Preemptive Genotyping for Personalized Medicine: Design of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment Protocol

被引：227

作者：

Bielinski, Suzette J. ^{[1
]}

Olson, Janet E. ^{[1
]}

Pathak, Jyotishman ^{[1
]}

Weinshilboum, Richard M. ^{[2
,3
]}

Wang, Liewei ^{[2
]}

Lyke, Kelly J. ^{[1
]}

Ryu, Euijung ^{[1
]}

Targonski, Paul V. ^{[4
]}

Van Norstrand, Michael D. ^{[11
]}

Hathcock, Matthew A. ^{[1
]}

Takahashi, Paul Y. ^{[4
]}

McCormick, Jennifer B. ^{[1
,3
,5
]}

Johnson, Kiley J. ^{[3
]}

Maschke, Karen J. ^{[12
]}

Vitek, Carolyn R. Rohrer

Ellingson, Marissa S.

Wieben, Eric D. ^{[6
]}

Farrugia, Gianrico ^{[7
]}

Morrisette, Jody A. ^{[1
]}

Kruckeberg, Keri J. ^{[8
]}

Bruflat, Jamie K. ^{[8
]}

Peterson, Lisa M. ^{[8
]}

Blommel, Joseph H. ^{[8
]}

Skierka, Jennifer M. ^{[8
]}

Ferber, Matthew J. ^{[8
]}

Black, John L. ^{[8
]}

Baudhuin, Linnea M. ^{[8
]}

Klee, Eric W. ^{[1
]}

Ross, Jason L. ^{[9
]}

Veldhuizen, Tamra L.

Schultz, Cloann G.

Caraballo, Pedro J. ^{[5
]}

Freimuth, Robert R. ^{[1
]}

Chute, Christopher G. ^{[1
]}

Kullo, Iftikhar J. ^{[10
]}

机构：

[1] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA

[3] Mayo Clin, Ctr Individualized Med, Rochester, MN USA

[4] Mayo Clin, Div Primary Care Internal Med, Rochester, MN USA

[5] Mayo Clin, Div Gen Internal Med, Rochester, MN USA

[6] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN USA

[7] Mayo Clin, Div Gastroenterol, Rochester, MN USA

[8] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[9] Mayo Clin, Dept Informat Technol, Rochester, MN USA

[10] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA

[11] Mayo Clin Hlth Syst Franciscan Healthcare, Dept Gastroenterol, La Crosse, WI USA

[12] Hastings Ctr, Garrison, NY USA

来源：

MAYO CLINIC PROCEEDINGS | 2014年 / 89卷 / 01期

基金：

美国国家卫生研究院;

关键词：

IMPLEMENTATION CONSORTIUM; PHARMACOGENOMICS; KNOWLEDGE;

D O I：

10.1016/j.mayocp.2013.10.021

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: To report the design and implementation of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR). Patients and Methods: We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR. Results: The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance. Conclusion: This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice. (C) 2014 Mayo Foundation for Medical Education and Research

引用

页码：25 / 33

页数：9

共 16 条

[1] PharmGKB: a logical home for knowledge relating genotype to drug response phenotype [J].

Altman, Russ B. .

NATURE GENETICS, 2007, 39 (04) :426-426

[2]

[Anonymous], 2013, Table of Pharmacogenomic Biomarkers in Drug Labels

[3] Challenges in Implementing Genomic Medicine: The Mayo Clinic Center for Individualized Medicine [J].

Farrugia, G. ;

Weinshilboum, R. M. .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2013, 94 (02) :204-206

[4]

Flockhart D., DRUG INTERACTIONS CY

[5]

Gordon AS, 2012, 62 ANN M AM SOC HUM

[6] Primary care physicians' knowledge of and experience with pharmacogenetic testing [J].

Haga, S. B. ;

Burke, W. ;

Ginsburg, G. S. ;

Mills, R. ;

Agans, R. .

CLINICAL GENETICS, 2012, 82 (04) :388-394

[7] Electronic Medical Records for Genetic Research: Results of the eMERGE Consortium [J].

Kho, Abel N. ;

Pacheco, Jennifer A. ;

Peissig, Peggy L. ;

Rasmussen, Luke ;

Newton, Katherine M. ;

Weston, Noah ;

Crane, Paul K. ;

Pathak, Jyotishman ;

Chute, Christopher G. ;

Bielinski, Suzette J. ;

Kullo, Iftikhar J. ;

Li, Rongling ;

Manolio, Teri A. ;

Chisholm, Rex L. ;

Denny, Joshua C. .

SCIENCE TRANSLATIONAL MEDICINE, 2011, 3 (79)

[8]

New York Department of Health, ONC MOL CELL TUM MAR

[9] The Mayo Clinic Biobank: A Building Block for Individualized Medicine [J].

Olson, Janet E. ;

Ryu, Euijung ;

Johnson, Kiley J. ;

Koenig, Barbara A. ;

Maschke, Karen J. ;

Morrisette, Jody A. ;

Liebow, Mark ;

Takahashi, Paul Y. ;

Fredericksen, Zachary S. ;

Sharma, Ruchi G. ;

Anderson, Kari S. ;

Hathcock, Matthew A. ;

Carnahan, Jason A. ;

Pathak, Jyotishman ;

Lindor, Noralane M. ;

Beebe, Timothy J. ;

Thibodeau, Stephen N. ;

Cerhan, James R. .

MAYO CLINIC PROCEEDINGS, 2013, 88 (09) :952-962

[10] CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network [J].

Relling, M. V. ;

Klein, T. E. .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2011, 89 (03) :464-467

← 1 2 →