James M. Hoffman, Pharm.D., M.S., B.C.P.S. is an Associate Member in Pharmaceutical Sciences and the Medication Outcomes & Safety Officer at St. Jude Children's Research Hospital. He is also an associate professor at the University of Tennessee College of Pharmacy. He earned both his undergraduate and doctoral degree from the Philadelphia College of Pharmacy at the University of the Sciences in Philadelphia. He completed a M.S. degree at the University of Wisconsin-Madison, and training at the University of Wisconsin Hospital and Clinics. His primary interests include medication safety, clinical decision support, and the clinical implementation of pharmacogenetics.
PG4KDS: A model for the clinical implementation of pre-emptive pharmacogenetics
Article first published online: 11 MAR 2014
© 2014 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Special Issue: Implementation of Genomic Medicine
Volume 166, Issue 1, pages 45–55, March 2014
How to Cite
2014. PG4KDS: A model for the clinical implementation of pre-emptive pharmacogenetics. Am J Med Genet Part C Semin Med Genet 166C:45–55., , , , , , , , , , , , , .
Conflict of Interest: Dr. Mary V. Relling and Dr. William E. Evans receive royalties from licensing TPMT genotyping, Prometheus Labs.
* Correspondence to: James M. Hoffman, St. Jude Children's Research Hospital, Pharmaceutical Sciences Department, 262 Danny Thomas Place MS #150, Memphis, TN 38105. E-mail: firstname.lastname@example.org
- Issue published online: 18 MAR 2014
- Article first published online: 11 MAR 2014
- NCI. Grant Numbers: CA 36401, CA 21765
- NIH/NIGMS Pharmacogenomics Research Network. Grant Numbers: U01 GM92666, UO1 HL105918
- The American Lebanese Syrian Associated Charities (ALSAC)
- electronic health record;
- clinical decision support;
- personalized medicine
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.