Tuesday, October 09, 2007

The Challenges Facing Pharmacogenomics

Sometimes the things we believe will help us (e.g. a drug) can have the opposite effect. One reason for this is that current medical practice is largely premised on a "one size fits all" mentality. But the rise of pharmacogenomics promises to help us bring about more safe and effective treatments. This NCBI website describes the potential benefits of pharmacogenomics:


Adverse Drug Reaction. These three simple words convey little of the horror of a severe negative reaction to a prescribed drug. But such negative reactions can nonetheless occur. A 1998 study of hospitalized patients published in the Journal of the American Medical Association reported that in 1994, adverse drug reactions accounted for more than 2.2 million serious cases and over 100,000 deaths, making adverse drug reactions (ADRs) one of the leading causes of hospitalization and death in the United States. Currently, there is no simple way to determine whether people will respond well, badly, or not at all to a medication; therefore, pharmaceutical companies are limited to developing drugs using a "one size fits all" system. This system allows for the development of drugs to which the "average" patient will respond. But, as the statistics above show, one size does NOT fit all, sometimes with devastating results. What is needed is a way to solve the problem of ADRs before they happen. The solution is in sight though, and it is called pharmacogenomics.

What Is Pharmacogenomics?

The way a person responds to a drug (this includes both positive and negative reactions) is a complex trait that is influenced by many different genes. Without knowing all of the genes involved in drug response, scientists have found it difficult to develop genetic tests that could predict a person's response to a particular drug. Once scientists discovered that people's genes show small variations (or changes) in their nucleotide (DNA base) content, all of that changed—genetic testing for predicting drug response is now possible. Pharmacogenomics is a science that examines the inherited variations in genes that dictate drug response and explores the ways these variations can be used to predict whether a patient will have a good response to a drug, a bad response to a drug, or no response at all.

So what challenges must pharmoacgenomics overcome before we can reap its purported benefits? The latest issue of PLOS Medicine has an informative paper on that topic (here) by Jesse J. Swen et. al., entitled "Translating Pharmacogenomics: Challenges on the Road to the Clinic". Here is a sample:

Because variation in drug responses is, at least to some extent, related to genetic variation, PGx testing has the potential to result in safer and more effective use of drugs by permitting individualized therapy. In recent years FDA-approved PGx tests have become available, but the use of PGx testing has remained limited, largely by a lack of scientific evidence for improved patient care by PGx testing. Providing this scientific evidence presents a significant challenge. The development of novel tests should be aimed at solving important clinical problems. To demonstrate potential for clinical use, PGx studies should report diagnostic test criteria. For PGx tests shown to improve patient care, guidelines directing the clinical use of PGx test results should be developed. Information on cost-effectiveness and cost-consequences of PGx testing should be provided to facilitate reimbursement by insurance companies. Finally, uptake in clinical practice will be given a stimulus if regulatory agencies recommend testing prior to prescribing the drug, and if pharmaceutical companies or patient groups advocate for use of the test. If the outlined challenges can be met, the incorporation of PGx in routine clinical practice may prove an achievable goal in the near future.