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This thesis sets out to test the central hypothesis that the paradigm for clinical decision support needs to shift from a technology centred paradigm to a coherent ontological-epistemological paradigm. This was achieved by formalising a coherent ontological and epistemological framework, and then applying it practically to clinical decision support. Initially the thesis reviews the need for a coherent philosophy in clinical decision support. It then goes on to describe the systematic analysis of established fundamental principles of philosophy, and the formalism of the ontological and epistemological framework. Following this the framework is applied to an analysis of clinical decision making and clinical decision support. The models derived from the analysis are then applied practically to the modelling of the management of acute renal failure patients in the intensive care setting. The results of this modelling are then combined with the decision models as the basis for the structure of a model of the decision making which controls the patient's renal replacement therapy. Finally the models representing the clinical problem and the clinical decision making process are used in the design and development of a prototype renal replacement therapy management system. The thesis concludes that a coherent ontological and epistemological framework provides clarity and insight during the analysis for and design of clinical decision support tools. The contributions of the thesis relate to the derivation and application of the framework, and the development of the renal replacement therapy management system. Thus the thesis is a foundation for future research in these two areas.