In this era of personalized medicine, the field of pharmacogenomics is experiencing significant growth and growing interest. Pharmacogenomic (or pharmacogenetic) testing analyzes specific genetic variants to better understand how a person may respond to medications (1).
Because medication use is pervasive for treating a variety of conditions, pharmacogenomics offers a type of genetic information that could impact many of us. Current medical practice often relies on a trial-and-error approach to prescribing medications. The initial choice and dose of medications may be based on population data, but individuals vary significantly in the way they respond. Only about 50%–75% of individuals taking a medication will have the intended response (2). The goals of pharmacogenomic testing are to shorten the trial-and-error period, optimize medication dosage, and reduce the risk of side effects.
It’s important to note that pharmacogenomic information is still relatively new and somewhat limited. Genetics are not the only factor that influences a person’s response to medications. Other factors include sex, age, race, other medications, other medical conditions, and diet. In addition, not all medications have enough—or any—data to support changing prescribing guidelines based on genetic test results. Clinical guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and PharmGKB, can help clinicians sort out the utility of pharmacogenomic testing for their patients (3, 4, 5, 6).
Service Delivery and Stakeholders
The delivery of pharmacogenomic testing involves numerous factors, such as assessment of the utility or appropriateness of testing, test choice, interpretation of complex results, and informed consent. Patients increasingly seek a high level of personalized care—including pharmacogenomics—so it is important to model best practices for testing and service delivery, which should include multiple stakeholders. In addition to the patients themselves, these stakeholders include laboratories, insurance companies, providers, pharmacists, and genetic counselors.
When weighing lab and test options, keep in mind that each lab has its own unique list of medication-genes covered by their test. If clinicians are interested in a specific medication, they need to make sure the lab and test includes it. Some labs offer smaller, disease-specific panels, while others offer broader panels covering many diseases, genes, and medicines. Although reference labs commonly offer gene panels, third-party payers may not cover them, which can leave the patient or billing institution with uncovered charges. The recent trends in coverage policies have been positive, but it’s important to consider each patient’s coverage as well as affordable self-pay options.
There are many healthcare providers who should be involved in developing institutional practices for pharmacogenomic testing. For example, genetic counselors and pharmacists can serve as excellent resources. Genetic counselors have expertise in genetic test selection, paired with unique training in communicating complex genetic information and risk. They are trained to empower patients with information so that patients can make an informed decision.
Additionally, genetic counselors are an important patient resource when it comes to incidental findings, such as implications around the inclusion of the APOE gene on many pharmacogenomic panels, and implications for family members, such as the dominant inheritance of malignant hyperthermia genes.
Pharmacists have specialized training in pharmacodynamics and application of pharmacogenomic data, such as for medication adjustment. Pharmacists also are able to assess past medication history and appropriateness of such testing for a given patient. In both instances, pharmacogenomic testing is a natural extension of the services these professionals provide, and their complementary training makes them an excellent choice when considering collaborative working relationships for service delivery.
Ideally, a clinical pharmacogenomic program would integrate several disciplines, including medical genetics, genetic counseling, health informatics, pharmacy, pharmacology, clinical pathology, and laboratories. However, it may not be realistic for all institutions, particularly those in rural or community centers, to have access to these specialty providers. At a minimum, the genetic counselor and pharmacist partnership can be quite effective, especially when working with specialties such as oncology, cardiology, pain management, psychology, neurology, and infectious disease, which all have established drug and gene pairs and could benefit from pharmacogenomic services.
In our own practice, we started with evaluating frequency of medication use and associated toxicity in our clinic, researching CPIC guidelines, and assessing test availability and costs. We then developed a multidisciplinary process in which the patient is identified as a candidate for testing via the electronic medical record system, counseling is provided by the pharmacist and genetic counselor, testing is ordered by the provider, and results with recommendations are communicated to the patient and ordering provider by the genetic counselor and pharmacist. This allows for the patient to receive necessary pretest counseling that covers benefits and, more importantly, limitations with pharmacogenomic testing. This kind of informed consent process sets the patient up with reasonable expectations and an evidence-based plan of care.
Pharmacogenomics in Action: A Case Example
A 19-year-old female presented to a primary care clinic for evaluation with pharmacogenomic testing. The patient had an uncontrolled pain experience during a recent spinal surgery and was nervous about undergoing a second surgery for hardware removal. The patient met with a multidisciplinary team that included a pharmacist, genetic counselor, and physician.
The pharmacist reviewed the patient’s medication history and initially determined she may benefit from CYP2D6-guided pain control. The pharmacist and genetic counselor were able to address the utility of pharmacogenomic testing in the context of pain and the limitations of this testing. The genetic counselor also was able to provide supportive counseling around the patient’s anxiety, manage expectations, and provide informed consent.
After the pretest counseling session, the patient chose to move forward with testing and was found to be a CYP2D6*2/*4 intermediate metabolizer, which is associated with reduced formation of active metabolites for opioids metabolized by CYP2D6. In the case of intermediate metabolizers, CPIC guidelines recommend initiating standard therapy and monitoring for adequate analgesic response before selecting an alternative agent. However, the patient was worried about having insufficient pain relief from medications such as codeine, and her primary care physician was able to recommend alternatives to CYP2D6 substrates for her upcoming surgery.
This case example demonstrates the clinical utility of pharmacogenomic testing and highlights the benefits of a collaborative multidisciplinary pharmacogenomic service delivery model.
- Weinshilboum RM, Wang L. Pharmacogenomics: Precision medicine and drug response. Mayo Clin Proc 2017;92:1711.
- Spear BB, Heath-Chiozzi M, Huff J. Clinical application of pharmacogenetics. Trends Mol Med 2001; :201–4.
- Relling MV, Klein TE. CPIC: Clinical pharmacogenetics implementation consortium of the pharmacogenomics research network. Clin. Pharmacol Ther 2011;89:464–7.
- Whirl-Carrillo M, McDonagh EM, Hebert JM, et al. Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther 2012;92:414-7.
- Swen JJ, Wilting I, de Goede AL, et al. Pharmacogenetics: From bench to byte. Clin Pharmacol Ther 2008;83:781-7.
- Swen JJ, Nijenhuis M, de Boer A, et al. Pharmacogenetics: From bench to byte--an update of guidelines. Clin Pharmacol Ther 2011;89:662–73.
Jennifer Eichmeyer, MS, CGC, is a clinical assistant professor at Boise State University in Boise, Idaho. +Email: [email protected]
Christine Munro, MS, MPH, CGC, is a genetic counselor at UPMC Children’s Hospital of Pittsburgh. +Email: [email protected]