A Clinician-Driven Automated System for Integration of Pharmacogenetic Interpretations Into an Electronic Medical Record

Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Clinical Pharmacology &#38 Therapeutics (Impact Factor: 7.9). 09/2012; 92(5):563-6. DOI: 10.1038/clpt.2012.140
Source: PubMed


Advances in pharmacogenetic testing will expand the number of clinically important pharmacogenetic variants. Communication and interpretation of these test results are critical steps in implementation of pharmacogenetics into the clinic. Computational tools that integrate directly into the electronic medical record (EMR) are needed to translate the growing number of genetic variants into interpretive consultations to facilitate gene-based drug prescribing. Herein, we describe processes for incorporating pharmacogenetic tests and interpretations into the EMR for clinical practice.Clinical Pharmacology & Therapeutics (2012); advance online publication 19 September 2012. doi:10.1038/clpt.2012.140.

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Available from: Cyrine E Haidar, Jan 06, 2014
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    • "The purpose of the protocol is to selectively migrate microarray-based genotypes for clinically relevant genes into each patient's electronic medical record pre-emptively. By leveraging ‘look up’ translation tables created by the Translational Pharmacogenetics Project (TPP) [34], a PGRN-led initiative with the goal of operationalizing the work of the Clinical Pharmacogenetics Implementation Consortium (CPIC) [35] by translating widely accepted actionable PGx discoveries into real-world clinical practice, they assigned phenotypes to each unique CYP2D6 or TPMT diplotype based on assessments of functional allele activity [36]. "
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    ABSTRACT: In the post-genomic era, the rapid evolution of high-throughput genotyping technologies and the increased pace of production of genetic research data are continually prompting the development of appropriate informatics tools, systems and databases as we attempt to cope with the flood of incoming genetic information. Alongside new technologies that serve to enhance data connectivity, emerging information systems should contribute to the creation of a powerful knowledge environment for genotype-to-phenotype information in the context of translational medicine. In the area of pharmacogenomics and personalized medicine, it has become evident that database applications providing important information on the occurrence and consequences of gene variants involved in pharmacokinetics, pharmacodynamics, drug efficacy and drug toxicity will become an integral tool for researchers and medical practitioners alike. At the same time, two fundamental issues are inextricably linked to current developments, namely data sharing and data protection. Here, we discuss high-throughput and next-generation sequencing technology and its impact on pharmacogenomics research. In addition, we present advances and challenges in the field of pharmacogenomics information systems which have in turn triggered the development of an integrated electronic 'pharmacogenomics assistant'. The system is designed to provide personalized drug recommendations based on linked genotype-to-phenotype pharmacogenomics data, as well as to support biomedical researchers in the identification of pharmacogenomics-related gene variants. The provisioned services are tuned in the framework of a single-access pharmacogenomics portal.
    Full-text · Article · Jul 2014 · Open Biology
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    • "The text of each consult includes five standard sections with a placeholder for patient-specific comments to be manually added by the verifying pharmacist as needed. These five standard sections include a phenotype assignment section, an interpretation of the diplotype, a dosing recommendation section, an activity score section when appropriate, and a link to the PG4KDS webpage for more information [Hicks et al., 2012]. For example, for CYP2D6 and TPMT, Consult Builder contains a library of over 200 predefined clinical pharmacogenetic consults, which we have further translated into seven possible CYP2D6 and four possible TPMT phenotypes; that are then categorized as " routine " or " priority. "
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    ABSTRACT: Pharmacogenetics is frequently cited as an area for initial focus of the clinical implementation of genomics. Through the PG4KDS protocol, St. Jude Children's Research Hospital pre-emptively genotypes patients for 230 genes using the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array supplemented with a CYP2D6 copy number assay. The PG4KDS protocol provides a rational, stepwise process for implementing gene/drug pairs, organizing data, and obtaining consent from patients and families. Through August 2013, 1,559 patients have been enrolled, and four gene tests have been released into the electronic health record (EHR) for clinical implementation: TPMT, CYP2D6, SLCO1B1, and CYP2C19. These genes are coupled to 12 high-risk drugs. Of the 1,016 patients with genotype test results available, 78% of them had at least one high-risk (i.e., actionable) genotype result placed in their EHR. Each diplotype result released to the EHR is coupled with an interpretive consult that is created in a concise, standardized format. To support-gene based prescribing at the point of care, 55 interruptive clinical decision support (CDS) alerts were developed. Patients are informed of their genotyping result and its relevance to their medication use through a letter. Key elements necessary for our successful implementation have included strong institutional support, a knowledgeable clinical laboratory, a process to manage any incidental findings, a strategy to educate clinicians and patients, a process to return results, and extensive use of informatics, especially CDS. Our approach to pre-emptive clinical pharmacogenetics has proven feasible, clinically useful, and scalable. © 2014 Wiley Periodicals, Inc.
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    • "Efforts are underway, however, to address these common barriers . Examples are the ' 1200 Patients Project ' at the University of Chicago (O'Donnell et al., 2012), the personalized medicine programmes at the University of Florida and Stanford University (Johnson et al., 2012), PG4KDS at St Jude Children ' s Research Hospital (Crews et al., 2011;Hicks et al., 2012), and efforts to produce clinically relevant guidelines (CPIC (Relling & Klein, 2011)) and the Pharmacogenomics Working Group of the Royal Dutch Association for the Advancement of Pharmacy (Swen et al., 2011).and the sum of the values assigned to each allele produces the AS (Table 2). Briefl y, functional alleles comparable to that of the CYP2D6 * 1 reference are given a value of 1 and reduced function and null receive values of 0.5 and 0, respectively; gene duplications score double the value given for their single counterparts. "
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    ABSTRACT: Abstract Cytochrome P450 2D6 (CYP2D6) plays an important role in the metabolism and bioactivation of about 25% of clinically used drugs including many antidepressants, antipsychotics and opioids. CYP2D6 activity is highly variably ranging from no activity in so-called poor metabolizers to ultrarapid metabolism at the other end of the extreme of the activity distribution. A large portion of this variability can be explained by the highly polymorphic nature of the CYP2D6 gene locus for which > 100 variants and subvariants identified to date. Allele frequencies vary markedly between ethnic groups; some have exclusively or predominantly only been observed in certain populations. Pharmacogenetic testing holds the promise of individualizing drug therapy by identifying patients with CYP2D6 diplotypes that puts them at an increased risk of experiencing dose-related adverse events or therapeutic failure. Inferring a patient's CYP2D6 metabolic capacity, or phenotype, however, is a challenging task due to the complexity of the CYP2D6 gene locus. Allelic variation includes SNPs, small insertions and deletions, gene copy number variation and rearrangements with CYP2D7, a highly related non-functional gene. This review provides a summary of the intricacies of CYP2D6 variation and genotype analysis, knowledge that is invaluable for the translation of genotype into clinically useful information.
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