title: Methodological issues in the development of a pharmacogenomic algorithm for warfarin dosing: comparison of two regression approaches.
abstract: OBJECTIVE
  To ascertain whether multiple polynomial regression (MPR) has any advantage over multiple linear regression (MLR) in developing pharmacogenomic algorithms.
  
  
  METHODS
  Two pharmacogenomic algorithms were developed based on MPR and MLR models from a warfarin pharmacogenomic data set (derivation cohort [n = 125] and validation cohort [n = 115]).
  
  
  RESULTS
  The MPR model showed better correlation with therapeutic dose (r = 0.62 vs 0.52); better diagnostic utility in distinguishing the warfarin-sensitive and warfarin-resistant patients (area under the receiver operating characteristic curves: 0.89 vs 0.81); and lower rate of underestimation (13.9 vs 20%) compared with the MLR model. Rate of overestimation was higher in the MPR than the MLR (10 vs 6.7%) model.
  
  
  CONCLUSIONS
  The MPR approach has advantages over the MLR approach in predicting accurate and safe dose.
authors.affiliation: Department of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad, 500082, India.
authors.forename: Addepalli
authors.initials: A
authors.lastname: Pavani
authors.forename: Shaik Mohammad
authors.initials: SM
authors.lastname: Naushad
authors.forename: Addepally
authors.initials: A
authors.lastname: Uma
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Kutala
mesh_terms: D000328:Adult; D000465:Algorithms; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010597:Pharmacogenetics; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D014859:Warfarin
keywords: anticoagulation; multiple linear regression; multiple polynomial regression; pharmacogenomics; warfarin