title: A Bayesian decision support tool for efficient dose individualization of warfarin in adults and children.
abstract: BACKGROUND
  Warfarin is the most widely prescribed anticoagulant for the prevention and treatment of thromboembolic events. Although highly effective, the use of warfarin is limited by a narrow therapeutic range combined with a more than ten-fold difference in the dose required for adequate anticoagulation in adults. An optimal dose that leads to a favourable balance between the wanted antithrombotic effect and the risk of bleeding as measured by the prothrombin time International Normalised Ratio (INR) must be found for each patient. A model describing the time-course of the INR response can be used to aid dose selection before starting therapy (a priori dose prediction) and after therapy has been initiated (a posteriori dose revision).
  
  
  RESULTS
  In this paper we describe a warfarin decision support tool. It was transferred from a population PKPD-model for warfarin developed in NONMEM to a platform independent tool written in Java. The tool proved capable of solving a system of differential equations that represent the pharmacokinetics and pharmacodynamics of warfarin with a performance comparable to NONMEM. To estimate an a priori dose the user enters information on body weight, age, baseline and target INR, and optionally CYP2C9 and VKORC1 genotype. By adding information about previous doses and INR observations, the tool will suggest a new dose a posteriori through Bayesian forecasting. Results are displayed as the predicted dose per day and per week, and graphically as the predicted INR curve. The tool can also be used to predict INR following any given dose regimen, e.g. a fixed or an individualized loading-dose regimen.
  
  
  CONCLUSIONS
  We believe that this type of mechanism-based decision support tool could be useful for initiating and maintaining warfarin therapy in the clinic. It will ensure more consistent dose adjustment practices between prescribers, and provide efficient and truly individualized warfarin dosing in both children and adults.
authors.affiliation: Department of Medical Sciences, Clinical Pharmacology and Science for Life Laboratory, Uppsala University, SE-751 85, Uppsala, Sweden. anna-karin.hamberg@medsci.uu.se.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Hamberg
authors.affiliation: Department of Engineering Sciences, Uppsala University, Box 256, SE-751 05, Uppsala, Sweden. jacob.hellman.88@gmail.com.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hellman
authors.affiliation: Department of Engineering Sciences, Uppsala University, Box 256, SE-751 05, Uppsala, Sweden. jonnydahlberg86@gmail.com.
authors.forename: Jonny
authors.initials: J
authors.lastname: Dahlberg
authors.affiliation: Pharmetheus AB, Dag Hammarskjölds väg 52B, SE-752 37, Uppsala, Sweden. niclas.jonsson@pharmetheus.com.
authors.forename: E Niclas
authors.initials: EN
authors.lastname: Jonsson
authors.affiliation: Department of Medical Sciences, Clinical Pharmacology and Science for Life Laboratory, Uppsala University, SE-751 85, Uppsala, Sweden. mia.wadelius@medsci.uu.se.
authors.forename: Mia
authors.initials: M
authors.lastname: Wadelius
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage*; D001499:Bayes Theorem; D002648:Child; D020000:Decision Support Systems, Clinical; D054796:Drug Dosage Calculations; D006801:Humans; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin