Pharmacogenetics in clinical practice: how far have we come and where are we going?

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

• 1  Collins FS, McKusick VA. Implications of the human genome project for medical science. JAMA285(5),540–544 (2001).
  Medline CASGoogle Scholar
• 2  Ramsey BW, Davies J, Mcelvaney NG et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N. Engl. J. Med.365(18),1663–1672 (2011).
  Medline CASGoogle Scholar
• 3  Rubin EH, Gilliland DG. Drug development and clinical trials – the path to an approved cancer drug. Nat. Rev. Clin. Oncol.9(4),215–222 (2012).
  Medline CASGoogle Scholar
• 4  Asselbergs FW, Guo Y, van Iperen EP et al. Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci. Am. J. Hum. Genet.91(5),823–838 (2012).
  Medline CASGoogle Scholar
• 5  Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat. Genet.37(2),161–165 (2005).
  Medline CASGoogle Scholar
• 6  Nicholls SJ, Brewer HB, Kastelein JJ et al. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA306(19),2099–2109 (2011).
  Medline CASGoogle Scholar
• 7  Do RQ, Vogel RA, Schwartz GG. PCSK9 inhibitors: potential in cardiovascular therapeutics. Curr. Cardiol. Rep.15(3),345 (2013).
  MedlineGoogle Scholar
• 8  Relling MV, Klein TE. CPIC: clinical pharmacogenetics implementation consortium of the pharmacogenomics research network. Clin. Pharmacol. Ther.89(3),464–467 (2011).▪▪ Describes the premise of goals of the Clinical Pharmacogenetics Implementation Consortium, which seeks to advance clinical implementation of pharmacogenetics by providing guidelines to assist the clinician in using pharmacogenetic information in the clinical setting.
  Medline CASGoogle Scholar
• 9  Relling MV, Gardner EE, Sandborn WJ et al. Clinical pharmacogenetics implementation consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin. Pharmacol. Ther.89(3),387–391 (2011).
  Medline CASGoogle Scholar
• 10  Scott SA, Sangkuhl K, Gardner EE et al. Clinical pharmacogenetics implementation consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin. Pharmacol. Ther.90(2),328–332 (2011).
  Medline CASGoogle Scholar
• 11  Johnson JA, Gong L, Whirl-Carrillo M et al. Clinical pharmacogenetics implementation consortium guidelines for CYP2C9 and VKORC1 genotypes and warfarin dosing. Clin. Pharmacol. Ther.90(4),625–629 (2011).
  Medline CASGoogle Scholar
• 12  Crews KR, Gaedigk A, Dunnenberger HM et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin. Pharmacol. Ther.91(2),321–326 (2012).
  Medline CASGoogle Scholar
• 13  Martin MA, Klein TE, Dong BJ, Pirmohamed M, Haas DW, Kroetz DL. Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and abacavir dosing. Clin. Pharmacol. Ther.91(4),734–738 (2012).
  Medline CASGoogle Scholar
• 14  Wilke RA, Ramsey LB, Johnson SG et al. The clinical pharmacogenomics implementation consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy. Clin. Pharmacol. Ther.92(1),112–117 (2012).
  Medline CASGoogle Scholar
• 15  Hershfield MS, Callaghan JT, Tassaneeyakul W et al. Clinical pharmacogenetics implementation consortium guidelines for human leukocyte antigen-B genotype and allopurinol dosing. Clin. Pharmacol. Ther.93(2),153–158 (2013).
  Medline CASGoogle Scholar
• 16  Hicks JK, Swen JJ, Thorn CF et al. Clinical pharmacogenetics implementation consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin. Pharmacol. Ther.93(5),402–408 (2013).
  Medline CASGoogle Scholar
• 17  Gazzard BG, Anderson J, Babiker A et al. British HIV Association Guidelines for the treatment of HIV-1-infected adults with antiretroviral therapy 2008. HIV Med.9(8),563–608 (2008).
  Medline CASGoogle Scholar
• 18  Thompson MA, Aberg JA, Hoy JF et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA308(4),387–402 (2012).
  Medline CASGoogle Scholar
• 19  Mallal S, Phillips E, Carosi G et al.HLA-B*5701 screening for hypersensitivity to abacavir. N. Engl. J. Med.358(6),568–579 (2008).▪▪ Describes the first large, randomized controlled trial testing a pharmacogenetic-guided versus usual care approach. The study specifically showed that HLA-B*5701 genotyping to guide use of abacavir could significantly impact the development of abacavir hypersensitivity reactions.
  MedlineGoogle Scholar
• 20  Crews KR, Cross SJ, McCormick JN et al. Development and implementation of a pharmacist-managed clinical pharmacogenetics service. Am. J. Health Syst. Pharm.68(2),143–150 (2011).
  MedlineGoogle Scholar
• 21  Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College of gastroenterology, practice parameters committee. Am. J. Gastroenterol.105(3),501–523; quiz 524 (2010).
  MedlineGoogle Scholar
• 22  Pulley JM, Denny JC, Peterson JF et al. Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project. Clin. Pharmacol. Ther.92(1),87–95 (2012).▪ Provides detailed insights into the development and implementation of a pre-emptive genotyping pharmacogenetics implementation program in a large academic health center.
  Medline CASGoogle Scholar
• 23  Johnson JA, Burkley BM, Langaee TY, Clare-Salzler MJ, Klein TE, Altman RB. Implementing personalized medicine: Development of a cost-effective custom pharmacogenetics genotyping array. Clin. Pharmacol. Ther.92(4),437–439 (2012).
  Medline CASGoogle Scholar
• 24  Mrazek DA. Psychiatric pharmacogenomic testing in clinical practice. Dialogues Clin. Neurosci.12(1),69–76 (2010).
  MedlineGoogle Scholar
• 25  Roberts JD, Wells GA, Le May MR et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. Lancet379(9827),1705–1711 (2012).
  Medline CASGoogle Scholar
• 26  Scott SA. Clinical pharmacogenomics: opportunities and challenges at point of care. Clin. Pharmacol. Ther.93(1),33–35 (2013).
  Medline CASGoogle Scholar
• 27  O‘Connor SK, Ferreri SP, Michaels NM et al. Exploratory planning and implementation of a pilot pharmacogenetic program in a community pharmacy. Pharmacogenomics13(8),955–962 (2012).
  Google Scholar
• 28  O‘Donnell PH, Bush A, Spitz J et al. The 1200 patients project: creating a new medical model system for clinical implementation of pharmacogenomics. Clin. Pharmacol. Ther.92(4),446–449 (2012).
  MedlineGoogle Scholar
• 29  Lesko LJ, Zineh I. DNA, drugs and chariots: on a decade of pharmacogenomics at the US FDA. Pharmacogenomics11(4),507–512 (2010).
  Google Scholar
• 30  Lesko LJ, Johnson JA. Academia at the crossroads: education and training in pharmacogenomics. Pers. Med.9,497–506 (2012).
  CASGoogle Scholar
• 31  Stanek EJ, Sanders CL, Taber KA et al. Adoption of pharmacogenomic testing by US physicians: results of a nationwide survey. Clin. Pharmacol. Ther.91(3),450–458 (2012).▪ Describes results of a physician survey regarding knowledge of pharmacogenetics, acceptance of its importance and likelihood to order a pharmacogenetic test in the near future. Highlights the likely acceptance but educational challenges for clinical implementation of pharmacogenetics.
  Medline CASGoogle Scholar
• 32  Haga SB, Burke W, Ginsburg GS, Mills R, Agans R. Primary care physicians‘ knowledge of and experience with pharmacogenetic testing. Clin. Genet.82(4),388–394 (2012).▪ Another physician survey that highlights general recognition of the importance of pharmacogenetics on the part of physicians, but also their lack of knowledge and comfort with using pharmacogenetic information.
  Medline CASGoogle Scholar
• 33  Anderson JL, Adams CD, Antman EM et al. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation123(18),e426–e579 (2011).
  MedlineGoogle Scholar
• 34  Levine GN, Bates ER, Blankenship JC et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation124(23),e574–e651 (2011).
  MedlineGoogle Scholar
• 35  Wright RS, Anderson JL, Adams CD et al. 2011 ACCF/AHA focused update of the guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines developed in collaboration with the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J. Am. Coll. Cardiol.57(19),1920–1959 (2011).
  MedlineGoogle Scholar
• 36  Holbrook A, Schulman S, Witt DM et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis (9th Edition): American College of chest physicians evidence-based clinical practice guidelines. Chest141(Suppl. 2),e152S–e184S (2012).
  Medline CASGoogle Scholar
• 37  French B, Joo J, Geller NL et al. Statistical design of personalized medicine interventions: the Clarification of Optimal Anticoagulation through Genetics (COAG) trial. Trials11,108 (2010).
  MedlineGoogle Scholar
• 38  van Schie RM, Wadelius MI, Kamali F et al. Genotype-guided dosing of coumarin derivatives: the European pharmacogenetics of anticoagulant therapy (EU-PACT) trial design. Pharmacogenomics10(10),1687–1695 (2009).
  CASGoogle Scholar
• 39  Relling MV, Altman RB, Goetz MP, Evans WE. Clinical implementation of pharmacogenomics: overcoming genetic exceptionalism. Lancet Oncol.11(6),507–509 (2010).
  MedlineGoogle Scholar
• 40  Altman RB. Pharmacogenomics: “noninferiority” is sufficient for initial implementation. Clin. Pharmacol. Ther.89(3),348–350 (2011).▪ Commentary that takes a strong position against the apparently high bar being set for use of genetic information (including pharmacogenetics) in clinical practice.
  Medline CASGoogle Scholar
• 41  Binkhorst L, van Gelder T, Mathijssen RH. Individualization of tamoxifen treatment for breast carcinoma. Clin. Pharmacol. Ther.92(4),431–433 (2012).
  Medline CASGoogle Scholar
• 42  Veenstra DL, Roth JA, Garrison LP Jr, Ramsey SD, Burke W. A formal risk–benefit framework for genomic tests: facilitating the appropriate translation of genomics into clinical practice. Genet. Med.12(11),686–693 (2010).▪▪ Analytic framework proposed for how clinicians can deal with genetic and pharmacogenetic examples where the evidence is insufficient to clearly recommend for or against genetic testing. For cases of insufficient evidence, proposes a model for balancing risk–benefit of genetic testing against the level of uncertainty.
  MedlineGoogle Scholar
• 43  Khoury MJ, Coates RJ, Evans JP. Evidence-based classification of recommendations on use of genomic tests in clinical practice: dealing with insufficient evidence. Genet. Med.12(11),680–683 (2010).
  MedlineGoogle Scholar
• 44  Haga SB. Ethical, legal, and social challenges to applied pharmacogenetics. In: Pharmacogenomics. Applications to Patient Care. McLeod HL (Eds). American College of Clinical Pharmacy, KS, USA, 273–297 (2009).
  Google Scholar
• 101  US FDA Table of Pharmacogenomic Biomarkers in Drug Labels. www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm
  Google Scholar
• 102  The Pharmacogenomics Knowledgebase. www.PharmGKB.org
  Google Scholar
• 103  Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-infected Adults and Adolescents (2011). www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
  Google Scholar