PGXL Laboratories has access to a unique computational tool that can significantly reduce the morbidity and mortality associated with warfarin anticoagulation therapy. This project will yield a web-based software tool that will, for the first time, allow physicians to incorporate their patients' genetic and physical characteristics into individualized treatment plans. The long-term objective of this proposal is to create a software interface which generates customizable treatment plans for individual patients based on their genotypic and physical traits. Within the scope of this Phase I application, the applicants propose the development of a software tool for use with individuals undergoing warfarin therapy. The project goal is to develop a novel computational model that: (1) accurately estimates the plasma warfarin concentration following every warfarin dose while (2) providing a visual representation of the time required to achieve steady state; and (3) accurately predicts the most appropriate warfarin maintenance dose. Completion of these aims will establish that the model can provide clinicians with the three crucial elements of information they need to develop the most effective treatment strategy for each individual patient. Patient genotypes at two loci, CYP2C9 and VKORC1, will be utilized, as variants of these genes are closely associated with the reduced effectiveness of warfarin. Physical characteristics, including age, gender and weight, will also be incorporated, as well as steady-state plasma warfarin concentrations and prothrombin time, to "train" the software through a series of regression analyses. Once the software has been satisfactorily trained, Phase II of the project will take the software live, incorporating data from patients as they begin warfarin therapy. As cooperating physicians follow their patients, the model will be tested to determine how closely it predicts real-world results. At the same time, the software package will be under development to turn it into a Windows-based, user-friendly interface. The costs involved in the current methods of warfarin therapy management are great, including frequent office visits, testing, dosing adjustments and hospital stays as the result of adverse drug reactions. The greatest costs of all are the risks involved inappropriate dosing. By incorporating genetic testing into standard warfarin therapy practices, almost 100,000 people could be saved from bleeding or stroke events annually and as much as $2 billion a year could be saved. . Personalized medicine is a new approach, by which the genetic and physical characteristics of a patient are combined to produce an individualized treatment plan. Simple tools which allow physicians to easily practice personalized medicine hold great promise for the future of safe, effective and efficient patient therapy. Proposed here is a software interface which will generate a unique, customizable and dynamic model which not only will predict the optimal dose of warfarin required by a given patient, but will also guide the physician throughout the patient's course of therapy. [unreadable] [unreadable] [unreadable]