Trend Toward Pharmacogenomics Means Challenges Ahead for Managed Care

Atlanta—The increasing trend toward personalized medicine means managed care must use an “adopt when appropriate” approach rather than one of “adopt everything for everyone,” according to information presented at the AMCP meeting by Laurie Amirpoor, PharmD, of WellPoint, Inc, and Lawrence J. Lesko, PhD, FCP, of the Center for Pharmacometrics and Systems Pharmacology, University of Florida in Lake Nona. Both presenters discussed the many issues surrounding pharmacogenomics that managed care plans must take into account in a Contemporary Issues session titled Pharmacogenomics—Applications for Managed Care. Personalized medicine refers to the use of genetic or other molecular biomarker information obtained through pharmacogenomics to improve the safety, effectiveness, and health outcomes of patients. Individual genetic information, combined with other patient information, allow physicians to uncover a patient’s susceptibility to a disease, more accurately predict prognosis, identify responders and nonresponders to a drug, identify those at risk for adverse drug reactions, and guide dose selection to improve outcomes. Dr. Amirpoor cited the HER2/neu test that is used to determine the appropriateness of Herceptin (trastuzumab) therapy in breast cancer, and KRAS/EGFR testing for Vectibix (panitumumab) in the treatment of colorectal cancer, as some current examples of pharmacogenomics. The anticipated benefits of pharmacogenomics are many but there are barriers to its progress, as well The considerations for managed care that pharmacogenomics present are numerous, and cover the appropriate use of personalized medicine, ethics, compliance, and affordability. Appropriate use is a top concern, and it is unclear if US Food and Drug Administration (FDA) approval of a particular drug would require genetic testing. Most in vitro diagnostic tests are not FDA approved, and these tests can vary greatly in complexity and costs. Evidence-based data are needed to demonstrate the efficacy and safety of the drug, and providers need to have the necessary knowledge to interpret and apply diagnostic test results. Ethics is another issue, as coverage decisions may be impacted by false-positive or false-negative results, and medical privacy is possibly put at risk; will results of diagnostic testing affect an individual’s employment status, life insurance eligibility, or access to therapy in the future? Additionally, if no other treatment options are available, what may happen to a patient if the diagnostic test results do not support use of the drug? Compliance. It is unknown if state/federal mandates will require health plans to cover specific drug classes regardless of genetic testing results. Legislative mandates can increase the cost of monthly premiums from <0.1% to >5%. Health plan decision makers will need to know how reliable genetic testing is and whether test results actually help members improve their overall health and quality of life. Affordability. Interventions that produce 1 quality-adjusted life-year (QALY) for <$50,000 is considered cost-effective; those that cost between $50,000 and $100,000 are thought to be questionable; and >$100,000 per QALY are deemed not cost-effective. Health plan decision makers must determine the implications of genetic testing on healthcare costs. Issues related to affordability that must be considered, Dr. Amirpoor indicated, are whether diagnostic testing results need to be extended to a patient’s family members, and what the value of testing is if a drug must be covered regardless of the test results. Several factors influence the cost-effectiveness of genetic testing: • Prevalence of genetic mutation and disease in population • Severity and cost of the disease or outcome the test is designed to predict or diagnose • Strength of the association between the genetic mutation and clinical outcomes • Availability of effective interventions that can be implemented on the basis of genetic information and that provide a reduction in the relevant event rate compared with standard care • Whether testing is for prediction of future risk or for immediate diagnostic or prescribing decisions • Cost, turnaround time, and accuracy of the test and whether the results provide information for a single condition or multiple conditions • The cost of counseling, if relevant • The potential downstream and indirect costs and benefits, such as the extent to which family members are tested, the potential ramifications of loss of privacy if genetic results are disclosed, etc. Dr. Lesko discussed 2 specific examples of pharmacogenomics. Abacavir is an antiviral medication used to treat HIV-1 that was discovered to cause serious hypersensitivity reactions in 8% of patients. Genetic variations in human leukocyte antigen were found to be a predictor of these reactions, particularly HLA-B*5701. Ultimately, the FDA updated the labeling for abacavir to reflect a warning to patients having the HLA-B*5701 allele. In the case of abacavir, screening for this allele is considered medically necessary before beginning a patient on abacavir therapy. Warfarin, an anticoagulant used to treat thromboembolic disorders, has been available for >50 years, is an inexpensive drug, but is associated with high rates of adverse drug reactions. Genetic variations in human CYP 2C9 and VKORC1 were found to affect the intensity of anticoagulation and steady-state doses in patients. Results of a study showed patients who were genotyped had a 33% lower rate of hospitalization for any cause and a 44% lower rate of bleeding or thromboembolism compared with a control group. A study of Medco data showed genotyping for warfarin to be slightly cost-effective to cost-neutral. As with abacavir, the FDA updated the labeling for warfarin; however, unlike abacavir, the clinical value of genotyping for warfarin is still considered to be experimental and investigational.