Warfarin is the most commonly used oral anticoagulant medication. Because an individual's proper warfarin dose is difficult to assess, most physicians initiate therapy at a standard dose and follow up with an INR blood test to ensure the medicine is working properly. Unfortunately, therapeutic warfarin doses vary significantly from patient to patient, so that even a standard dose can cause life-threatening hemorrhaging. Genetic and non-genetic factors both influence an individual's warfarin dose requirement and response characteristics, and although the importance of pharmacogenetics to warfarin therapy is understood, clear guidance for how such information should be applied to patient therapy is woefully absent. The Personalized Medicine Interface (PerMIT) software utility supplies this critical guidance by modeling the dose requirements and response characteristics of individual patients based on their genotypic and physical characteristics. Using state-of-the-art multivariate computations, PerMIT conveniently calculates a warfarin maintenance dose estimate and models the influence of repeated dosing on plasma drug concentration. PerMIT provides guidance during the transition from induction to maintenance therapy and limits the potential for misinterpretation of INR measurements by clearly displaying the relationship of the dosing regimen to the progress toward steady-state.
The specific aim of Phase I was to develop a computational model that estimates the most appropriate warfarin maintenance dose for an individual, accurately estimates the plasma concentration of S-warfarin following each warfarin dose, and provides a visual estimate of the time to reach steady state. PGXL Laboratories has accomplished this specific aim with the creation of the graphical patient care interface, PerMIT.
The specific aim of Phase II is to demonstrate the power of PerMIT in guiding superior clinical management of patients taking warfarin. Three technical objectives will demonstrate that the software functions as intended, that it is user friendly, and that it is clinically effective: (1) Validate the analytical accuracy of computational algorithms which drive the PerMIT module;(2) Drive design improvements through Usability Testing;(3) Measure the clinical value of PerMIT in a prospective trial of PerMIT-guided therapy versus standard of care. Completion of the above-stated objectives will: (1) confirm that the computational basis of PerMIT is consistent with the state-of-the-art in warfarin dose estimation and plasma concentration modeling, (2) assure the highest quality user interface based on a validated approach to Usability Testing, and (3) demonstrate the utility of PerMIT for improved efficiency of patient care.
Warfarin is the most commonly prescribed oral anticoagulant, but managing patients on warfarin is difficult due to variability in patients'response to the medication;indeed, adverse reactions to warfarin are second only to insulin in frequency. Inherited differences account for approximately 40% of the variability in warfarin dose response between individuals, but clinicians thus far have had no clear and easy methods or tools to help them understand and account for this variability when directing patient therapy. PerMIT:Warfarin provides muchneeded guidance to clinicians throughout the course of warfarin therapy and limits the potential for misinterpretation of blood test results (INR measurements) by clearly displaying the relationship between a patient's dosing regimen and their progress toward stable therapy.
| Borgman, Mark P; Pendleton, Robert C; McMillin, Gwendolyn A et al. (2012) Prospective pilot trial of PerMIT versus standard anticoagulation service management of patients initiating oral anticoagulation. Thromb Haemost 108:561-9 |
| Linder, Mark W; Bon Homme, Marjorie; Reynolds, Kristen K et al. (2009) Interactive modeling for ongoing utility of pharmacogenetic diagnostic testing: application for warfarin therapy. Clin Chem 55:1861-8 |
| Bon Homme, Marjorie; Reynolds, Kristen K; Valdes Jr, Roland et al. (2008) Dynamic pharmacogenetic models in anticoagulation therapy. Clin Lab Med 28:539-52 |
