February 16, 2012

VUMC pilot clinics launch genotyping for drug safety

by Paul Govern

Vanderbilt University Medical Center is building a highway to personalized medicine, and the section of road currently under construction involves spreading the word among providers in pilot clinics, including Cardiology, Diabetes and Primary Care, about prospective genetic testing for certain patients.

When a drug doesn’t work for a patient, or when a patient experiences side effects but receives no benefit, that’s considered an adverse drug reaction.

Certain common genetic variants, or genotypes, have been found to change the odds for certain drug responses. With the explosion of genomics, more of these so-called gene-drug interactions are coming to light.

Personalized medicine in part will mean checking genotypes to ensure patients get the right drug at the right dose from the very start.
Across the health care system today, when clinical genotyping is done at all, it's typically limited to a single gene-drug interaction.

Using a more farsighted approach, Vanderbilt is mounting prospective, wide-spectrum genotyping. A single test, variously known as a PREDICT or PDX test, looks at 184 common genetic variants (single-nucleotide polymorphisms) collectively implicated in a host of known and suspected gene-drug interactions.

“This isn’t about any one medicine. It’s about showing that, by testing prospectively, we can avoid a range of therapeutic delays and mishaps,” said Jim Jirjis, M.D., MBA, assistant chief medical officer and the physician lead for implementation of PREDICT (Pharmacogenomic Resource for Enhanced Decisions in Care and Treatment).

The verdict isn’t in regarding clinical implications of most of the genotypes covered by the PREDICT/PDX test. Use of the test is being phased in by the Pharmacy and Therapeutics Committee as evidence builds.

As gene-drug interactions are reported in the research literature and noted in drug labeling, the committee decides whether to list them for clinical testing.

“To deliver personalized medicine, we’re using a systems-based approach that sets Vanderbilt apart from other centers,” said Dan Roden, M.D., assistant vice chancellor for Personalized Medicine, who oversees PREDICT.

“It’s likely that, in the not-too-distant future we’ll all be genotyped for drug safety. In the meantime, we’re using this multi-gene approach, along with informatics models to identify patients who are likely to receive culprit drugs. We’re prompting providers to get those patients tested.”

The gene-drug interactions currently listed for testing involve the cholesterol lowering drug simvastatin (Zocor) and the anti-clotting drug clopidogrel (Plavix). The pilot clinics see many patients who take these drugs.

Other gene-drug interactions now being considered for testing involve the anticoagulant warfarin, the cancer drug tamoxifen, and two immunosuppressives, azathioprine and tacrolimus.

Part of what distinguishes personalized medicine at VUMC is that, under PREDICT, a computer program scans electronic records to forecast each patient’s risk, over a three-year horizon, of receiving listed drugs. When the risk surpasses a threshold, the patient’s provider receives an automated alert through StarPanel (Vanderbilt’s electronic medical records application) suggesting a PREDICT/PDX order.

The StarPanel patient summary displays the results — but only those that concern listed drugs. The remaining results are stored for later use as more drugs become listed for testing by the Pharmacy and Therapeutics Committee.

With test results available, as providers write electronic prescriptions for listed drugs, an alert will be issued if the genotype suggests an alternate dose or drug.

For now, Vanderbilt provides PREDICT/PDX at no cost to patients. Approximately 4,300 patients have been tested and Jirjis expects another 6,000 to be tested by June.

The program manager for PREDICT is Jennifer Mitchell, MSN, of the VMG I2 Team. The informatics analyst is Marc Beller, of the Informatics Center.

For more information providers can call 875-4363 (875-GENE). Patients can call 343-9188, or toll-free, (866)-886-2478.