arm fractures and later progressing to a case study of the diagnosis and treatment of patients in the emergency department of a real hospital, using data from their patient files. In 2020, the PhD dissertation won the “CAiSE PhD award”, granted to outstanding PhD theses in the field of Information Systems Engineering.