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Getting Personal

Genetic testing guides prescriptions

By Bill Snyder
August 2012

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Since it was launched two years ago, a clinical decision-support program developed at Vanderbilt University Medical Center has tested more than 7,800 patients for genetic variations that affect responses to several commonly prescribed drugs.

Genetic variations affecting the anti-platelet drug clopidogrel (Plavix) and the cholesterol-lowering drug simvastatin (Zocor) currently are reported in patients’ electronic health records, and doctors are notified if they prescribe either drug to patients with known genetic variants.

During the next year, variations that affect responses to several other drugs, including the anti-coagulant warfarin, will be added to electronic health records under the program, called PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment).

While the impact of the program on clinical outcomes is not yet known, Josh Peterson, M.D., MPH, assistant professor of Medicine and Biomedical Informatics, estimated that genetic testing conducted to date has helped avoid severe gene-drug interactions in hundreds of patients.

A much larger data set will be required to “convince us and the rest of the world that this is the way to prescribe medicine,” said Dan Roden, M.D., assistant vice chancellor for Personalized Medicine, during a “PREDICT Town Hall” held at the Medical Center in June.

The program’s potential value is huge, said Joshua Denny, M.D., MS, assistant professor of Biomedical Informatics and Medicine. In a study of nearly 53,000 Vanderbilt outpatients, 65 percent had been prescribed drugs with known genetic interactions.

Using genetic testing to guide prescribing for these patients could avoid an estimated 383 severe adverse drug events over five years, he said.

In the case of clopidogrel, which is frequently given to prevent formation of blood clots after catheterization or stent procedures, about 20 percent of patients carry a specific genetic variation that prevents them from adequately responding to the drug. As a result, they’re at higher risk for heart attack or stroke.

In 2 percent of patients who carry another genetic variation, simvastatin is associated with an increased risk of muscle toxicity and possible kidney damage.

In both cases, giving physicians genetic information in advance can help them determine whether their patients should be prescribed a different dose or drug.

Vanderbilt is “well-positioned” to pioneer this new way of prescribing medicine, Roden said, because of its strong, 49-year-old Clinical Pharmacology program and major investments in biomedical informatics and genome science that have been made by the university since the 1980s.

In addition, Vanderbilt is the recipient of a Clinical and Translational Science Award (CTSA), which recently was renewed for another five years for $46 million. The award, from the National Center for Advancing Translational Sciences of the National Institutes of Health, is the university’s largest single government research grant.

The CTSA is administered by the Vanderbilt Institute for Clinical and Translational Research (VICTR), which, since the initial award in 2007, has built an efficient framework for conducting biomedical research in partnership with Nashville’s Meharry Medical College.

“The CTSA program has been a national experiment to improve the pace and efficiency of clinical and translational research across the country,” said Gordon Bernard, M.D., associate vice chancellor for Research and senior associate dean for Clinical Sciences. “We believe it has been successful.”

Through its contributions to PREDICT and to BioVU, Vanderbilt’s massive DNA databank, for example, VICTR has aided the university’s emergence as a major player in personalized medicine.


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