Pharmacogenomics & Personalized Medicine: New Ways to Optimize Drug Therapy


Pharmacogenomics--or PGx--shows great promise for predicting drug responses in individual patients for treatment of a variety of disease states.

Pharmacogenomics--or PGx--shows great promise for predicting drug responses in individual patients for treatment of a variety of disease states.

The term pharmacogenomics comes from the combination of 2 words: pharmacology and genomics.

  • Pharmacology is the study of how drugs work in the body and genomics is the study of characteristics that result from an organism's complete set of DNA.
  • Pharmacogenomics is the study of genetic factors that influence how a drug works

Personalized medicine refers to the use of genetic or other molecular biomarker information to improve the safety, effectiveness, and health outcomes of patients by risk stratification, prevention, and tailored management approaches.


It is well known that drug therapy doesn’t work for all patients all of the time. Clinical research has provided insights into various factors that impact how drugs work for different patients, including disease state, comorbidities, concomitant drugs, nutritional state, and pharmacogenomics (PGx). PGx is the study of how gene variations and the different ways genes are expressed can impact how an individual responds to drugs. Genes can influence how drugs work in the body because they determine the structure and composition of human proteins, including enzymes, receptors, transporters, and other molecules, which are involved in disease progression and drug pathways.

Information provided through PGx can be predictive, pharmacokinetic (affecting drug concentrations in the blood or tissues), and/or pharmacodynamic (affecting drug action in the body). Significant developments in the field of genetics are enabling health care providers, pharmacists, patients, and payers to think about new ways to optimize drug therapy.

Personalized Medicine

Personalized medicine is based on a foundation of scientific and medical knowledge that evaluates both inherited and acquired treatment risks to optimize management and outcomes for patients. Improvements in health outcomes such as mortality, morbidity, or disability are the primary end points in assessing the utility of genetic testing in personalized medicine. Although health care providers and payers currently rely on evidencebased information about available drugs to help provide guidance on appropriate use, an understanding of the genetic variables that influence how a drug responds could also help pharmaceutical companies design more effective new therapies.

The importance of genomics in the selection of a drug therapy and ongoing patient management is accepted today—and it is expected to expand in the coming years. A growing number of genomic tests have significant public health impact, including predictive tests to help physicians choose the right drug and dosage for individual patients. PGx is currently being used to predict drug responses in the treatment of cardiac, psychiatric, autoimmune, and infectious diseases, cancer, and more.

Genetic test results can be used to determine if a patient is more or less likely to develop a disease or condition, inform the selection and appropriate dosage of a drug therapy, predict the progression of a disease or the efficacy of a therapy, and monitor treatment. PGx testing allows for the rapid identification and exclusion of patients at risk of experiencing adverse drug effects as well as those who are predicted not to respond to a specific treatment. This information can be used to individualize and optimize the treatment by selecting the most appropriate drug and/or dose.

As an example, variations in drug response can result from common differences found in enzymes that metabolize certain drugs. One family of enzymes, known as the cytochrome P450 (CYP)-containing enzymes, are responsible for inactivating numerous classes of drugs as well as activating prodrugs such as clopidogrel. If patients have a less active or inactive form of CYP enzymes, they are unable to inactivate and efficiently eliminate a drug from the body—“poor metabolizers”— which can cause the drug to build up and lead to severe adverse events or overdose. On the other hand, patients with very active forms of CYP enzymes—“ultrarapid metabolizers”— can cause the body to eliminate a drug before it has had a chance to work.

Pharmacogenomic Tests

Importance of Test Interpretation, Actionability, and Education

Numerous genomic tests are making their way from the laboratory bench into the clinic. There is a critical need for expertise in evaluating the clinical utility of these tests and providing a proper interpretation of test results. Professional guidelines with specific and actionable clinical recommendations on how to individualize medication, according to a PGx test result, are essential if current knowledge is to be used to improve drug therapy. Although information about PGx is currently found on some FDA drug labels (for example, Plavix, Coumadin, Erbitux, and Herceptin), definitive information about how to act on test results is often lacking.

The information is typically classified into 3 categories—test required, test recommended, and “information only”—which are expected to guide the clinical use of PGx tests for reaching a therapeutic decision. (See Table of “FDA Valid Genomic Biomarkers in the Context of Approved Drug Labels” at ResearchAreas/Pharmacogenetics/ ucm083378.htm.)

The translation of PGx into clinical practice will require the education of physicians, pharmacists, and other health care professionals in the application of genetics to therapeutic interventions and patient management. Incentives through reimbursement, performance feedback, and peer group comparisons may be used to encourage physicians and patients to adopt PGx as part of their routine testing strategy for specific therapy decisions.

What is Genetic Benefit Management?

Genetic Benefit Management refers to a systematic, comprehensive, and cost-effective process for optimizing the use of genetic information and genetic testing to help control plan costs and improve members’ health. In some cases, a Genetic Benefit Management program helps manage the cost associated with testing, whereas in others resulting clinical interventions may help ensure genetic information is used to inform or influence treatment protocols such as prescription drug therapy.

The Generation Health-CVS Caremark partnership provides clients with expertise in clinical criteria and evidence- based methodology to support the identification of genetic testing opportunities and the translation of these opportunities into Genetic Benefit Management programs. Access to Generation Health’s certified Best Test Genetics Network, a preferred provider organization of laboratories selected for their advanced scientific methods, assures high quality and accurate testing with reliable turnaround times and good value. Experienced genetic counselors and clinicians are available to educate and inform physicians and members about PGx testing opportunities and assist with the interpretation of test results.

PGx and Specialty Pharmacy

PGx programs in specialty pharmacy support the safe and appropriate use of these effective, yet often expensive and sometimes high-risk medications to promote better clinical outcomes for patients. In specialty pharmacy, criteria for utilization management programs have been developed using FDA-approved and compendia-listed indications for specialty and oncology therapies (Table). For example, medical oncologists and hematologists are able to individualize and tailor cancer treatment by identifying genetic variations that contribute to drug efficacy and/or the risk of toxicity. The classic example of a targeted therapy, Herceptin, is highly effective in the 15% to 25% of breast cancers that have a particular genetic variant that causes an overexpression of the HER2 protein (a cell growth promoter), and is not effective against breast tumors lacking HER2 overexpression.

Cancer therapy and anti-infective drug therapy provide the best examples of situations in which significant progress is achieved by PGx testing of the drug target as well as the genomes of the individual, the tumor or the infectious agent (eg, virus). In the treatment of hepatitis C virus, identifying the viral genotype is important in determining the dose of the drugs and duration of therapy, and can also identify resistance to new targeted drugs, such as protease inhibitors.

PGx Impact and the Payer Perspective

It is essential to evaluate the clinical utility of PGx testing, including the risks, costs, and benefits relative to use of the available alternatives. These data are particularly useful to third party payers who may be covering the cost of PGx testing. For example, given the high incidence of cancerand treatment-associated toxicities and the costs of treating cancer and protecting patients from toxicities, it is useful to demonstrate a pharmacoeconomic benefit using PGx testing for targeted therapies. Cost-effectiveness researchers are examining parameters like the cost of a PGx test, morbidity due to adverse drug reactions, prevalence of the genotype being tested, and whether test results would change providers’ clinical decisions in ways that improve patient outcomes.

Coverage of PGx tests that are not required by a FDA label varies, depending mostly on the plan’s determination of whether the test is “medically necessary.” Coverage decisions are further complicated by the fact that many PGx tests are novel, have not been rigorously studied, and have not been subjected to a comprehensive comparative effectiveness analysis. In fact, the data needed for an ideal analysis may not be available until years after a test is marketed.

Formulary placement is key to any health plan’s ability to negotiate drug prices, guide drug use, and control spending. Formularies are typically built on the concept of “therapeutic equivalence” within drug classes, including promoting the use of generics and allowing the selection of a preferred drug with exclusion or financial penalties for nonpreferred alternatives. PGx can facilitate this tier structure by uncovering clinically important therapeutic differences or similarities within drug classes and identifying new subcategories of disease based on genetic information.


The goal of PGx is to develop and implement evidence-based approaches to predict drug response in individual patients and, ultimately, personalize therapy. The results of diagnostic and predictive PGx tests may ultimately inform formulary placement, step therapy, and other clinical treatment algorithms. Genetic information could also be leveraged for any future treatment with drugs metabolized by the same pathway or those having the same mechanism of action. Because PGx enables physicians to prescribe more accurately and results in faster, more effective therapy with fewer side effects, it can deliver significant savings throughout the health care system. SPT

Dr. Martell is Director of Clinical Content Strategy and Ms. Senich is Senior Vice President and Chief Marketing Officer at Generation Health, Inc. Generation Health is a health management company that specializes in assisting employers and other health care payers to manage medical costs and improve their employees’ and members’ health by assuring optimal utilization of genetic testing.

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