Abstract: This paper presents the requirements gathering and software architecture derivation approach developed by the University of Texas at Austin and leveraged by the National Cancer Institute (NCI) in their efforts to automate the creation, management, and evaluation of clinical trials. NCI must face the complexity of managing clinical trials and coordinating large numbers and varied types of stakeholders. The Systems Engineering Process Activities (SEPA) from the University of Texas at Austin is well suited to address domain modeling and software development at NCI due to a strong emphasis on explicit traceability from a derived architecture to individual Knowledge Acquisition (KA) sessions as well as facilitated resolution among conflicting stakeholder contributions. Specifically, this paper focuses on the SEPA Domain Reference Architecture (DRA), a software architecture designed to capture domain requirements (i.e., domain data, functionality, and timing).