Subjects

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.

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Acknowledgements

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

Affiliations

  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

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  1. for the VHA Clinical Pharmacogenetics Subcommittee

    DISCLOSURE

    The authors declare no conflicts of interest.

    Corresponding author

    Correspondence to Jason L. Vassy MD, MPH.

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    https://doi.org/10.1038/s41436-018-0057-x

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