Editors' ChoicePHARMACOGENETICS

PREDICTing the Era of Personalized Medicine

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Science Translational Medicine  05 Feb 2014:
Vol. 6, Issue 222, pp. 222ec26
DOI: 10.1126/scitranslmed.3008567

Delivering the right dose of the right drug to the right individual at the right time is an often stated goal of the pharmacogenomics community. Over the past decade, the role of common genetic variation in a handful of key pharmacogenes has been elucidated. These genetic variants have been associated with variable responses to routinely used medications, such as clopidogrel and warfarin. In addition, for each of these variants, there are clear alternatives on the basis of the genetic test results—for example, adjust the dose. Although many encourage the use of genetic tests in medication decision-making, there is no optimal model for incorporating pharmacogenetic testing into routine clinical care, including whom to test and whether testing should be preemptive (before drug prescription) or reactive (after drug prescription). A study by Van Driest et al. makes great strides in providing a path forward.

The Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment (PREDICT) program at Vanderbilt performed preemptive pharmacogenetic testing using a panel of gene variants affecting the metabolism of five candidate medications since 2010. Patients were referred to the program on the basis of a specific indication (coronary stenting or diagnosis of leukemia) or an algorithm that predicted the use of one of the drugs of interest within the next 3 years. Enrolled patients were tested for 184 genetic variants in 34 genes. Since 2010, 10,000 patients have been preemptively tested through PREDICT, and in this study, Van Driest et al. report the results with respect to five selected drugs. The authors showed that 90% of patients carried at least one actionable genetic variant. Further, more than 40% of European Americans and nearly 20% of African Americans carried an actionable variant and were exposed to one of the medications of interest. Lastly, the authors demonstrated that patients on multiple drugs would benefit from testing multiple variants at once instead of sequentially, thus reducing the total number of tests being ordered.

These are early times in implementing genetic findings into routine clinical care; however, pharmacogenetics represents the “low-hanging fruit” in this emerging field. The work by the PREDICT investigators represents a major advance in how to implement pharmacogenetic testing in routine clinical care. The lessons learned will likely set an example for a future when actionable genetic variants are incorporated across a wide variety of diseases—not just for drugs. As a consequence, we are closer to personalized drug therapy and improved patient outcomes.

S. Van Driest et al., Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clin. Pharmacol. Ther., published online 22 January 2014 (10.1038/clpt.2013.229). [Abstract]

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