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Building Evidence for Clinical Use of Pharmacogenomics and Reimbursement for Testing

      The evidence gap in outcomes with pharmacogenomic testing and testing reimbursement are major challenges to pharmacogenomic implementation.

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      References

        • Collins F.S.
        • Varmus H.
        A new initiative on precision medicine.
        N Engl J Med. 2015; 372: 793-795
        • O’Donnell P.H.
        • Wadhwa N.
        • Danahey K.
        • et al.
        Pharmacogenomics-based point-of-care clinical decision support significantly alters drug prescribing.
        Clin Pharmacol Ther. 2017; 102: 859-869
        • Hoffman J.M.
        • Haidar C.E.
        • Wilkinson M.R.
        • et al.
        PG4KDS: a model for the clinical implementation of pre-emptive pharmacogenetics.
        Am J Med Genet C Semin Med Genet. 2014; 166C: 45-55
        • Peterson J.F.
        • Field J.R.
        • Unertl K.M.
        • et al.
        Physician response to implementation of genotype-tailored antiplatelet therapy.
        Clin Pharmacol Ther. 2016; 100: 67-74
        • Pulley J.M.
        • Denny J.C.
        • Peterson J.F.
        • et al.
        Operational implementation of prospective genotyping for personalized medicine: the design of the vanderbilt PREDICT project.
        Clin Pharmacol Ther. 2012; 92: 87-95
        • Eadon M.T.
        • Desta Z.
        • Levy K.D.
        • et al.
        Implementation of a pharmacogenomics consult service to support the INGENIOUS trial.
        Clin Pharmacol Ther. 2016; 100: 63-66
        • Hicks J.K.
        • Stowe D.
        • Willner M.A.
        • et al.
        Implementation of clinical pharmacogenomics within a large health system: from electronic health record decision support to consultation services.
        Pharmacotherapy. 2016; 36: 940-948
        • Cavallari L.H.
        • Beitelshees A.L.
        • Blake K.V.
        • et al.
        The IGNITE pharmacogenetics working group: an opportunity for building evidence with pharmacogenetic implementation in a real-world setting.
        Clin Transl Sci. 2017; 10: 143-146
        • Deiman B.A.
        • Tonino P.A.
        • Kouhestani K.
        • et al.
        Reduced number of cardiovascular events and increased cost-effectiveness by genotype-guided antiplatelet therapy in patients undergoing percutaneous coronary interventions in the Netherlands.
        Neth Heart J. 2016; 24: 589-599
        • Sanchez-Ramos J.
        • Davila-Fajardo C.L.
        • Toledo Frias P.
        • et al.
        Results of genotype-guided antiplatelet therapy in patients who undergone percutaneous coronary intervention with stent.
        Int J Cardiol. 2016; 225: 289-295
        • van der Wouden C.H.
        • Cambon-Thomsen A.
        • Cecchin E.
        • et al.
        Implementing pharmacogenomics in Europe: design and implementation strategy of the ubiquitous pharmacogenomics consortium.
        Clin Pharmacol Ther. 2017; 101: 341-358
        • Relling M.V.
        • Klein T.E.
        CPIC: clinical pharmacogenetics implementation consortium of the pharmacogenomics research network.
        Clin Pharmacol Ther. 2011; 89: 464-467
        • Swen J.J.
        • Nijenhuis M.
        • de Boer A.
        • et al.
        Pharmacogenetics: from bench to byte--an update of guidelines.
        Clin Pharmacol Ther. 2011; 89: 662-673
        • Relling M.V.
        • Altman R.B.
        • Goetz M.P.
        • et al.
        Clinical implementation of pharmacogenomics: overcoming genetic exceptionalism.
        Lancet Oncol. 2010; 11: 507-509
        • Khoury M.J.
        Dealing with the evidence dilemma in genomics and personalized medicine.
        Clin Pharmacol Ther. 2010; 87: 635-638
        • van der Wouden C.H.
        • Swen J.J.
        • Samwald M.
        • et al.
        A brighter future for the implementation of pharmacogenomic testing.
        Eur J Hum Genet. 2016; 24: 1658-1660
        • Mallal S.
        • Phillips E.
        • Carosi G.
        • et al.
        HLA-B∗5701 screening for hypersensitivity to abacavir.
        N Engl J Med. 2008; 358: 568-579
      1. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Department of Health and Human Services. Panel on antiretroviral guidelines for adults and adolescents. Available at: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed February 28, 2018.

        • Relling M.V.
        • Gardner E.E.
        • Sandborn W.J.
        • et al.
        Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing.
        Clin Pharmacol Ther. 2011; 89: 387-391
        • Coenen M.J.
        • de Jong D.J.
        • van Marrewijk C.J.
        • et al.
        Identification of patients with variants in TPMT and dose reduction reduces hematologic events during thiopurine treatment of inflammatory bowel disease.
        Gastroenterology. 2015; 149: 907-917.e7
        • Weitzel K.W.
        • Smith D.M.
        • Elsey A.R.
        • et al.
        Implementation of standardized clinical processes for TPMT testing in a diverse multidisciplinary population: challenges and lessons learned.
        Clin Transl Sci. 2018; 11: 175-181
        • Kimmel S.E.
        • French B.
        • Kasner S.E.
        • et al.
        A pharmacogenetic versus a clinical algorithm for warfarin dosing.
        N Engl J Med. 2013; 369: 2283-2293
        • Pirmohamed M.
        • Burnside G.
        • Eriksson N.
        • et al.
        A randomized trial of genotype-guided dosing of warfarin.
        N Engl J Med. 2013; 369: 2294-2303
        • Gage B.F.
        • Bass A.R.
        • Lin H.
        • et al.
        Effect of genotype-guided warfarin dosing on clinical events and anticoagulation control among patients undergoing hip or knee arthroplasty: the GIFT randomized clinical trial.
        JAMA. 2017; 318: 1115-1124
        • Drozda K.
        • Wong S.
        • Patel S.R.
        • et al.
        Poor warfarin dose prediction with pharmacogenetic algorithms that exclude genotypes important for African Americans.
        Pharmacogenet Genomics. 2015; 25: 73-81
        • Cavallari L.H.
        Time to revisit warfarin pharmacogenetics.
        Future Cardiol. 2017; 13: 511-513
        • Johnson J.A.
        • Cavallari L.H.
        Warfarin pharmacogenetics.
        Trends Cardiovasc Med. 2015; 25: 33-41
        • Johnson J.A.
        • Gong L.
        • Whirl-Carrillo M.
        • et al.
        Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing.
        Clin Pharmacol Ther. 2011; 90: 625-629
        • Johnson J.A.
        • Caudle K.E.
        • Gong L.
        • et al.
        Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for pharmacogenetics-guided warfarin dosing: 2017 update.
        Clin Pharmacol Ther. 2017; 102: 397-404
        • Nutescu E.A.
        • Drozda K.
        • Bress A.P.
        • et al.
        Feasibility of implementing a comprehensive warfarin pharmacogenetics service.
        Pharmacotherapy. 2013; 33: 1156-1164
        • Chen P.
        • Lin J.J.
        • Lu C.S.
        • et al.
        Carbamazepine-induced toxic effects and HLA-B∗1502 screening in Taiwan.
        N Engl J Med. 2011; 364: 1126-1133
        • Ko T.M.
        • Tsai C.Y.
        • Chen S.Y.
        • et al.
        Use of HLA-B∗58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study.
        BMJ. 2015; 351: h4848
        • Phillips E.J.
        • Sukasem C.
        • Whirl-Carrillo M.
        • et al.
        Clinical pharmacogenetics implementation consortium guideline for HLA genotype and use of carbamazepine and oxcarbazepine: 2017 update.
        Clin Pharmacol Ther. 2018; 103: 574-581
        • Saito Y.
        • Stamp L.K.
        • Caudle K.E.
        • et al.
        • Clinical Pharmacogenetics Implementation Consortium
        Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for human leukocyte antigen B (HLA-B) genotype and allopurinol dosing: 2015 update.
        Clin Pharmacol Ther. 2016; 99: 36-37
        • Amstutz U.
        • Shear N.H.
        • Rieder M.J.
        • et al.
        • CPNDS clinical recommendation group
        Recommendations for HLA-B∗15:02 and HLA-A∗31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.
        Epilepsia. 2014; 55: 496-506
        • Ginsburg G.
        Medical genomics: gather and use genetic data in health care.
        Nature. 2014; 508: 451-453
        • Rosenthal G.E.
        The role of pragmatic clinical trials in the evolution of learning health systems.
        Trans Am Clin Climatol Assoc. 2014; 125 ([discussion: 17–8]): 204-216
        • Patsopoulos N.A.
        A pragmatic view on pragmatic trials.
        Dialogues Clin Neurosci. 2011; 13: 217-224
        • Terry S.F.
        An evidence framework for genetic testing.
        Genet Test Mol Biomarkers. 2017; 21: 407-408
        • Mega J.L.
        • Close S.L.
        • Wiviott S.D.
        • et al.
        Cytochrome p-450 polymorphisms and response to clopidogrel.
        N Engl J Med. 2009; 360: 354-362
        • Scott S.A.
        • Sangkuhl K.
        • Stein C.M.
        • et al.
        Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.
        Clin Pharmacol Ther. 2013; 94: 317-323
        • Sorich M.J.
        • Rowland A.
        • McKinnon R.A.
        • et al.
        CYP2C19 genotype has a greater effect on adverse cardiovascular outcomes following percutaneous coronary intervention and in Asian populations treated with clopidogrel: a meta-analysis.
        Circ Cardiovasc Genet. 2014; 7: 895-902
        • Mega J.L.
        • Simon T.
        • Collet J.P.
        • et al.
        Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis.
        JAMA. 2010; 304: 1821-1830
        • Bergmeijer T.O.
        • Janssen P.W.
        • Schipper J.C.
        • et al.
        CYP2C19 genotype-guided antiplatelet therapy in ST-segment elevation myocardial infarction patients-Rationale and design of the Patient Outcome after primary PCI (POPular) Genetics study.
        Am Heart J. 2014; 168: 16-22 e1
        • Empey P.E.
        • Stevenson J.M.
        • Tuteja S.
        • et al.
        • IGNITE Network
        Multisite investigation of strategies for the implementation of CYP2C19 genotype-guided antiplatelet therapy.
        Clin Pharmacol Ther. 2018; 104: 664-674
        • Weitzel K.W.
        • Alexander M.
        • Bernhardt B.A.
        • et al.
        The IGNITE network: a model for genomic medicine implementation and research.
        BMC Med Genomics. 2016; 9: 1
        • Cavallari L.H.
        • Lee C.R.
        • Beitelshees A.L.
        • et al.
        • IGNITE Network
        Multisite investigation of outcomes with implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention.
        JACC Cardiovasc Interv. 2018; 11: 181-191
        • Hicks J.K.
        • Bishop J.R.
        • Sangkuhl K.
        • et al.
        • Clinical Pharmacogenetics Implementation Consortium
        Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors.
        Clin Pharmacol Ther. 2015; 98: 127-134
        • Hicks J.K.
        • Sangkuhl K.
        • Swen J.J.
        • et al.
        Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update.
        Clin Pharmacol Ther. 2016; 102: 37-44
        • Bradley P.
        • Shiekh M.
        • Mehra V.
        • et al.
        Improved efficacy with targeted pharmacogenetic-guided treatment of patients with depression and anxiety: a randomized clinical trial demonstrating clinical utility.
        J Psychiatr Res. 2018; 96: 100-107
        • Brennan F.X.
        • Gardner K.R.
        • Lombard J.
        • et al.
        A naturalistic study of the effectiveness of pharmacogenetic testing to guide treatment in psychiatric patients with mood and anxiety disorders.
        Prim Care Companion CNS Disord. 2015; 17
        • Perez V.
        • Salavert A.
        • Espadaler J.
        • et al.
        Efficacy of prospective pharmacogenetic testing in the treatment of major depressive disorder: results of a randomized, double-blind clinical trial.
        BMC Psychiatry. 2017; 17: 250
        • Van Driest S.L.
        • Shi Y.
        • Bowton E.A.
        • et al.
        Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing.
        Clin Pharmacol Ther. 2014; 95: 423-431
        • Ji Y.
        • Skierka J.M.
        • Blommel J.H.
        • et al.
        Preemptive pharmacogenomic testing for precision medicine: a comprehensive analysis of five actionable pharmacogenomic genes using next-generation DNA sequencing and a customized CYP2D6 genotyping cascade.
        J Mol Diagn. 2016; 18: 438-445
      2. CPT Code Application. American Medical Association. Available at: https://www.ama-assn.org/practice-management/applying-cpt-codes. Accessed February 25, 2018.

      3. NHE Fact Sheet. Center for medicare & medicaid services. Available at: https://www.cms.gov/research-statistics-data-and-systems/statistics-trends-and-reports/nationalhealthexpenddata/nhe-fact-sheet.html. Accessed February 25, 2018.

      4. Medicare Coverage Database. Center for medicare & medicaid services. Available at: https://www.cms.gov/medicare-coverage-database. Accessed February 25, 2018.

        • Keeling N.J.
        • Rosenthal M.M.
        • West-Strum D.
        • et al.
        Preemptive pharmacogenetic testing: exploring the knowledge and perspectives of US payers.
        Genet Med. 2019; 21: 1224-1232
        • Rosenman M.B.
        • Decker B.
        • Levy K.D.
        • et al.
        Lessons learned when introducing pharmacogenomic panel testing into clinical practice.
        Value Health. 2017; 20: 54-59
        • Thervet E.
        • Loriot M.A.
        • Barbier S.
        • et al.
        Optimization of initial tacrolimus dose using pharmacogenetic testing.
        Clin Pharmacol Ther. 2010; 87: 721-726