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In recent years, DNA variants in two different genes have been linked to how much blood thinner a patient needs. Researchers have developed algorithms to predict a proper dose based on those genes as well characteristics such as weight and age. But now new research suggests these formulas may not actually help doctors determine the right dose.

Blood thinners can be difficult to prescribe because each patient can respond differently depending on their physical characteristics, their diet, and other medications they take. Based on that information, doctors tailor the dosage so it is high enough to prevent clotting but not so high that it causes internal bleeding. Once an initial dose is given, blood tests can help a doctor tune in to the best dose.

The hope has been that doctors might be better able to hit the right dose by looking at genes known to affect a patient’s response to the drugs—an approach called pharmacogenetics. Many experts have promoted this approach and some small patient trials have offered hope, writes Bruce Furie, a Harvard specialist in bleeding and clotting disorders, in an editorial in the New England Journal of Medicine. The U.S. Food and Drug Administration even changed the label of one blood thinner to note the effects of these gene variants. The genetics of blood-thinner response is also often used as an example of how genome analysis could be medically useful (see “Why We Have a Right to Consumer Genetics”).

But others have resisted the push to incorporate gene testing into blood-thinner prescription because there haven’t been large-enough trials to prove that it makes a difference in finding that right dose for patients (see “Enhancing Access to Genomic Medicine”). Three studies published on Tuesday in the NEJM suggest that this cautious take may be right.

Two of the studies found that gene testing made no difference in how well a doctor could find the right dose. The third found that genetic testing offers only a small improvement: patients were on the right amount only seven percent more often if gene testing was incorporated into their dosing. And one of studies found that genetic analysis even misguided dosing for African American patients.  

A caveat to the negative conclusions of these studies is that some of the patients did not have genetic data available before their first dose. In these cases, genetic information became available a few days after their first dose and was used in combination with standard assessments to adjust the dosing.

So what does it mean that this poster child of pharmacogenetics should fare so poorly in large trials? The National Institutes of Health, which funded one of the studies, doesn’t think that it’s time to give up on the idea that genetic tests could help inform drug decisions, but says that these ideas need the same testing as other medical treatment strategies:

“These findings highlight the importance of developing and evaluating pharmacogenetic testing in patients from diverse racial and ethnic backgrounds,” [said Gary Gibbons, director of the National Heart, Lung and Blood Institute at the NIH in a released statement.] “We are optimistic about the prospects of personalized, precision medicine, but we must make sure that we put these approaches through the same type of rigorous testing as any other prognostic test or clinical treatment strategy.”

But even if genetic testing is shown contribute to some drug-use decisions, will the costs of the new technology be worth the medical improvements? In the study that did find a small improvement in dosing for patients given genetic tests, the gain was so small that some experts say it is outweighed by the added costs and effort for clinics to perform these tests.

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