The Veterans Health Administration (VHA) Clinical Pharmacogenetics Subcommittee is charged with making recommendations about whether specific pharmacogenetic tests should be used in healthcare at VHA facilities. We describe a process to inform VHA pharmacogenetic testing policy.


After developing consensus definitions of clinical validity and utility, the Subcommittee identified salient drug–gene pairs with potential clinical application in VHA. Members met monthly to discuss each drug–gene pair, the evidence of clinical utility for the associated pharmacogenetic test, and any VHA-specific testing considerations. The Subcommittee classified each test as strongly recommended, recommended, or not routinely recommended before drug initiation.


Of 30 drug–gene pair tests reviewed, the Subcommittee classified 4 (13%) as strongly recommended, including HLA-B*15:02 for carbamazepine-associated Stevens–Johnston syndrome and G6PD for rasburicase-associated hemolytic anemia; 12 (40%) as recommended, including CYP2D6 for codeine toxicity; and 14 (47%) as not routinely recommended, such as CYP2C19 for clopidogrel dosing.


Only half of drug–gene pairs with high clinical validity received Subcommittee support for policy promoting their widespread use across VHA. The Subcommittee generally found insufficient evidence of clinical utility or available, effective alternative strategies for the remainders. Continual evidence review and rigorous outcomes research will help promote the translation of pharmacogenetic discovery to healthcare.

  • Subscribe to Genetics in Medicine for full access:



Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.


  1. 1.

    Manolio TA, Chisholm RL, Ozenberger B, et al. Implementing genomic medicine in the clinic: the future is here. Genet Med . 2013;15:258–67.

  2. 2.

    Relling MV, Evans WE. Pharmacogenomics in the clinic. Nature. 2015;526:343–50.

  3. 3.

    Drew L. Pharmacogenetics: the right drug for you. Nature. 2016;537:S60–62.

  4. 4.

    United States Food and Drug Administration. Table of pharmacogenomic biomarkers in drug labels. 2017. Accessed 24 March 2018.

  5. 5.

    Van Driest SL, Shi Y, Bowton EA, et al. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clin Pharmacol Ther. 2014;95:423–31.

  6. 6.

    Scott SA. Personalizing medicine with clinical pharmacogenetics. Genet Med. 2011;13:987–95.

  7. 7.

    Patel HN, Ursan ID, Zueger PM, et al. Stakeholder views on pharmacogenomic testing. Pharmacotherapy. 2014;34:151–65.

  8. 8.

    Dunnenberger HM, Crews KR, Hoffman JM, et al. Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers. Annu Rev Pharmacol Toxicol. 2015;55:89–106.

  9. 9.

    Bielinski SJ, Olson JE, Pathak J, et al. Preemptive genotyping for personalized medicine: design of the right drug, right dose, right time-using genomic data to individualize treatment protocol. Mayo Clin Proc. 2014;89:25–33.

  10. 10.

    Rasmussen-Torvik LJ, Stallings SC, Gordon AS, et al. Design and anticipated outcomes of the eMERGE-PGx project: a multicenter pilot for preemptive pharmacogenomics in electronic health record systems. Clin Pharmacol Ther. 2014;96:482–9.

  11. 11.

    Luzum JA, Pakyz RE, Elsey AR, et al. The Pharmacogenomics Research Network Translational Pharmacogenetics Program: outcomes and metrics of pharmacogenetic implementations across diverse healthcare systems. Clin Pharmacol Ther. 2017;102:502–10.

  12. 12.

    O’Donnell PH, Danahey K, Jacobs M, et al. Adoption of a clinical pharmacogenomics implementation program during outpatient care--initial results of the University of Chicago “1200 Patients Project”. Am J Med Genet C Semin Med Genet . 2014;166c:68–75.

  13. 13.

    van der Wouden CH, Cambon-Thomsen A, Cecchin E, et al. Implementing pharmacogenomics in Europe: design and implementation strategy of the Ubiquitous Pharmacogenomics Consortium. Clin Pharmacol Ther. 2017;101:341–58.

  14. 14.

    Empey PE, Stevenson JM, Tuteja S, et al. Multi-site investigation of strategies for the implementation of CYP2C19 genotype-guided antiplatelet therapy. Clin Pharmacol Ther. 2017. Dec 26. [Epub ahead of print].

  15. 15.

    Department of Veterans Affairs. VHA handbook 1106.01: pathology and laboratory medicine service procedures. 2016. Accessed 24 March 2018.

  16. 16.

    Wang B, Canestaro WJ, Choudhry NK. Clinical evidence supporting pharmacogenomic biomarker testing provided in US Food and Drug Administration drug labels. JAMA Intern Med. 2014;174:1938–44.

  17. 17.

    Caudle KE, Klein TE, Hoffman JM, et al. Incorporation of pharmacogenomics into routine clinical practice: the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline development process. Curr Drug Metab. 2014;15:209–17.

  18. 18.

    Whirl-Carrillo M, McDonagh EM, Hebert JM, et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther . 2012;92:414–7.

  19. 19.

    Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin Pharmacol Ther. 2011;89:464–7.

  20. 20.

    Haddow J, Palomaki G. ACCE: a model process for evaluating data on emerging genetic tests. In: Khoury M, Little J, Burke W, editors. Human genome epidemiology. Oxford: Oxford University Press; 2004. p. 217–33.

  21. 21.

    Gaedigk A, Ingelman-Sundberg M, Miller NA, et al. The Pharmacogene Variation (PharmVar) Consortium: incorporation of the Human Cytochrome P450 (CYP) Allele Nomenclature Database. Clin Pharmacol Ther. 2017;103:399–401.

  22. 22.

    PharmaADME. 2017. Accessed 24 March 2018.

  23. 23.

    International SAE Consortium. 2017. Accessed 24 March 2018.

  24. 24.

    Pharmacogenetics of Membrane Transporters Database. 2015. Accessed 24 March 2018.

  25. 25.

    Martin MA, Klein TE, Dong BJ, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and abacavir dosing. Clin Pharmacol Ther. 2012;91:734–8.

  26. 26.

    Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther. 2014;95:376–82.

  27. 27.

    Scott SA, Sangkuhl K, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013;94:317–23.

  28. 28.

    Keeling NJ, Rosenthal MM, West-Strum D, et al. Preemptive pharmacogenetic testing: exploring the knowledge and perspectives of US payers. Genet Med. 2017. Oct 26. [Epub ahead of print].

  29. 29.

    Hess GP, Fonseca E, Scott R, et al. Pharmacogenomic and pharmacogenetic-guided therapy as a tool in precision medicine: current state and factors impacting acceptance by stakeholders. Genet Res. 2015;97:e13.

  30. 30.

    ACMG Board of Directors. Clinical utility of genetic and genomic services: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2015;17:505.

  31. 31.

    Drozda K, Pacanowski MA. Clinical trial designs to support clinical utility of pharmacogenomic testing. Pharmacotherapy. 2017;37:1000–4.

  32. 32.

    Snyder SR, Mitropoulou C, Patrinos GP, et al. Economic evaluation of pharmacogenomics: a value-based approach to pragmatic decision making in the face of complexity. Public Health Genomics. 2014;17:256–64.

  33. 33.

    O’Donnell PH, Wadhwa N, Danahey K, et al. Pharmacogenomics-based point-of-care clinical decision support significantly alters drug prescribing. Clin Pharmacol Ther. 2017;102:859–69.

  34. 34.

    Goldspiel BR, Flegel WA, DiPatrizio G, et al. Integrating pharmacogenetic information and clinical decision support into the electronic health record. J Am Med Inform Assoc. 2014;21:522–8.

  35. 35.

    Crews KR, Cross SJ, McCormick JN, et al. Development and implementation of a pharmacist-managed clinical pharmacogenetics service. Am J Health Syst Pharm. 2011;68:143–50.

  36. 36.

    Phillips KA, Veenstra DL, Oren E, et al. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA. 2001;286:2270–9.

  37. 37.

    Sperber NR, Carpenter JS, Cavallari LH, et al. Challenges and strategies for implementing genomic services in diverse settings: experiences from the Implementing GeNomics In pracTicE (IGNITE) network. BMC Med Genomics. 2017;10:35.

  38. 38.

    Dotson WD, Douglas MP, Kolor K, et al. Prioritizing genomic applications for action by level of evidence: a horizon-scanning method. Clin Pharmacol Ther. 2014;95:394–402.

  39. 39.

    Centers for Disease Control and Prevention Office of Public Health Genomics. Public Health Genomics Knowledge Base (v2.1): Tier TableDatabase. 2017. Accessed 24 March 2018.

  40. 40.

    Gage BF, Bass AR, 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;318:1115–24.

Download references


JLV is supported by Career Development Award IK2-CX001262 from the Clinical Sciences Research and Development (CSR&D) Service of the US Department of Veterans Affairs (VA). VMP is supported by the IGNITE project grant (U01-HG007762) from the National Institutes of Health and the Indiana University Health–Indiana University School of Medicine Strategic Research Initiative. The Pharmacogenomics Analysis Laboratory at the Central Arkansas Veterans Healthcare System is funded by the Cooperative Studies Program of the VA CSR&D Service. The contents do not necessarily represent the views of the US government or the VA.

Author information


  1. Section of General Internal Medicine, VA Boston Healthcare System, Boston, Massachusetts, USA

    • Jason L. Vassy MD, MPH
  2. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA

    • Jason L. Vassy MD, MPH
  3. Division of General Internal Medicine and Primary Care, Brigham and Women’s Hospital, Boston, Massachusetts, USA

    • Jason L. Vassy MD, MPH
  4. Pharmacogenomics Analysis Laboratory, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA

    • Annjanette Stone BS
    •  & Steven A. Schichman MD, PhD
  5. Richard L. Roudebush VA Medical Center, Indianapolis, Indiana, USA

    • John T. Callaghan MD, PhD
  6. Indiana University School of Medicine, Indianapolis, Indiana, USA

    • John T. Callaghan MD, PhD
    •  & Victoria M. Pratt PhD
  7. VA San Diego Healthcare System, San Diego, California, USA

    • Margaret Mendes PharmD
    •  & Jessica Wang-Rodriguez MD
  8. Office of Specialty Care Services, Veterans Health Administration, Washington, DC, USA

    • Laurence J. Meyer MD, PhD
  9. Office of Research & Development, US Department of Veterans Affairs, Washington, DC, USA

    • Ronald M. Przygodzki MD
  10. Division of Medical Genetics, Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California, USA

    • Maren T. Scheuner MD, MPH
  11. Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, USA

    • Maren T. Scheuner MD, MPH
  12. University of California San Diego, San Diego, California, USA

    • Jessica Wang-Rodriguez MD


  1. Search for Jason L. Vassy MD, MPH in:

  2. Search for Annjanette Stone BS in:

  3. Search for John T. Callaghan MD, PhD in:

  4. Search for Margaret Mendes PharmD in:

  5. Search for Laurence J. Meyer MD, PhD in:

  6. Search for Victoria M. Pratt PhD in:

  7. Search for Ronald M. Przygodzki MD in:

  8. Search for Maren T. Scheuner MD, MPH in:

  9. Search for Jessica Wang-Rodriguez MD in:

  10. Search for Steven A. Schichman MD, PhD in:


  1. for the VHA Clinical Pharmacogenetics Subcommittee


    The authors declare no conflicts of interest.

    Corresponding author

    Correspondence to Jason L. Vassy MD, MPH.

    Electronic supplementary material

    About this article

    Publication history





    Rights and permissions

    To obtain permission to re-use content from this article visit RightsLink.