Variability in drug response can be explained, in part, by genetic differences among patients. A clear role in drug toxicity and efficacy has been established for some gene-drug combinations, yet implementation of pharmacogenomic tests in clinical practice lags behind this knowledge. The evidence–adoption gap for many pharmacogenomic tests can be addressed in the short term through the development of consensus-based practice guidelines and clinician education.
For genetic variants associated with severe drug toxicities, there is a strong impetus for adoption. An example is the HLA-B*15:02 variant, associated with the potentially lethal Stevens-Johnson syndrome in Asian patients treated with carbamazepine.1 Another example is the poor metabolizers of cytochrome p450 2D6 substrates that represent a range of risk when exposed to specific medications. The death of a child treated with fluoxetine illustrates the importance of identifying patients with impaired metabolism as well as the ethical dilemma of knowingly exposing patients with minimal metabolic capacity to substrates that require a specific enzyme for clearance.2
The adoption of testing for genetic variants that have a more modest effect on drug response or risk of adverse events has been more variable. In oncology, somatic mutation or expression tests for specific drug targets in tumors (eg, EGFR, ERBB2) can provide a clear indication for treatment efficacy, and rates of adoption have been relatively high. However, the current evidence for other pharmacogenomic tests for efficacy determination is less clear. For example, patients of European ancestry who carry the higher-activity allele of a serotonin transporter gene variant have a modest increased probability of responding to serotonin reuptake inhibitors.3 The decision to use testing to increase the probability of a good response must be weighed against other issues, such as the efficacy and cost of alternative treatment options. Because the cost of testing is decreasing, cost is less likely to pose a barrier.