Yet despite their availability, the tests have been slow to catch on in the clinic, comments Howard McLeod, a professor of medicine at Washington University. They, too, require a lot more validation, even though the basic biology is known. Although many studies have shown the relationship between CYP450 genes and specific drugs, very few have actually correlated the relationship with dosing guidelines that physicians can use, McLeod explains. What's more, because these drugs are long-time staples of clinical practice, physicians are used to the trial-and-error approach for prescribing them. "We really have to prove that making decisions with the test is better than making decisions without it," he says.
But conducting the prospective studies to establish that dosing is gene-dependent "takes a lot of effort, a lot of time and a lot of money," McLeod reflects, and big pharma has not been particularly motivated to fund them. "There's no sugar-daddy for 40-year-old drugs." Although the FDA can demand such studies for new drugs and diagnostics, it is powerless to ask companies to conduct more safety studies when a new technology becomes available.
Still, observes Roland Valdes, professor of clinical chemistry at the University of Louisville, there¿s enough data to start educating physicians on how to incorporate pharmacogenomic testing in their practice. "In all cases, you start by using the tests, and then match that up with the studies. If you wait for the studies it will never happen." In some clinical areas testing is gradually gaining acceptance. Psychiatrists, for example, are particularly interested, not just because up to 80 percent of psychiatric medicines are metabolized by CYP450 genes, "but also because there are some guidelines emerging for what you do about it" as researchers conduct more trials, McLeod remarks.
Reframing medicine to include pharmacogenomics will take some time, and experts note that the process will not always be pretty. "I hate to say it, but one of the biggest friends of pharmacogenomics [will be] litigation attorneys," McLeod warns. "Realizing that there are tests to predict toxicity--that's low-hanging fruit." But the benefits--not only for patient safety, but also for drug company profits--are only getting clearer. "I think companies are going to be encouraged to do this," Gene Logic's Mendrick predicts, recalling the flurry of problems with drug safety over the past year. "Think of Vioxx-- they could have saved that compound if they could tell which people would really be helped."