Warfarin is a very challenging drug to prescribe and manage. Not only is the therapeutic window narrow, but achieving the correct dose and maintaining a stable international normalized ratio (INR) for patients can be problematic. Any reasonably cost- and time-effective improvement in warfarin management would be welcomed by most clinicians.
Over the last several years new genetic tests for variants in the CYP2C9 and VKORC1 genes have been developed that predict a substantial component of warfarin metabolism. Many scientists and academic health care providers feel that prospective use of these tests may save lives and health care resources. To date, several small studies comparing the use of genetic testing to standard of care have produced mixed results. There may be evidence for reduced use of blood draws for INRs and office visits, but no large trial has demonstrated a mortality benefit. The FDA has altered warfarin's labeling to reflect this new information.
A number of companies and health care systems already have geared up to offer warfarin pharmacogenetic tests with a rapid turn-around time. The National Heart, Lung and Blood Institute of the National Institutes of Health started a major trial of warfarin pharmacogenetic testing through the University of Pennsylvania, which should greatly enhance our understanding of the clinical utility of such tests.
Interestingly, the Centers for Medicare and Medicaid Services opened a National Coverage Analysis (NCA) of the topic. The public comment for this NCA runs until Sept. 3. For some in the personalized medicine community, this NCA is viewed as a critical test case of personalized medicine predicated on genomic information. Perhaps this overstates the situation. It probably is best viewed as an opportunity for a much-needed dialogue between supporters of personalized medicine and evidence-based medicine.
Will the nation's largest health care payer accept the current evidence supporting the use of warfarin pharmacogenetic testing in routine care? A recent review using the Rapid ACCE format by McClain et al. raised serious concerns regarding gaps in the current evidence base. However, this is a rapidly moving field and more data are now available.
In a time of rapid advances in genetics and genomics and spiraling health care costs, any significant "evidentiary gap" will be increasingly problematic for promising and potentially very significant improvements in standard of care. Substantial resources should be directed at re-tooling our research and health care delivery systems to rapidly and responsibly generate the types of effectiveness data needed to separate the wheat from the chaff in genomics, and more broadly, all emerging health care technologies.
W. Gregory Feero, MD, PhD, a family physician with a doctorate in human genetics, is senior adviser for genomic medicine in the Office of the Director at the NIH's National Human Genome Research Institute. His column runs every issue in ACP Internist