By Prachiti Dalvi

Structure of Codeine

Codeine is an opioid pain medication; but if you are a poor metabolizer of a particular enzyme (CYP2D6), you will experience no pain relief from this drug. However, if your doctor could administer something called pharmacogenetic testing, she would know to simply give you morphine (an active metabolite of codeine) instead. For now, this kind of testing isn’t available.

Mary Relling, PharmD

Mary V. Relling, PharmD, the Chair of Pharmaceutical Sciences at St. Jude’s Children Hospital spoke about the need to implement pharmacogenetic testing on Thursday, January 10. A number of  tests have recently emerged that are ready for prime time. When we know that some drugs may have adverse effects for people with  particular genetic phenotypes, it is unethical to prescribe these drugs without knowing the patient’s genetic status.

However, Relling said there are a number of barriers to integrating pharmacogenetic tests into clinical care: fragmentation of our healthcare system, a focus on sick-care rather than disease prevention, a lack of evidence for clinical utility or cost-effectiveness, complex underlying lab results, and a lack of a centralized system for recording patient information.

The best way to break through these barriers is to conduct testing preemptively, Relling said. We can simply take drop of blood when the baby is born and run genetic tests. “Genetic tests are lifetime results. It makes sense to have it in the background, just as we know a patient’s age, weight, sex, etc.,” Relling said. The barriers discussed above can be avoided to a certain extent at St. Jude’s because they have adopted a team approach to patient care and a 100% electronic system for recording patient records.

The growing affordability of genotyping makes using preemptive pharmacogenetic testing more feasible, she said. The cost of sequencing one or two genes in the past will now produce results for 225 genes. Two years ago, the Clinical Pharmacogenetics Implementation Consortium (CPIC) studied how to migrate pharmacogenetic testing from the laboratory into routine patient care. They looked for gene-drug pairs associated with potential risks of life-threatening toxicity, serious adverse effects, or lack of effectiveness. Eleven of the genes CPIC determined met the threshold for high-risk were found to have profound effects on 33 drugs.

Relling said approximately 48% of patients receiving drugs at St. Jude’s received orders for at least one of those pharmacogenetically high-risk medications.

She said the question now is how to use genetic test results rather than whether a genetic test should be ordered. In the coming years, we will have to address how to maintain the fine balance of providing the clinician with enough information to treat the patient and overwhelming the patient with genetic testing results that are difficult to interpret.

This lecture was a part of the Genomics and Personalized Medicine Forum sponsored by the Duke Institute for Genome Sciences and Policy (IGSP).