With the successful completion of the Human Genome Project, the field of biotechnology has seen an exponential growth, and the rate of discovery in the -omics disciplines has far outpaced the application of these discoveries in medicine. Although research in basic biological sciences is often motivated by the potential application in medicine, there are fundamental differences in the priorities, goals, and methods between basic research, clinical research, clinical practice, and policy. However, the divergence is merely a symptom of a greater underlying problem—the inefficient flow of data, information, and knowledge between these different disciplines—a problem in informatics. This dissertation work examined the problem of translation of data, information, and knowledge from basic sciences to clinical research and clinical practice for adverse drug events, an area of active research within the clinical research enterprise. Several informatics frameworks exist for the generation and evaluation of evidence for clinical- and cost-effectiveness; however, various shortcomings have been identified in each of these frameworks, and no single framework addresses the discovery, representation, and delivery of such evidence at the point of care. As part of the dissertation, a translational informatics framework was developed for pharmacologic decision support, which addresses some of the shortcomings of other frameworks. The framework supports inquiry, discovery of new knowledge, and also representation and delivery of knowledge at the point of care. Metadata and vocabulary-based data integration methods are the foundation that support inquiry and discovery, vocabularies and controlled medical terminologies are used to represent knowledge, and such knowledge is delivered at the point of care using computerized decision support systems. Clinically relevant examples were provided for instantiation of the framework, and one specific instance that involved the development of physiological and pharmacological models to predict adverse events in anticoagulation therapy was used to examine the framework in greater detail. Framework instantiation led to the development of a physiological and pharmacological predictive model for adverse drug events in anticoagulation therapy, and the findings are generalizable to other combinations of drugs and clinical end-points.
|Advisor:||Mitchell, Joyce A.|
|Commitee:||Bray, Bruce E., Horn, Susan D., Hurdle, John F., Munger, Mark A.|
|School:||The University of Utah|
|School Location:||United States -- Utah|
|Source:||DAI-B 73/08(E), Dissertation Abstracts International|
|Subjects:||Information Technology, Medicine, Bioinformatics|
|Keywords:||Decision support, Metadata, Translational informatics, Vocabularies|
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