stanford medicine



Slow on the uptakeA gene test speeds accurate dosing of a dangerous drug — but few use it

About 2 million people in the United States each year are prescribed warfarin, a blood-thinning drug, to prevent clotting after having a stroke or a heart attack. But to be used safely, the drug dose has to be precisely calibrated: Too much can cause life-threatening bleeding. The standard dosing approach for the drug (commonly marketed as Coumadin) has been to start low and inch up, with frequent blood tests to determine when the proper concentration is reached, a process that takes weeks to months.

Terry Allen
William Kuo

Recent advances in genetic testing, however, have made it possible to quickly and (relatively) inexpensively test each patient’s DNA to determine an optimal starting dose, resulting in an adjustment period that’s less lengthy and less hazardous. In January, the Food and Drug Administration added gene-based dosing information to the label, and in March, Medco Health Solutions Inc. — one of the largest managers of drug benefits in this country — began encouraging doctors and patients to use the genetic test, which costs about $200.

 It sounds like a no-brainer. Why wouldn’t doctors use the test to keep their patients safer? Turns out, there are a lot of reasons.

“Physicians have not been trained to use genetics when making drug-prescribing decisions,” says Russ Altman, MD, PhD, professor of bioengineering, genetics and medicine at Stanford’s School of Medicine, “so this is a big change in their work flow. We need to educate them and build a health information infrastructure to fully deliver the promise of modern genomic medicine.” Less than 1 percent of physicians who prescribe warfarin use the test to determine their patients’ starting doses, Altman estimates.

Altman and senior researcher Teri Klein, PhD, led a group of collaborators in a 2009 study that correlated variations in two genes with a patient’s optimum warfarin dose. Together they designed a computerized algorithm to predict an appropriate starting dose based on genetic, demographic and clinical information about each patient.

But education and infrastructure aren’t the only issues for physicians: They’re just not all that convinced it’s necessary. “It’s all about cost, efficiency and value,” says Edward Abrahams, PhD, president of the nonprofit education and advocacy-focused Personalized Medicine Coalition. “Until those questions are answered, it’s difficult to institute change in medicine, which is a notoriously conservative field.” It’s not just individual physicians who need convincing. In 2009, the Centers for Medicare and Medicaid Services decided not to cover the genetic test. That is, unless the patients were enrolled in a prospective, randomized clinical trial to determine the effectiveness of such an approach.

Clinical trials are under way, with preliminary results expected at the end of this year. If they show that patients are less likely to be hospitalized or suffer complications, the tide might begin to shift, with some caveats.

“There are two groups of people,” says Caroline Berube, MD, medical director of Stanford’s Oral Anticoagulation Clinic. “Some really believe in and are pushing for the test. Others argue that even though dosing is more predictable with the test, more than half the variation in dose response among patients remains unexplained by genetics. But if the trials show clinical benefit, if the cost of the test comes down and if we can order and have access to the results within 24 hours, I think physicians will start to use it.”

Krista Conger






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