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. doi: 10.1002/ajmg.c.31391. Epub 2014 Mar 11.


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.

Keywords: clinical decision support; electronic health record; personalized medicine; pharmacogenetics; pharmacogenomics.

MeSH terms

  • Aryl Hydrocarbon Hydroxylases / genetics
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6 / genetics
  • Electronic Health Records
  • Gene Dosage
  • Genetic Testing / methods*
  • Genotype
  • Humans
  • Liver-Specific Organic Anion Transporter 1
  • Medical Informatics Applications*
  • Methyltransferases / genetics
  • Models, Theoretical*
  • Organic Anion Transporters / genetics
  • Pharmacogenetics / methods*
  • Pharmacogenetics / trends
  • Practice Patterns, Physicians'*
  • Protein Array Analysis


  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2D6
  • Methyltransferases
  • thiopurine methyltransferase