Pharmacogenomics and individualized medicine: translating science into practice

Abstract

Research on genes and medications has advanced our understanding of the genetic basis of individual drug responses. The aim of pharmacogenomics is to develop strategies for individualizing therapy for patients, in order to optimize outcome through knowledge of the variability of the human genome and its influence on drug response. Pharmacogenomics research is translational in nature and ranges from discovery of genotype-phenotype relationships to clinical trials that can provide proof of clinical impact. Advances in pharmacogenomics offer significant potential for subsequent clinical application in individual patients; however, the translation of pharmacogenomics research findings into clinical practice has been slow. Key components to successful clinical implementation of pharmacogenomics will include consistent interpretation of pharmacogenomics test results, availability of clinical guidelines for prescribing on the basis of test results, and knowledge-based decision support systems.

Figures

Figure 1

The pathway of pharmacogenomics, from science to implementation.

Figure 2

Steps involved in translating a genotype test result into therapy recommendations in a patient’s health record. Several well-characterized genes have variants which can be translated into likely star-allele (*) nomenclature and from there into diplotypes, or specific genetic variant combinations. Each diplotype is translated into a probable phenotype, which drives dosing recommendations for affected medications. The steps required vary based on whether the result is determined to be high-priority or routine, where high-priority refers to a result that has an actionable gene-based dosing recommendation. Dosing recommendations can be delivered to the clinician by static written pharmacogenomic consultations in the electronic medical record (EMR), and by decision-support based automated alerts which fire when an affected drug is ordered to a patient with an actionable pharmacogenomic test result. Patients are informed about each phenotype result and, if necessary, about recommended changes to therapy.