. 2019 Oct;21(10):2255-2263.

doi: 10.1038/s41436-019-0484-3. Epub 2019 Mar 21.

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

Larisa H Cavallari¹, Sara L Van Driest², Cynthia A Prows³, Jeffrey R Bishop⁴, Nita A Limdi⁵, Victoria M Pratt⁶, Laura B Ramsey³, D Max Smith⁷, Sony Tuteja⁸, Benjamin Q Duong⁷, J Kevin Hicks⁹, James C Lee¹⁰, Aniwaa Owusu Obeng¹¹, Amber L Beitelshees¹², Gillian C Bell¹³, Kathryn Blake¹⁴, Daniel J Crona¹⁵, Lynn Dressler¹³, Ryan A Gregg¹⁶, Lindsay J Hines¹⁷, Stuart A Scott¹⁸, Richard C Shelton¹⁹, Kristin Wiisanen Weitzel⁷, Julie A Johnson⁷, Josh F Peterson²⁰, Philip E Empey²¹, Todd C Skaar²²; IGNITE Network

Affiliations

¹ Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA. lcavallari@cop.ufl.edu.
² Departments of Pediatrics and Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
³ Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁴ Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
⁵ Department of Neurology and Hugh Kaul Personalized Medicine Institute, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁷ Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA.
⁸ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁹ Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL, USA.
¹⁰ Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.
¹¹ Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹² Department of Medicine, University of Maryland, Baltimore, MD, USA.
¹³ Personalized Medicine Program, Mission Health, Asheville, NC, USA.
¹⁴ Center for Pharmacogenomics and Translational Research, Nemours Children's Specialty Care, Jacksonville, FL, USA.
¹⁵ Division of Pharmacotherapy and Experimental Therapeutics and Center for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC, USA.
¹⁶ OneOme, Minneapolis, MN, USA.
¹⁷ Department of Psychology, University of North Dakota, Grand Forks, ND; Sanford Brain and Spine Center and Sanford Imagenetics, Fargo, ND, USA.
¹⁸ Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY and Sema4, a Mount Sinai venture, Stamford, CT, USA.
¹⁹ Department of Psychiatry, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
²⁰ Departments of Biomedical Informatics and Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²¹ Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA.
²² Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA.

PMID: 30894703
PMCID: PMC6754805
DOI: 10.1038/s41436-019-0484-3

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

Larisa H Cavallari et al. Genet Med. 2019 Oct.

. 2019 Oct;21(10):2255-2263.

doi: 10.1038/s41436-019-0484-3. Epub 2019 Mar 21.

Authors

Affiliations

¹ Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA. lcavallari@cop.ufl.edu.
² Departments of Pediatrics and Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
³ Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁴ Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
⁵ Department of Neurology and Hugh Kaul Personalized Medicine Institute, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁷ Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA.
⁸ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁹ Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL, USA.
¹⁰ Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.
¹¹ Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹² Department of Medicine, University of Maryland, Baltimore, MD, USA.
¹³ Personalized Medicine Program, Mission Health, Asheville, NC, USA.
¹⁴ Center for Pharmacogenomics and Translational Research, Nemours Children's Specialty Care, Jacksonville, FL, USA.
¹⁵ Division of Pharmacotherapy and Experimental Therapeutics and Center for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC, USA.
¹⁶ OneOme, Minneapolis, MN, USA.
¹⁷ Department of Psychology, University of North Dakota, Grand Forks, ND; Sanford Brain and Spine Center and Sanford Imagenetics, Fargo, ND, USA.
¹⁸ Department of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai, New York, NY and Sema4, a Mount Sinai venture, Stamford, CT, USA.
¹⁹ Department of Psychiatry, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
²⁰ Departments of Biomedical Informatics and Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²¹ Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA.
²² Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA.

PMID: 30894703
PMCID: PMC6754805
DOI: 10.1038/s41436-019-0484-3

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: CYP2D6; antidepressants; implementation; opioids; pharmacogenetics.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST: None of the other authors have any conflicts of interest to declare.

Figures

**Figure 1A**
Groups enabling *CYP2D6* genotype implementation at 8 early adopters of testing. EHR, electronic health records; CTSI, Clinical Translational Science Institute

**Figure 1B**
Target drugs for *CYP2D6* genotyping among 8 early adopters. SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant *aripiprazole, haloperidol, olanzapine, perphenazine, risperidone, thioridazine, venlafaxine, atomoxetine

**Figure 2**
*CYP2D6* variations tested across sites Dup, duplications

See this image and copyright information in PMC

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

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

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