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

被引：61

作者：

Cavallari, Larisa H. ^{[1
,2
]}

Van Driest, Sara L. ^{[3
,4
]}

Prows, Cynthia A. ^{[5
]}

Bishop, Jeffrey R. ^{[6
]}

Limdi, Nita A. ^{[7
,8
]}

Pratt, Victoria M. ^{[9
]}

Ramsey, Laura B. ^{[5
]}

Smith, D. Max ^{[1
,2
]}

Tuteja, Sony ^{[10
]}

Duong, Benjamin Q. ^{[1
,2
]}

Hicks, J. Kevin ^{[11
]}

Lee, James C. ^{[12
]}

Obeng, Aniwaa Owusu ^{[13
]}

Beitelshees, Amber L. ^{[14
]}

Bell, Gillian C. ^{[15
]}

Blake, Kathryn ^{[16
]}

Crona, Daniel J. ^{[17
,18
]}

Dressler, Lynn ^{[15
]}

Gregg, Ryan A. ^{[19
]}

Hines, Lindsay J. ^{[20
,21
,22
]}

Scott, Stuart A. ^{[23
,24
]}

Shelton, Richard C. ^{[25
]}

Weitzel, Kristin Wiisanen ^{[1
,2
]}

Johnson, Julie A. ^{[1
,2
]}

Peterson, Josh F. ^{[26
,27
]}

Empey, Philip E. ^{[28
]}

Skaar, Todd C. ^{[29
]}

机构：

[1] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32611 USA

[2] Univ Florida, Ctr Pharmacogen, Gainesville, FL 32611 USA

[3] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA

[4] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA

[5] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

[6] Univ Minnesota, Dept Expt & Clin Pharmacol, Minneapolis, MN USA

[7] Univ Alabama Birmingham, Dept Neurol, Sch Med, UAB Stn, Birmingham, AL 35294 USA

[8] Univ Alabama Birmingham, Hugh Kaul Personalized Med Inst, Birmingham, AL USA

[9] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

[10] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[11] H Lee Moffitt Canc Ctr & Res Inst, Dept Individualized Canc Management, Tampa, FL USA

[12] Univ Illinois, Dept Pharm Practice, Chicago, IL USA

[13] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA

[14] Univ Maryland, Dept Med, Baltimore, MD 21201 USA

[15] Mission Hlth, Personalized Med Program, Asheville, NC USA

[16] Nemours Childrens Specialty Care, Ctr Pharmacogen & Translat Res, Jacksonville, FL USA

[17] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC 27515 USA

[18] Univ N Carolina, Ctr Pharmacogen & Individualized Therapy, Chapel Hill, NC 27515 USA

[19] OneOme, Minneapolis, MN USA

[20] Univ North Dakota, Dept Psychol, Grand Forks, ND 58202 USA

[21] Sanford Brain & Spine Ctr, Fargo, ND USA

[22] Sanford Imagenet, Fargo, ND USA

[23] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[24] Sema4, Stamford, CT USA

[25] Univ Alabama Birmingham, Sch Med, Dept Psychiat, Birmingham, AL USA

[26] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA

[27] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA

[28] Univ Pittsburgh, Dept Pharm & Therapeut, Pittsburgh, PA USA

[29] Indiana Univ Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA

来源：

GENETICS IN MEDICINE | 2019年 / 21卷 / 10期

基金：

美国国家卫生研究院;

关键词：

pharmacogenetics; implementation; CYP2D6; opioids; antidepressants; CONSORTIUM CPIC GUIDELINE; COPY NUMBER; PHARMACOGENETICS; CODEINE; MORPHINE; PHARMACOKINETICS; POLYMORPHISMS; TRAMADOL; ALLELE;

D O I：

10.1038/s41436-019-0484-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：2255 / 2263

页数：9

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