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      Incorporation of Pharmacogenomics into Routine Clinical Practice: the Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline Development Process

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          Abstract

          The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes genotype-based drug guidelines to help clinicians understand how available genetic test results could be used to optimize drug therapy. CPIC has focused initially on well-known examples of pharmacogenomic associations that have been implemented in selected clinical settings, publishing nine to date. Each CPIC guideline adheres to a standardized format and includes a standard system for grading levels of evidence linking genotypes to phenotypes and assigning a level of strength to each prescribing recommendation. CPIC guidelines contain the necessary information to help clinicians translate patient-specific diplotypes for each gene into clinical phenotypes or drug dosing groups. This paper reviews the development process of the CPIC guidelines and compares this process to the Institute of Medicine’s Standards for Developing Trustworthy Clinical Practice Guidelines.

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          Most cited references25

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          Pharmacogenomics knowledge for personalized medicine.

          The Pharmacogenomics Knowledgebase (PharmGKB) is a resource that collects, curates, and disseminates information about the impact of human genetic variation on drug responses. It provides clinically relevant information, including dosing guidelines, annotated drug labels, and potentially actionable gene-drug associations and genotype-phenotype relationships. Curators assign levels of evidence to variant-drug associations using well-defined criteria based on careful literature review. Thus, PharmGKB is a useful source of high-quality information supporting personalized medicine-implementation projects.
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            CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network.

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              Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing.

              Thiopurine methyltransferase (TPMT) activity exhibits monogenic co-dominant inheritance, with ethnic differences in the frequency of occurrence of variant alleles. With conventional thiopurine doses, homozygous TPMT-deficient patients (~1 in 178 to 1 in 3,736 individuals with two nonfunctional TPMT alleles) experience severe myelosuppression, 30-60% of individuals who are heterozygotes (~3-14% of the population) show moderate toxicity, and homozygous wild-type individuals (~86-97% of the population) show lower active thioguanine nucleolides and less myelosuppression. We provide dosing recommendations (updates at http://www.pharmgkb.org) for azathioprine, mercaptopurine (MP), and thioguanine based on TPMT genotype.
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                Author and article information

                Journal
                Curr Drug Metab
                Curr. Drug Metab
                CDM
                Current Drug Metabolism
                Bentham Science Publishers
                1389-2002
                1875-5453
                February 2014
                February 2014
                : 15
                : 2
                : 209-217
                Affiliations
                [1 ]Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
                [2 ]Department of Genetics, Stanford University, Palo Alto, California, USA
                [3 ]Centre for Addiction and Mental Health, Toronto, Canada
                [4 ]Department of Psychiatry, University of Toronto, Toronto, Canada
                [5 ]Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany
                [6 ]Department of Clinical Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology, University Hospital, Tuebingen, Germany
                [7 ]Department of Pharmacology, University of Extremadura, Cáceres, Spain
                [8 ]Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
                [9 ]Laboratory for Informatics Development, NIH Clinical Center, Bethesda, Maryland, USA
                [10 ]Laboratory for International Alliance on Genomic Research, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
                [11 ]National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
                [12 ]School of Chinese Medicine, China Medical University, Taichung, Taiwan
                [13 ]Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
                [14 ]Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA
                [15 ]Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden
                [16 ]Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden The Netherlands
                [17 ]Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA
                [18 ]Genomic Medicine Institute, Geisinger Health System, Danville, Pennsylvania, USA
                [19 ]Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Denver, Colorado, USA
                [20 ]Clinical Pharmacy Services, Kaiser Permanente Colorado, Denver, Colorado, USA
                Author notes
                [* ]Address correspondence to this author at 262 Danny Thomas Place MS: 313, Memphis, TN 38105, USA; Tel: 901-595-3994; Fax: 901-595-3125; E-mail: cpic@ 123456pharmgkb.org
                Article
                CDM-15-209
                10.2174/1389200215666140130124910
                3977533
                24479687
                9416b815-cb2a-478a-a754-29701ada8530
                © 2014 Bentham Science Publishers

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 September 2013
                : 11 October 2013
                : 21 January 2014
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                clinical practice guideline,guideline,pharmacogenetics,pharmacogenomics.

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