title: Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-using genomic data to individualize treatment protocol.
abstract: OBJECTIVE
  To report the design and implementation of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR).
  
  
  METHODS
  We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR.
  
  
  RESULTS
  The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance.
  
  
  CONCLUSIONS
  This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN. Electronic address: bielinski.suzette@mayo.edu.
authors.forename: Suzette J
authors.initials: SJ
authors.lastname: Bielinski
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Olson
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Jyotishman
authors.initials: J
authors.lastname: Pathak
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN; Center for Individualized Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Weinshilboum
authors.affiliation: Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN.
authors.forename: Liewei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Lyke
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Euijung
authors.initials: E
authors.lastname: Ryu
authors.affiliation: Division of Primary Care Internal Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Targonski
authors.affiliation: Gastroenterology Department, Mayo Clinic Health System-Franciscan Healthcare, La Crosse, WI.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Van Norstrand
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Hathcock
authors.affiliation: Division of Primary Care Internal Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Paul Y
authors.initials: PY
authors.lastname: Takahashi
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN; Center for Individualized Medicine, Mayo Clinic, Rochester, MN; Division of General Internal Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: McCormick
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Kiley J
authors.initials: KJ
authors.lastname: Johnson
authors.affiliation: The Hastings Center, Garrison, NY.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Maschke
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Carolyn R
authors.initials: CR
authors.lastname: Rohrer Vitek
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Marissa S
authors.initials: MS
authors.lastname: Ellingson
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Wieben
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, MN; Division of Gastroenterology, Mayo Clinic, Rochester, MN.
authors.forename: Gianrico
authors.initials: G
authors.lastname: Farrugia
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Jody A
authors.initials: JA
authors.lastname: Morrisette
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Keri J
authors.initials: KJ
authors.lastname: Kruckeberg
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Bruflat
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Peterson
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Blommel
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Skierka
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ferber
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: John L
authors.initials: JL
authors.lastname: Black
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
authors.forename: Linnea M
authors.initials: LM
authors.lastname: Baudhuin
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Klee
authors.affiliation: Department of Information Technology, Mayo Clinic, Rochester, MN.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Ross
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Tamra L
authors.initials: TL
authors.lastname: Veldhuizen
authors.affiliation: Center for Individualized Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Cloann G
authors.initials: CG
authors.lastname: Schultz
authors.affiliation: Division of General Internal Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Caraballo
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Freimuth
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Chute
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
authors.forename: Iftikhar J
authors.initials: IJ
authors.lastname: Kullo
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy; D015331:Cohort Studies; D003657:Decision Making; D003920:Diabetes Mellitus / Q000188:drug therapy; D050171:Dyslipidemias / Q000188:drug therapy; D057286:Electronic Health Records; D005260:Female; D005820:Genetic Testing / Q000592:standards*; D060005:Genotyping Techniques; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods* / Q000592:standards; D010865:Pilot Projects; D017410:Practice Guidelines as Topic; D057285:Precision Medicine / Q000379:methods* / Q000592:standards; D011237:Predictive Value of Tests; D014481:United States
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: CAB; CAP; CDS; CGSL; CLIA; Clinical Genome Sequencing Laboratory; Clinical Laboratory Improvement Amendments; College of American Pathologists; Community Advisory Board; EMR; Electronic Medical Record and Genomics; FDA; Food and Drug Administration; NGS; PGL; PGRN; PGx; Personalized Genomics Laboratory; Pharmacogenomics Research Network; RIGHT; The Right Drug, Right Dose, Right Time—Using Genomic Data to Individualize Treatment; clinical decision support; eMERGE; electronic medical record; next-generation sequencing; pharmacogenomics