title: Validation of the acenocoumarol EU-PACT algorithms: similar performance in the Rotterdam Study cohort as in the original study.
abstract: OBJECTIVE
  To evaluate the performance of the European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) acenocoumarol dose algorithms in an independent data set. The EU-PACT trial investigates the added value of pretreatment genotyping for use of warfarin, phenprocoumon and acenocoumarol.
  
  
  METHODS
  External validation was performed in the Rotterdam Study cohort using information about 707 acenocoumarol users. R(2), which measures the strength of correlation between the predicted and observed acenocoumarol dose, mean absolute error and mean squared error were calculated to evaluate the performance of the original algorithm.
  
  
  RESULTS
  Validation resulted in a R(2) of 52.7 and 12.9% compared with an R(2) of 52.6 and 17.8% in the original study for the genotype-guided and nongenotype-guided dose algorithm, respectively. For the genotype-guided dose algorithm, the mean absolute error was 0.48 mg/day and the mean squared error was 0.38 (mg/day)(2). For the nongenotype-guided dose algorithm, the mean absolute error was 0.62 mg/day and the mean squared error was 0.63 (mg/day)(2).
  
  
  CONCLUSIONS
  The EU-PACT acenocoumarol algorithm performs just as accurately in this study as in the original study, which implies applicability in various populations.
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Rianne M F
authors.initials: RM
authors.lastname: van Schie
authors.forename: Nadia
authors.initials: N
authors.lastname: el Khedr
authors.forename: Talitha I
authors.initials: TI
authors.lastname: Verhoef
authors.forename: Martina
authors.initials: M
authors.lastname: Teichert
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Peter N
authors.initials: PN
authors.lastname: Buhre
authors.forename: Judith A M
authors.initials: JA
authors.lastname: Wessels
authors.forename: Tom
authors.initials: T
authors.lastname: Schalekamp
authors.forename: Saskia
authors.initials: S
authors.lastname: le Cessie
authors.forename: Felix J M
authors.initials: FJ
authors.lastname: van der Meer
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.forename: Anke-Hilse
authors.initials: AH
authors.lastname: Maitland-van der Zee
authors.forename: Loes E
authors.initials: LE
authors.lastname: Visser
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics; D010644:Phenprocoumon / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D064417:Vitamin K Epoxide Reductases; D000074:Acenocoumarol; D010644:Phenprocoumon