{'fraction_non_alphanumeric': 0.02899884925201381, 'fraction_numerical': 0.006214039125431531, 'mean_word_length': 5.353801169590644, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Getting Pharmacogenomics Into the Clinic.

What if there were a way to know if a depressed patient would respond to an antidepressant— before it was prescribed? Or to predict a bleeding event from an antiplatelet therapy? In recent years, advances in genetic testing have made such drug-response predictions possible for patients with certain gene variants. But physician adoption is moving slowly, say experts in the growing field of pharmacogenomics. “While we’ve made tremendous rapid advances in terms of basic science and technological advances, and [while] clinical outcomes [are] there for some gene-drug pairs, clinical implementation unfortunately has been lagging behind,” said Edith A. Nutescu, PharmD, MS CTS, associate professor and director of the Center for Pharmacoepidemiology and Pharmacoeconomic Research at the University of Illinois at Chicago College of Pharmacy. In the results of a nationwide survey by the American Medical Association released in 2012, only 13% of more than 10 000 responding physicians had ordered a pharmacogenomic test in the previous 6 months, although almost all of them—98%—agreed that drug responses may be influenced by genetic variations. Genotype-guided prescribing—also referred to as pharmacogenetics, or PGx—is expected to become routine as genetic profiling becomes more commonplace. “[I]t is likely that a time will come in the near future where patients will start to demand the use of such information during care—that they will ask of their physician, ‘Have you considered my genomics?’ before accepting a prescription,” said Peter H. O’Donnell, MD, associate director for clinical implementation at the University of Chicago’s Center for Personalized Therapeutics. In the meantime, major efforts are under way to prove that pharmacogenomic tests have clinical utility and to make it easier for physicians to choose these tests and interpret and act on the results, translating them into better outcomes for their patients. How Does Pharmacogenomics Work? “Genetic variability affects essentially every single gene in the human genome and sometimes it’s going to affect genes whose proteins are critical for drug response,” said Mary V. Relling, PharmD, chair of the pharmaceutical sciences department at St Jude Children’s Research Hospital. Most so-called pharmacogenes encode drug-metabolizing enzymes, and each individual’s genotype for a particular gene can be categorized into 1 of 5 phenotypes that describe the enzyme’s activity— ultrarapid metabolizer, rapid metabolizer, normal metabolizer, intermediate metabolizer, and poor metabolizer—Nutescu explained. Other genes encode the enzymes that are the site of action where drugs exert their effects; patients with variations in these genes may be more sensitive or resistant to certain drugs than normal. Knowing this information can help clinicians choose the right medication or dose for a patient. A patient who has a genetic variant associated with slow metabolism of the drug thinner warfarin, for example, might experience major bleeding on a standard dose. In contrast, a patient with a variant associated with fast warfarin metabolism might not get any benefit from the standard dose, putting them at greater risk of a major stroke or thromboembolism. “Warfarin is consistently among the top 10 medications that leads to hospitalizations due to adverse events,” Nutescu said. “Drugs that are more prone to side effects, complications, hospitalizations, [and] resource use, clearly should be on the radar.” By screening for variants in the 2 genes that influence warfarin metabolism and sensitivity, CYP2C9 and VKORC1, respectively, a physician can adjust the dose to optimize treatment and prevent an adverse event. “The goal is to avoid trial and error, to make patients safer, and to increase the chance for effectiveness when they start a medication,” O’Donnell said. Advocates of pharmacogenomics say the field is an emerging resource for improving patient safety. Since 2012, more than 1 million adverse drug events have been reported each year to the US Food and Drug Administration (FDA), “many of which might be preventable using PGx testing,” Geoffrey S. Ginsburg, MD, PhD, director of the Center for Applied Genomics and Precision Medicine at Duke University Medical Center, said in an email. News & Analysis