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Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.


CiteScore 2018: 1.01

SCImago Journal Rank (SJR) 2018: 0.277
Source Normalized Impact per Paper (SNIP) 2018: 0.446

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2363-8915
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Volume 31, Issue 2

Issues

Volume 34 (2019)

The integration and interpretation of pharmacogenomics – a comparative study between the United States of America and Europe: towards better health care

Mark J. Bartlett / Elizabeth A. Shephard
  • Institute of Structural and Molecular Biology, University College London, Gower Street, London, UK
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-06-07 | DOI: https://doi.org/10.1515/dmpt-2015-0044

Abstract

The study of pharmacogenomics has, by harnessing sequence information from human genomes, the potential to lead to novel approaches in drug discovery, an individualized application of drug therapy, and new insights into disease prevention. For this potential to be realized results need to be interpreted to the prescriber into a format which dictates an action. This mini review briefly describes the history, the regulatory environment, opinions towards, and implementation, integration and interpretation of pharmacogenomics in the United States of America and Europe. The article discusses also how interpretation of pharmacogenomics could move forward to better implementation in health care.

Keywords: implementation; pharmacogenetics; pharmacogenomics; regulatory bodies

References

  • 1.

    FDA/ICH. E15 Definitions for genomic biomarkers, pharmacogenomics, pharmacogenetics, genomic data, and sample coding categories. Guidance 2008;27:359–63.Google Scholar

  • 2.

    Mancinelli L, Cronin M, Sadee W. Pharmacogenomics: the promise of personalized medicine. AAPS PharmSci 2000;2:E4.CrossrefGoogle Scholar

  • 3.

    Daly AK. Pharmacogenetics and human genetic polymorphisms. Biochem J 2010;429:435–49.Google Scholar

  • 4.

    Vogel F. Moderne problem der Humangenetik. Ergeb Inn Med Kinderheilkd 1959;12:52–125.Google Scholar

  • 5.

    Tarlov AR, Brewer GJ, Carson PE, Alving AS. Primaquine sensitivity. Glucose-6-phosphate dehydrogenase deficiency: an inborn error of metabolism of medical and biological significance. Arch Intern Med 1962;109:209–34.Google Scholar

  • 6.

    Vesell ES, Page JG. Genetic control of drug levels in man: phenylbutazone. Science 1968;159:1479–80.Google Scholar

  • 7.

    Gonzalez FJ, Skoda RC, Kimura S, Umeno M, Zanger UM, Nebert DW, et al. Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature 1988;331:442–6.Google Scholar

  • 8.

    Kagimoto M, Heim M, Kagimoto K, Zeugin T, Meyer UA. Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. J Biol Chem 1990;265:17209–14.Google Scholar

  • 9.

    Pirmohamed M, Park BK. Genetic susceptibility to adverse drug reactions. Trends Pharmacol Sci 2001;22:298–305.Google Scholar

  • 10.

    McDonagh EM, Whirl-Carrillo M, Garten Y, Altman RB, Klein TE. From pharmacogenomic knowledge acquisition to clinical applications: the PharmGKB as a clinical pharmacogenomic biomarker resource. Biomark Med 2011;5:795–806.Google Scholar

  • 11.

    Vesell ES. Advances in pharmacogenetics and pharmacogenomics. J Clin Pharmacol 2000;40:930–8.Google Scholar

  • 12.

    Motulsky AG, Qi M. Pharmacogenetics, pharmacogenomics and ecogenetics. J Zhejiang Univ Sci B 2006;7:169–70.Google Scholar

  • 13.

    Sim SC, Ingelman-Sundberg M. The Human Cytochrome P450 (CYP) Allele Nomenclature website: a peer-reviewed database of CYP variants and their associated effects. Hum Genomics 2010;4:278–81.Google Scholar

  • 14.

    Relling MV, Klein TE. CPIC: clinical pharmacogenetics implementation consortium of the pharmacogenomics research network. Clin Pharmacol Ther 2011;89:464–7.Google Scholar

  • 15.

    GenomeWeb Staff Reporter. Personalis Licenses PharmGKB Database, Launches Genomic Services [Internet]. GenomeWeb. [cited 2015 Nov 27]. Available at: http://www.genomeweb.com/informatics/personalis-licenses-pharmgkb-database-launches-genomic-services.

  • 16.

    Food and Drug Administration. Table of pharmacogenomic biomarkers in drug labeling [Internet]. [cited 2015 Nov 29]. Available at: http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.htm.

  • 17.

    Relling MV, Evans WE. Pharmacogenomics in the clinic. Nature 2015;526:343–50.Google Scholar

  • 18.

    Scott SA. Personalizing medicine with clinical pharmacogenetics. Genet Med 2011;13:987–95.Google Scholar

  • 19.

    Coleman H, Ashcraft K. Genelex Corporation. Pharmacogenomics 2008. p. 469–75.

  • 20.

    European Medicines Agency. Mandate, objectives and rules of procedure for the CHMP PG Working Party [Internet]. 2009 [cited 2015 Nov 29]. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2010/01/WC500069715.pdf.

  • 21.

    Swen JJ, Wilting I, de Goede AL, Grandia L, Mulder H, Touw DJ, et al. Pharmacogenetics: from bench to byte. Clin Pharmacol Ther 2008;83:781–7.Google Scholar

  • 22.

    Hall I. Conference scene: UK pharmacogenetics and stratified medicine network. Pharmacogenomics 2012;13:19–20.Google Scholar

  • 23.

    Manolopoulos VG, Dechairo B, Huriez A, Kühn A, Llerena A, van Schaik RH, et al. Pharmacogenomics and personalized medicine in clinical practice. Pharmacogenomics 2011;12:597–610.Google Scholar

  • 24.

    Ehmann F, Caneva L, Prasad K, Paulmichl M, Maliepaard M, Llerena A, et al. Pharmacogenomic information in drug labels: European Medicines Agency perspective. Pharmacogenomics J 2015;15:201–10.Google Scholar

  • 25.

    Prasad K, Breckenridge A. Pharmacogenomics: a new clinical or regulatory paradigm? European experiences of pharmacogenomics in drug regulation and regulatory initiatives. Drug Discov Today 2011;16:867–72.Google Scholar

  • 26.

    Maliepaard M, Nofziger C, Papaluca M, Zineh I, Uyama Y, Prasad K, et al. Pharmacogenetics in the evaluation of new drugs: a multiregional regulatory perspective. Nat Rev Drug Discov 2013;12:103–15.Google Scholar

  • 27.

    European Medicines Agency. Guideline on the use of pharmacogenetic methodologies in the pharmacokinetic evaluation of medicinal products [Internet]. [cited 2015 Nov 29]. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/02/WC500121954.pdf#EMA pharmacogenetic guideline for pharma%28pdf%29.

  • 28.

    European Medicines Agency. Pharmacogenomics Working Party [Internet]. [cited 2015 Nov 29]. Available at: http://www.ema.europa.eu/ema/index.jsp?curl=pages/contacts/CHMP/people_listing_000018.jsp&mid=WC0b01ac0580028d91.

  • 29.

    Higgs J, Gambhir N, Ramsden SC, Poulton K, Newman WG. Pharmacogenetic testing in the United Kingdom genetics and immunogenetics laboratories. Genet Test Mol Biomarkers 2010;14:121–5.Google Scholar

  • 30.

    Kollek R, van Aken J, Feuerstein G, Schmedders M. Pharmacogenetics, adverse drug reactions and public health. Community Genet 2006;9:50–4.Google Scholar

  • 31.

    Shalala D. Protecting research subjects – what must be done. New Engl J Med 2000;343:808–10.Google Scholar

  • 32.

    Fleuren M, Wiefferink K, Paulussen T. Determinants of innovation within health care organizations: literature review and Delphi study. Int J Qual Health Care 2004;16:107–23.Google Scholar

  • 33.

    Fargher EA, Tricker K, Newman W, Elliott R, Roberts SA, Shaffer JL, et al. Current use of pharmacogenetic testing: a national survey of thiopurine methyltransferase testing prior to azathioprine prescription. J Clin Pharm Ther 2007;32:187–95.Google Scholar

  • 34.

    The Royal Society. Personalised medicines: hopes and realities [Internet]. [cited 2015 Nov 25]. Available at: https://royalsociety.org/∼/media/Royal_Society_Content/policy/publications/2005/9631.pdf.

  • 35.

    Haga SB, O’Daniel JM, Tindall GM, Lipkus IR, Agans R. Survey of US public attitudes toward pharmacogenetic testing. Pharmacogenomics J 2012;12:197–204.Google Scholar

  • 36.

    Stanek EJ, Sanders CL, Taber KA, Khalid M, Patel A, Verbrugge RR, et al. Adoption of pharmacogenomic testing by US physicians: results of a nationwide survey. Clin Pharmacol Ther 2012;91:450–8.Google Scholar

  • 37.

    Dodson C, Van Riper M. Analysis of clinicians’ attitudes towards pharmacogenomics. Per Med 2011;8:533–40.Google Scholar

  • 38.

    Hedgecoe AM. Context, ethics and pharmacogenetics. Stud Hist Philos Sci Part C Stud Hist Philos Biol Biomed Sci 2006;37:566–82.Google Scholar

  • 39.

    Bartlett MJ, Green DW, Shephard EA. Pharmacogenetic testing in the UK clinical setting. Lancet 2013;381:1903.Google Scholar

  • 40.

    Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K, Seger AC, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. J Am Med Assoc 2003;289:1107–16.Google Scholar

  • 41.

    United Health. Personalized medicine: trends and prospects for the new science of genetic testing and molecular diagnostics [Internet]. [cited 2015 Nov 29]. Available at: http://www.unitedhealthgroup.com/∼/media/uhg/pdf/2012/unh-working-paper-7.ashx.

  • 42.

    Powell KP, Cogswell WA, Christianson CA, Dave G, Verma A, Eubanks S, et al. Primary care physicians’ awareness, experience and opinions of direct-to-consumer genetic testing. J Genet Couns 2012;21:113–26.Google Scholar

  • 43.

    Fears R, ter Meulen V. The perspective from EASAC and FEAM on direct-to-consumer genetic testing for health-related purposes. Eur J Hum Genet 2013;21:703–7.Google Scholar

  • 44.

    Hicks JK, Crews KR, Hoffman JM, Kornegay NM, Wilkinson MR, Lorier R, et al. A clinician-driven automated system for integration of pharmacogenetic interpretations into an electronic medical record. Clin Pharmacol Ther 2012;92:563–6.Google Scholar

  • 45.

    O’Donnell PH, Bush A, Spitz J, Danahey K, Saner D, Das S, et al. The 1200 patients project: creating a new medical model system for clinical implementation of pharmacogenomics. Clin Pharmacol Ther 2012;92:446–9.Google Scholar

  • 46.

    Peterson JF, Bowton E, Field JR, Beller M, Mitchell J, Schildcrout J, et al. Electronic health record design and implementation for pharmacogenomics: a local perspective. Genet Med 2013;15:833–41.Google Scholar

  • 47.

    Ullman-Cullere MH, Mathew JP. Emerging landscape of genomics in the Electronic Health Record for personalized medicine. Hum Mutat 2011;32:512–6.Google Scholar

  • 48.

    Roberts JD, Wells GA, Le May MR, Labinaz M, Glover C, Froeschl M, et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. Lancet 2012;379:1705–11.Google Scholar

  • 49.

    Pulley JM, Denny JC, Peterson JF, Bernard GR, Vnencak-Jones CL, Ramirez AH, et al. Operational implementation of prospective genotyping for personalized medicine: the design of the Vanderbilt PREDICT project. Clin Pharmacol Ther 2012;92:87–95.Google Scholar

  • 50.

    Van Driest SL, Shi Y, Bowton EA, Schildcrout JS, Peterson JF, Pulley J, et al. Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clin Pharmacol Ther 2014;95:423–31.Google Scholar

  • 51.

    Dunnenberger HM, Crews KR, Hoffman JM, Caudle KE, Broeckel U, Howard SC, et al. Preemptive clinical pharmacogenetics implementation: current programs in five US medical centers. Annu Rev Pharmacol Toxicol 2015;55:89–106.Google Scholar

  • 52.

    Swen JJ, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee AH, Mulder H, et al. Pharmacogenetics: from bench to byte – an update of guidelines. Clin Pharmacol Ther 2011;89:662–73.Google Scholar

  • 53.

    Samwald M. Positive evaluation of U-PGx proposal! [Internet]. U-PGx. [cited 2015 Nov 29]. Available at: http://upgx.eu/?p=158.

  • 54.

    Welch BM, Kawamoto K. Clinical decision support for genetically guided personalized medicine: a systematic review. J Am Med Informatics Assoc 2012;20:388–400.Google Scholar

  • 55.

    Crews KR, Hicks JK, Pui C-H, Relling MV, Evans WE. Pharmacogenomics and individualized medicine: translating science into practice. Clin Pharmacol Ther 2012;92:467–75.Google Scholar

  • 56.

    Huckvale C, Car J, Akiyama M, Jaafar S, Khoja T, Bin Khalid A, et al. Information technology for patient safety. Qual Saf Health Care 2010;19(Suppl 2):i25–33.Google Scholar

  • 57.

    Nanji KC, Slight SP, Seger DL, Cho I, Fiskio JM, Redden LM, et al. Overrides of medication-related clinical decision support alerts in outpatients. J Am Med Inform Assoc 2014;21:487–91.Google Scholar

  • 58.

    Cresswell K, Coleman J, Slee A, Morrison Z, Sheikh A. A toolkit to support the implementation of electronic prescribing systems into UK hospitals: preliminary recommendations. J R Soc Med 2014;107:8–13.Google Scholar

  • 59.

    Genomics England. Genomics England launched, mapping DNA to better understand cancer, rare and infectious diseases [Internet]. [cited 2015 Nov 29]. Available at: http://www.genomicsengland.co.uk/genomics-england-launch/.

  • 60.

    Harrison MB, Graham ID, van den Hoek J, Dogherty EJ, Carley ME, Angus V. Guideline adaptation and implementation planning: a prospective observational study. Implement Sci 2013;8:49.Google Scholar

About the article

Received: 2015-12-04

Accepted: 2016-04-06

Published Online: 2016-06-07

Published in Print: 2016-06-01


Citation Information: Drug Metabolism and Personalized Therapy, Volume 31, Issue 2, Pages 91–96, ISSN (Online) 2363-8915, ISSN (Print) 2363-8907, DOI: https://doi.org/10.1515/dmpt-2015-0044.

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