PG4KDS: A model for the clinical implementation of pre-emptive pharmacogenetics

Authors

  • James M. Hoffman,

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    • 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.
  • Cyrine E. Haidar,

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    • Cyrine E. Haidar, Pharm.D., B.C.P.S., B.C.O.P. is the Clinical Pharmacogenetics Coordinator at St. Jude Children's Research Hospital. She is also an assistant professor at the University of Tennessee College of Pharmacy. Dr. Haidar earned both her B.S. in pharmacy and her Pharm.D. degrees from the Lebanese American University. She completed a pharmacy practice residency at Hackensack University Medical Center and a pediatric oncology specialty residency at St. Jude Children's Research Hospital. Her research interests include the clinical implementation of pharmacogenetics.
  • Mark R. Wilkinson,

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    • Mark R. Wilkinson, B.S., is a senior research database analyst in the Department of Pharmaceutical Sciences at St. Jude Children's Research Hospital. He serves as the lead analyst for software application and database development, data analysis, and data quality control for departmental initiatives.
  • Kristine R. Crews,

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    • Kristine R. Crews, Pharm.D., B.C.P.S. is Translational Research Laboratory Director in the Pharmaceutical Sciences department at St. Jude Children's Research Hospital and is Director of the first ASHP-Accredited PGY2 Residency in Clinical Pharmacogenetics. Dr. Crews earned both her B.S. in pharmacy and her Pharm.D. degrees from Rutgers University. She completed a pharmacy practice residency and a clinical pharmacokinetics specialty residency at the University of Kentucky Chandler Medical Center and completed a fellowship in clinical pharmacokinetics and pharmacodynamics at the University of North Carolina and Glaxo Wellcome, Inc. Her research interests include the clinical implementation of pharmacogenetics to individualize treatment regimens for children with cancer.
  • Donald K. Baker,

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    • Donald K. Baker, Pharm.D., M.B.A. is the Clinical Decision Support Officer in the Information Sciences Department at St. Jude Children's Research Hospital. He is responsible for the development and optimization of all the custom and vendor supplied clinical decision support in the St. Jude electronic health record. He earned his Pharm.D. at the University of Tennessee and an M.B.A. at the University of Memphis.
  • Nancy M. Kornegay,

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    • Nancy Kornegay, M.B.A., is a senior database administrator at St. Jude Children's Research Hospital. She is responsible for the archival storage and management of all sampling, drug dosing, clinical, and research pharmacokinetic and laboratory data for the Pharmaceutical Sciences Department.
  • Wenjian Yang,

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    • Wenjian Yang, Ph.D., is a bioinformatics analyst and developer at St. Jude Children's Research Hospital. He obtained Ph.D. in statistics at University of Memphis. His research interests include discovering genetic predictors in treatment and biology of leukemia.
  • Ching-Hon Pui,

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    • Ching-Hon Pui, M.D., is the Chair of the Department of Oncology at St. Jude Children's Research Hospital, the co-leader of the Hematological Malignancies Program at St. Jude Cancer Center, and an American Cancer Society Professor. His primary research interest is in the biologic study and treatment of childhood leukemias. He translates laboratory discoveries to the development of “Total Therapies” for children with leukemia.
  • Ulrike M. Reiss,

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    • Ulrike M. Reiss, M.D., is the Director of the division of Clinical Hematology and Director of the Hemophilia Treatment Center at St. Jude Children's Research Hospital. She is an associate faculty member at St. Jude. She trained at the University of Heidelberg and the Children's Hospital in Oakland, California. Her clinical research focuses on bleeding disorders, thrombosis, and bone marrow failure syndromes.
  • Aditya H. Gaur,

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    • Aditya H. Gaur, M.D., is an associate faculty member in the Department of Infectious Diseases at St. Jude Children's Research Hospital in Memphis, TN. He obtained his pediatric training at the South Gujarat University in Surat, Gujarat, India, and pediatric infectious disease training at St. Jude Children's Research Hospital. His primary clinical interests are in Pediatric HIV infection, diagnosis and treatment of infections in immunocompromised children as well as the epidemiology of infectious diseases.
  • Scott C. Howard,

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    • Scott C. Howard, M.D., M.S., a full member in the Leukemia/Lymphoma division at St. Jude Children's Research Hospital. He is the director of Outcome Evaluation and the Morocco Programs for St. Jude's International Outreach Program, and a professor at the University of Tennessee College of Medicine. His primary interests are in translating state-of-the-art pediatric cancer treatments to countries with limited resources, and treatment and research for children with Hodgkin lymphoma and acute lymphoblastic leukemia.
  • William E. Evans,

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    • William E. Evans, Pharm.D., is the director and chief executive officer at St. Jude Children's Research Hospital, he holds the Donald Pinkel Chair of Childhood Cancer Treatment at St. Jude and is a Professor of Pediatrics and Pharmacy at the University of Tennessee Colleges of Medicine and Pharmacy. He trained at the University of Tennessee. His primary interests are focused on the pharmacogenomics of anticancer agents in children with an emphasis on childhood acute lymphoblastic leukemia.
  • Ulrich Broeckel,

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    • Ulrich Broeckel, M.D., is Professor of Pediatrics, Medicine and Physiology and the Section Chief of Genomic Pediatrics at the Medical College of Wisconsin and the Children's Research Institute. He graduated from the University of Heidelberg, and trained at the University of Regensburg Germany and the Medical College of Wisconsin where he completed his post-doctoral fellowship in physiology and genetics. His primary research interests are genetics of complex diseases and the application of genetics and genomics in clinical care.
  • Mary V. Relling

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    • Mary V. Relling, Pharm.D., is the chair of the Department of Pharmaceutical Sciences at St. Jude Children's Research Hospital. She is one of the principal investigators within NIH's Pharmacogenomics Research Network and co-founder of CPIC, the Clinical Pharmacogenetics Implementation Consortium. She is also a professor at the University of Tennessee in the Colleges of Medicine and Pharmacy. She earned her undergraduate B.S. degree from the University of Arizona College of Pharmacy and her doctoral degree from the University of Utah College of Pharmacy. Her primary interests are in treatment of childhood leukemia and clinical implementation of pharmacogenetics.

  • 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: james.hoffman@stjude.org

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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