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      Prioritizing Genomic Applications for Action by Level of Evidence: A Horizon-Scanning Method

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          Abstract

          As evidence accumulates on the use of genomic tests and other health-related applications of genomic technologies, decision makers may increasingly seek support in identifying which applications have sufficiently robust evidence to suggest they might be considered for action. As an interim working process to provide such support, we developed a horizon-scanning method that assigns genomic applications to tiers defined by availability of synthesized evidence. We illustrate an application of the method to pharmacogenomics tests.

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          Most cited references40

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          CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network.

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            Pharmacogenetics: from bench to byte--an update of guidelines.

            Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).
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              Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.

              Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 loss-of-function alleles impair formation of active metabolites, resulting in reduced platelet inhibition. In addition, CYP2C19 loss-of-function alleles confer increased risks for serious adverse cardiovascular (CV) events among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Guideline updates include emphasis on appropriate indication for CYP2C19 genotype-directed antiplatelet therapy, refined recommendations for specific CYP2C19 alleles, and additional evidence from an expanded literature review (updates at http://www.pharmgkb.org).
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                Author and article information

                Journal
                Clinical Pharmacology & Therapeutics
                Clin Pharmacol Ther
                Springer Science and Business Media LLC
                0009-9236
                1532-6535
                February 19 2014
                April 2014
                February 19 2014
                April 2014
                : 95
                : 4
                : 394-402
                Article
                10.1038/clpt.2013.226
                24398597
                ea8f8cbf-cd8f-4722-ae34-9a451ffa6cbc
                © 2014
                History

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