Clinical trial protocols include schedule of clinical trial activities such as clinical tests, procedures, and medications. The schedule specifies temporal constraints on the sequence of these activities, on their start times and duration, and on their potential repetitions. There is an enormous requirement to conform to the constraints found in the protocols during the conduct of the clinical trials. In this paper, we present our approach to formally represent temporal constraints found in clinical trials, and to facilitate reasoning with the constraints. We have identified a representative set of temporal constraints found in clinical trials in the immune tolerance area, and have developed a temporal constraint ontology that allows us to formulate the temporal constraints to the extent required to support clinical trials management. We use the ontology to specify temporal annotation on clinical activities in an encoded clinical trial protocol. We have developed a temporal model to encapsulate time-stamped data, and to facilitate interval-based temporal operations on the data. Using semantic web technologies, we are building a knowledge-based framework that integrates the temporal constraint ontology with the temporal model to support queries on clinical trial data. Using our approach, we can formally specify temporal constraints, and reason with the temporal knowledge to support management of clinical trials.
