Pharmacogenomic testing: Relevance in medical practice
ABSTRACTGenetics may account for much of the variability in our patients’ responses to drug therapies. This article offers the clinician an up-to-date overview of pharmacogenomic testing, discussing implications and limitations of emerging validated tests relevant to the use of warfarin (Coumadin), clopidogrel (Plavix), statins, tamoxifen (Nolvadex), codeine, and psychotropic drugs. It also discusses the future role of pharmacogenomic testing in medicine.
KEY POINTS
- Polymorphisms that affect the pharmacokinetics and pharmacodynamics of specific drugs are common.
- Testing for certain polymorphisms before prescribing certain drugs could help avoid adverse drug effects and improve efficacy.
- Pharmacogenomic testing has only recently begun to enter clinical practice, and routine testing is currently limited to a few clinical scenarios. However, additional applications may be just around the corner.
- Many pharmacogenomic tests are available, but testing has not yet been recommended for most drugs. Needed are large-scale trials to show that routine testing improves patient outcomes.
THE FUTURE OF PHARMACOGENOMIC TESTING
The examples discussed in this article provide some insight about how pharmacogenomic testing is maturing and slowly being integrated into the practice of medicine. They also illustrate the complexity of the multiple stages of research that pharmacogenomic applications must go through in order to be adopted as standard practice.
In the future, pharmacogenomic data will continue to accumulate, and the clinical utility of many other pharmacogenomic tests may be uncovered. The FDA provides information on emerging pharmacogenomic tests at its Web site, www.fda.gov.11 Its up-to-date “Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels” includes boxed warnings, recommendations, research outcomes, and relevant population genetics.
If the FDA continues its current policy, prospective randomized trials that show improvement in patient outcomes will remain the gold standard for determining the clinical significance of a pharmacogenomic test. Furthermore, cost-benefit analyses are likely to continue dictating policy regarding pharmacogenomic testing, and cost-benefit profiles should improve as technology advances and as information gathered from a single test becomes applicable to multiple medications and clinical scenarios.
In the meantime, physicians should become familiar with the terms used in medical genetics and pharmacogenomics and begin to understand genetic contributions to the outcomes of drug therapy. For example, understanding the consequences of metabolizer status and the frequency of variants in a given population can be tremendously helpful when advising our patients about anticipating potential problems when taking specific medications and about making informed decisions about pharmacogenomic testing.
This exchange of information alone may go a long way in improving therapy outcomes even when prospective pharmacogenomic testing is not routinely performed. Furthermore, an increasing number of patients will already have genotyping information available when they come to us, and clinicians need to be aware of the many pharmacogenomic applications recommended by the FDA when genetic status is known.10
