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Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing



A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers.


We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Data were collected on testing approaches, return of results procedures, applications of genotype results, challenges faced, and lessons learned.


Among early adopters, CYP2D6 testing was most commonly ordered to assist with opioid and antidepressant prescribing. Key differences among programs included test ordering and genotyping approaches, result reporting, and clinical decision support. However, all sites tested for copy-number variation and nine common variants, and reported results in the medical record. Most sites provided automatic consultation and had designated personnel to assist with genotype-informed therapy recommendations. Primary challenges were related to stakeholder support, CYP2D6 gene complexity, phenotype assignment, and sustainability.


There are specific challenges unique to CYP2D6 testing given the complexity of the gene and its relevance to multiple medications. Consensus lessons learned may guide those interested in pursuing similar clinical pharmacogenetic programs.

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This work was supported by the National Institutes of Health (NIH) IGNITE Network ( through grants U01HG007269, U01HG007253, U01HG007762, U01HG007775, and U01HG007278. Additional funding provided by the University of Florida and its Clinical Translational Science Institute (NCATS UL1TR000064 and UL1TR001427) for J.A.J., L.H.C., and K.W.W.; NHLBI R0HL092173 and K24HL133373, NCATS UL1TR000165, University of Alabama Birmingham’s Health Service Foundations' General Endowment Fund and Hugh Kaul Personalized Medicine Institute to N.A.L.; NIH Common Fund Program in Health Economics and NHLBI U01HL122904 to J.F.P.; Indiana University Health–Indiana University School of Medicine Strategic Research Initiative to V.M.P. and T.C.S.; NHGRI eMERGE Network U01HG8666 and U01HG006828 (Cincinnati Children’s Hospital Medical Center) and CIDR U01HG004438; University of Minnesota Enhance Comprehensive Pharmacist Services to Improve Patient Health Clinical Research Award to J.R.B.; NCI P30CA076292, Cancer Epidemiology Innovation Funds, DeBartolo Family Personalized Medicine Institute Pilot Research Award in Personalized Medicine, ASHP Research and Education Foundation, and OneOme to J.K.H.; NHGRI U01HG008672 and NCATS UL1TR002243; University of Pennsylvania, Center for Precision Medicine Accelerator Fund to S.T.; NCATS UL1TR001857, an Anonymous Donor, internal funds from the University of Pittsburgh Medical Center, and the Institute for Precision Medicine to P.E.E.; NCBiotech Presidential Grant to GCB; philanthropic donation by T. Denny Sanford IMAGENETICS (Internal Medicine and Genetics) to L.J.H., and NHGRI 3U01HG008701 to A.O.O.

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Correspondence to Larisa H. Cavallari PharmD.

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N.A.L. serves as a consultant for Admera Health. V.M.P. is affiliated with the Indiana University School of Medicine Pharmacogenomics Laboratory, which is a fee-for-service clinical laboratory. J.K.H. receives clinical trial support from OneOme and serves as a consultant for Quest Diagnostics. R.A.G. is employed by OneOme, a for-profit genotyping laboratory. L.H.C. has received research funding from Mallinckrodt Pharmaceuticals. The other authors declare no conflicts of interest.

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  • pharmacogenetics
  • implementation
  • CYP2D6
  • opioids
  • antidepressants

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Fig. 1: Stakeholder involvement and CYP2D6 genotyping applications.
Fig. 2