Precision Medicine at the University of Alabama at Birmingham: Laying the Foundational Processes Through Implementation of Genotype-Guided Antiplatelet Therapy

Overview

Journal Clin Pharmacol Ther

Publisher Wiley

Specialty Pharmacology

Date 2017 Jan 27

PMID 28124392

Citations 13

Authors

S Harada

Y Zhou

S Duncan

A R Armstead

G M Coshatt

C Dillon

B C Brott

J Willig

J A Alsip

W B Hillegass

N A Limdi

Affiliations

Soon will be listed here.

Abstract

Precision medicine entails tailoring treatment based on patients' unique characteristics. As drug therapy constitutes the cornerstone of treatment for most chronic diseases, pharmacogenomics (PGx), the study of genetic variation influencing individual response to drugs, is an important component of precision medicine. Over the past decade investigations have identified genes and single-nucleotide polymorphisms (SNPs) and quantified their effect on drug response. Parallel development of point-of-care (POC) genotyping platforms has enabled the interrogation of the genes/SNPs within a timeline conducive to the provision of care. Despite these advances, the pace of integration of genotype-guided drug therapy (GGTx) into practice has faced significant challenges. These include difficulty in identifying SNPs with sufficiently robust evidence to guide clinical decision making, lack of clinician training on how to order and use genotype data, lack of clinical decision support (CDS) to guide treatment, and limited reimbursement. The University of Alabama at Birmingham's (UAB) efforts in precision medicine were initiated to address these challenges and improve the health of the racially diverse patients we treat.

Citing Articles

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References

James S, Akerblom A, Cannon C, Emanuelsson H, Husted S, Katus H . Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2009; 157(4):599-605. DOI: 10.1016/j.ahj.2009.01.003. View

Caudle K, Dunnenberger H, Freimuth R, Peterson J, Burlison J, Whirl-Carrillo M . Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Genet Med. 2016; 19(2):215-223. PMC: 5253119. DOI: 10.1038/gim.2016.87. View

Muller D, Kekin I, Kao A, Brandl E . Towards the implementation of CYP2D6 and CYP2C19 genotypes in clinical practice: update and report from a pharmacogenetic service clinic. Int Rev Psychiatry. 2013; 25(5):554-71. DOI: 10.3109/09540261.2013.838944. View

Hicks J, Stowe D, Willner M, Wai M, Daly T, Gordon S . Implementation of Clinical Pharmacogenomics within a Large Health System: From Electronic Health Record Decision Support to Consultation Services. Pharmacotherapy. 2016; 36(8):940-8. DOI: 10.1002/phar.1786. View

Thygesen K, Alpert J, Jaffe A, Chaitman B, White H, Katus H . Third universal definition of myocardial infarction. Circulation. 2012; 126(16):2020-35. DOI: 10.1161/CIR.0b013e31826e1058. View

Cutlip D, Windecker S, Mehran R, Boam A, Cohen D, van Es G . Clinical end points in coronary stent trials: a case for standardized definitions. Circulation. 2007; 115(17):2344-51. DOI: 10.1161/CIRCULATIONAHA.106.685313. View

. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993; 329(10):673-82. DOI: 10.1056/NEJM199309023291001. View

Mega J, Simon T, Collet J, Anderson J, Antman E, Bliden K . Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010; 304(16):1821-30. PMC: 3048820. DOI: 10.1001/jama.2010.1543. View

Hoffman J, Dunnenberger H, Hicks J, Caudle K, Whirl Carrillo M, Freimuth R . Developing knowledge resources to support precision medicine: principles from the Clinical Pharmacogenetics Implementation Consortium (CPIC). J Am Med Inform Assoc. 2016; 23(4):796-801. PMC: 6080683. DOI: 10.1093/jamia/ocw027. View

10.

Holmes Jr D, Dehmer G, Kaul S, Leifer D, OGara P, Stein C . ACCF/AHA Clopidogrel clinical alert: approaches to the FDA "boxed warning": a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents and the American Heart Association. Circulation. 2010; 122(5):537-57. DOI: 10.1161/CIR.0b013e3181ee08ed. View

11.

Wiisanen Weitzel K, Alexander M, Bernhardt B, Calman N, Carey D, Cavallari L . The IGNITE network: a model for genomic medicine implementation and research. BMC Med Genomics. 2016; 9:1. PMC: 4700677. DOI: 10.1186/s12920-015-0162-5. View

12.

Seto A, Kenyon K, Wittkowsky A . Discrepancies in identification of major bleeding events in patients taking warfarin. Pharmacotherapy. 2008; 28(9):1098-103. DOI: 10.1592/phco.28.9.1098. View

13.

Shuldiner A, OConnell J, Bliden K, Gandhi A, Ryan K, Horenstein R . Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009; 302(8):849-57. PMC: 3641569. DOI: 10.1001/jama.2009.1232. View

14.

Haga S, Allen LaPointe N, Cho A, Reed S, Mills R, Moaddeb J . Pilot study of pharmacist-assisted delivery of pharmacogenetic testing in a primary care setting. Pharmacogenomics. 2014; 15(13):1677-86. PMC: 4280849. DOI: 10.2217/pgs.14.109. View

15.

Farid N, Kurihara A, Wrighton S . Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans. J Clin Pharmacol. 2009; 50(2):126-42. DOI: 10.1177/0091270009343005. View

16.

Vladutiu G . The FDA announces new drug labeling for pharmacogenetic testing: is personalized medicine becoming a reality?. Mol Genet Metab. 2007; 93(1):1-4. DOI: 10.1016/j.ymgme.2007.10.133. View

17.

Scott S, Sangkuhl K, Stein C, Hulot J, Mega J, Roden D . Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013; 94(3):317-23. PMC: 3748366. DOI: 10.1038/clpt.2013.105. View

18.

Pinnock H, Epiphaniou E, Sheikh A, Griffiths C, Eldridge S, Craig P . Developing standards for reporting implementation studies of complex interventions (StaRI): a systematic review and e-Delphi. Implement Sci. 2015; 10:42. PMC: 4393562. DOI: 10.1186/s13012-015-0235-z. View

19.

ODonnell P, Danahey K, Jacobs M, Wadhwa N, Yuen S, Bush A . Adoption of a clinical pharmacogenomics implementation program during outpatient care--initial results of the University of Chicago "1,200 Patients Project". Am J Med Genet C Semin Med Genet. 2014; 166C(1):68-75. PMC: 4000170. DOI: 10.1002/ajmg.c.31385. View

20.

Hicks K, Stockbridge N, Targum S, Temple R . Bleeding Academic Research Consortium consensus report: the Food and Drug Administration perspective. Circulation. 2011; 123(23):2664-5. DOI: 10.1161/CIRCULATIONAHA.111.032433. View