PG4KDS: a model for the clinical implementation of pre-emptive pharmacogenetics. Am J Med Genet C Semin Med Genet 2014 Mar;166C(1):45-55
Date
03/13/2014Pubmed ID
24619595Pubmed Central ID
PMC4056586DOI
10.1002/ajmg.c.31391Scopus ID
2-s2.0-84896319867 (requires institutional sign-in at Scopus site) 241 CitationsAbstract
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.
Author List
Hoffman JM, Haidar CE, Wilkinson MR, Crews KR, Baker DK, Kornegay NM, Yang W, Pui CH, Reiss UM, Gaur AH, Howard SC, Evans WE, Broeckel U, Relling MVAuthor
Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Aryl Hydrocarbon HydroxylasesCytochrome P-450 CYP2C19
Cytochrome P-450 CYP2D6
Electronic Health Records
Gene Dosage
Genetic Testing
Genotype
Humans
Medical Informatics Applications
Methyltransferases
Models, Theoretical
Organic Anion Transporters
Pharmacogenetics
Practice Patterns, Physicians'
Protein Array Analysis
