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


Journal

Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831

Informations de publication

Date de publication:
10 2019
Historique:
received: 27 11 2018
accepted: 27 02 2019
pubmed: 22 3 2019
medline: 18 3 2020
entrez: 22 3 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30894703
doi: 10.1038/s41436-019-0484-3
pii: S1098-3600(21)04488-9
pmc: PMC6754805
mid: NIHMS1525471
doi:

Substances chimiques

Cytochrome P-450 CYP2D6 EC 1.14.14.1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2255-2263

Subventions

Organisme : NHGRI NIH HHS
ID : U01 HG007269
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG004438
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000165
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM131812
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001427
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008666
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL092173
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG010245
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007762
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008701
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR003096
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007253
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000064
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001857
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL122904
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008672
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL133373
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007775
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG006828
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA076292
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG007278
Pays : United States

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Auteurs

Larisa H Cavallari (LH)

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA. lcavallari@cop.ufl.edu.

Sara L Van Driest (SL)

Departments of Pediatrics and Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Cynthia A Prows (CA)

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Jeffrey R Bishop (JR)

Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.

Nita A Limdi (NA)

Department of Neurology and Hugh Kaul Personalized Medicine Institute, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Victoria M Pratt (VM)

Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.

Laura B Ramsey (LB)

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

D Max Smith (DM)

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA.

Sony Tuteja (S)

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Benjamin Q Duong (BQ)

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA.

J Kevin Hicks (JK)

Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL, USA.

James C Lee (JC)

Department of Pharmacy Practice, University of Illinois at Chicago, Chicago, IL, USA.

Aniwaa Owusu Obeng (AO)

Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Amber L Beitelshees (AL)

Department of Medicine, University of Maryland, Baltimore, MD, USA.

Gillian C Bell (GC)

Personalized Medicine Program, Mission Health, Asheville, NC, USA.

Kathryn Blake (K)

Center for Pharmacogenomics and Translational Research, Nemours Children's Specialty Care, Jacksonville, FL, USA.

Daniel J Crona (DJ)

Division of Pharmacotherapy and Experimental Therapeutics and Center for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, NC, USA.

Lynn Dressler (L)

Personalized Medicine Program, Mission Health, Asheville, NC, USA.

Ryan A Gregg (RA)

OneOme, Minneapolis, MN, USA.

Lindsay J Hines (LJ)

Department of Psychology, University of North Dakota, Grand Forks, ND; Sanford Brain and Spine Center and Sanford Imagenetics, Fargo, ND, USA.

Stuart A Scott (SA)

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.

Richard C Shelton (RC)

Department of Psychiatry, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.

Kristin Wiisanen Weitzel (KW)

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA.

Julie A Johnson (JA)

Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, FL, USA.

Josh F Peterson (JF)

Departments of Biomedical Informatics and Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Philip E Empey (PE)

Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, PA, USA.

Todd C Skaar (TC)

Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, USA.

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