title: A prognostic model based on readily available clinical data enriched a pre-emptive pharmacogenetic testing program.
abstract: OBJECTIVE
  We describe the development, implementation, and evaluation of a model to pre-emptively select patients for genotyping based on medication exposure risk.
  
  
  METHODS
  Using deidentified electronic health records, we derived a prognostic model for the prescription of statins, warfarin, or clopidogrel. The model was implemented into a clinical decision support (CDS) tool to recommend pre-emptive genotyping for patients exceeding a prescription risk threshold. We evaluated the rule on an independent validation cohort and on an implementation cohort, representing the population in which the CDS tool was deployed.
  
  
  RESULTS
  The model exhibited moderate discrimination with area under the receiver operator characteristic curves ranging from 0.68 to 0.75 at 1 and 2 years after index dates. Risk estimates tended to underestimate true risk. The cumulative incidences of medication prescriptions at 1 and 2 years were 0.35 and 0.48, respectively, among 1,673 patients flagged by the model. The cumulative incidences in the same number of randomly sampled subjects were 0.12 and 0.19, and in patients over 50 years with the highest body mass indices, they were 0.22 and 0.34.
  
  
  CONCLUSIONS
  We demonstrate that prognostic algorithms can guide pre-emptive pharmacogenetic testing toward those likely to benefit from it.
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, 2525 West End Ave, Suite 1100, Nashville, TN 37203, USA; Department of Anesthesiology, Vanderbilt University School of Medicine, 1211 21st Avenue South, Nashville, TN 37212, USA. Electronic address: jonathan.schildcrout@vanderbilt.edu.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Schildcrout
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, 2525 West End Ave, Suite 1100, Nashville, TN 37203, USA.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Institute for Clinical and Translational Research, Vanderbilt University School of Medicine, 2525 West End Ave, Nashville, TN, 37203, USA.
authors.forename: Ioana
authors.initials: I
authors.lastname: Danciu
authors.affiliation: Institute for Clinical and Translational Research, Vanderbilt University School of Medicine, 2525 West End Ave, Nashville, TN, 37203, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Bowton
authors.affiliation: Institute for Clinical and Translational Research, Vanderbilt University School of Medicine, 2525 West End Ave, Nashville, TN, 37203, USA.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Field
authors.affiliation: Institute for Clinical and Translational Research, Vanderbilt University School of Medicine, 2525 West End Ave, Nashville, TN, 37203, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Pulley
authors.affiliation: Institute for Clinical and Translational Research, Vanderbilt University School of Medicine, 2525 West End Ave, Nashville, TN, 37203, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Basford
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 1475, Nashville, TN 37203, USA; Department of Medicine, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN 37232, USA.
authors.forename: William
authors.initials: W
authors.lastname: Gregg
authors.affiliation: Institute for Clinical and Translational Research, Vanderbilt University School of Medicine, 2525 West End Ave, Nashville, TN, 37203, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Cowan
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine, 2525 West End Ave, Suite 1100, Nashville, TN 37203, USA.
authors.forename: Frank E
authors.initials: FE
authors.lastname: Harrell
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, 1285 Medical Research Building IV, Nashville, TN 37232-0575, USA.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Roden
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 1475, Nashville, TN 37203, USA; Department of Medicine, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN 37232, USA.
authors.forename: Josh F
authors.initials: JF
authors.lastname: Peterson
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 1475, Nashville, TN 37203, USA; Department of Medicine, Vanderbilt University School of Medicine, 1161 21st Avenue South, Nashville, TN 37232, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000077144:Clopidogrel; D020000:Decision Support Systems, Clinical; D004363:Drug Utilization / Q000706:statistics & numerical data*; D057286:Electronic Health Records / Q000458:organization & administration*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010597:Pharmacogenetics / Q000458:organization & administration*; D011237:Predictive Value of Tests; D011379:Prognosis; D015397:Program Evaluation; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012307:Risk Factors; D012737:Sex Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014481:United States; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Clopidogrel; Computer decision support; Electronic health records; Precision medicine; Statin; Warfarin