The National Heart, Lung, and Blood Institute is set to launch a 1,200-patient trial in March to investigate whether adjusting the dosing of the anticoagulant warfarin based on an individual patient’s genetic make-up is clinically useful. The trial will compare clinical outcomes of one group of patients given warfarin based on just clinical factors, and another group that is administered the drug based on clinical factors and genotype.

 

Warfarin is a widely prescribed to help prevent formation of blood clots in individuals who are at risk for thrombosis. Adverse side effects include severe bleeding. Warfarin also interacts with many commonly used drugs and its metabolism varies among patients, requiring close monitoring.

 

In August 2007, the FDA updated the label for warfarin to note that people with certain genetic variations may respond adversely to the drug. The decision was hailed as a validation of the concept of personalized medicine by encouraging physicians to tailor the prescription to the individual. However, the agency did not require physicians to genetically test their patients, noting that additional studies would be necessary to validate such a requirement. This has kept many large insurers from covering the cost of pharmacogenetic diagnostic tests to determine optimal dosing and the Centers for Medicare and Medicaid Services is currently in the process of making a national coverage decision on the technology. This new prospective study should help clear the air.

 

“The NIH research is precisely what is needed to advance the promise of personalized medicine, ensuring that patients receive the safest and most effective drug dose,” said Frank Torti, acting commissioner of Food and Drugs, in a statement.

 

The prospective, randomized-controlled study comes just after results of a large retrospective study conducted the International Warfarin Pharmacogenetics Consortium was published in last week’s New England Journal of Medicine. That study of clinical and genetic data from 4,043 patients concluded that when genetic information is factored in, the initial warfarin dose was much closer to the required stable therapeutic warfarin dose than when using just clinical factors or giving a fixed dose. It also found that pharmacogenetic-based warfarin dosing tended to benefit the 46.2 percent of patients at either end of the sample population, the “outliers,” who required the smallest and largest warfarin doses.

 

In an accompanying editorial in the same issue of New England Journal of Medicine written by Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, and Lawrence Lesko, director of the FDA’s Office of Clinical Pharmacology at the two officials noted that they were not surprised that the majority of patients in the middle range did not benefit from pharmacogenetic testing. They concluded that, “Pharmacogenetics has the potential to increase benefit and reduce harm in people whose drug responses are not ‘average.’”

 

“In some cases, randomized, controlled trials will be needed to determine whether pharmacogenetic testing is worthwhile; in others, less rigorous approaches will suffice,” they say. “Given the expected volume of genetic information and the relative paucity of randomized, controlled trials involving marketed drugs, we need clear thinking about what is required for the adoption of pharmacogenetic testing.”