A deeper look at pharmacogenomics: How it’s impacting patients and providers

Why does the same drug have differing responses – or none at all – in different patients?

This is a question that clinicians and researchers have grappled with over the course of modern medicine. Now, the study of pharmacogenomics is starting to provide answers to this question, which could drastically impact how patients’ medication therapy is provided for years to come.

Pharmacogenomics is the study of genes that are involved in the responses to a drug. What we know now is that certain genes determine unobservable characteristics—like how we metabolize drugs and nutrients. Variables, such as patient’s smoking status or the co-administration of certain other medications, have also been shown to influence drug metabolism and therapeutic effects.

Over the past several decades, important work has been done to identify the specific enzyme systems involved in drug metabolism for many drugs. Pharmacogenomics has brought us an understanding of interpatient variability in drug response—down to the level of the gene in predicting a patient’s metabolizer status.

There are known drug-metabolic enzyme systems that are influenced by particular expressions of a gene. These systems can be categorized by how the body metabolizes specific drugs. The categories of a patient’s predicted metabolizer status (or metabolism phenotype) are: ultrarapid metabolizer, rapid metabolizer, normal-extensive metabolizer, intermediate metabolizer, and poor metabolizer.

In most cases, ultrarapid metabolizers may require a higher dose of an active drug to achieve the appropriate therapeutic response. Whereas a poor metabolizer of a drug may require a lower dose, or an alternate drug, because the drug is metabolized and eliminated slowly from the body so that the impact of the drug is more pronounced.

Individual patient factors such as age, sex, comorbidities, other drug therapies, and lifestyle (e.g. smoking) must be also be considered alongside a patient’s phentotype, making a strong case for the development of robust clinical decision tools to coincide with the practice of pharmacogenomics.

While pharmacogenomics has made great strides, the need for clinical decision support tools to produce accurate and actionable information is vitally important for the effectiveness of the technology to expand.

Fortunately, there is work being done for clinical decision support by companies. Several universities and companies are also providing pharmacogenomics certification programs such as RxGenomix and Manchester University. In addition, the American Pharmacists Association supports a curriculum for pharmacogenomics education.

Clinicians also decide who should have pharmacogenetic testing. This has important implications, as there are cancer therapies that won’t be administered without a genetic test, due to the risk of non-response in the patient. Additionally, we’ve also found many metabolizing enzyme variants for drugs that treat chronic conditions like hypertension, diabetes and high cholesterol. There are also more specific tests for medications for pain management, depression, clotting disorders, seizures and other conditions.

Much of the interest in the public sector around this topic can be attributed to the popularity of genetic ancestry tests like 23andMe, AncestryDNA and MyHeritage DNA, which may open the pathway to more people opting for pharmacogenetic testing. Recently, 23andMe even received approval to apply the pharmacogenomic panel in their tests, but the Food & Drug Administration (FDA) warned that consumers should not use the test to make treatment decisions based on their own results and instead consult with a licensed healthcare provider.

As we further the pharmacogenomic practice, information security and the need to protect genetic information is paramount. In 2008, the Genetic Information Nondiscrimination Act was signed into law to protect individuals from discrimination based on genetics, or genetic predisposition, to a disease. The Act doesn’t apply to life or disability insurance.

Meanwhile, work to standardize data transmission and security protocols continues and, like many other software tools, integration of the pharmacogenetics data into the primary source of patient information should continue—ideally in a way that a patient can control access. 

Pharmacogenomics could also provide an area of opportunity for pharmacists, who are well-suited to expand their clinical practice skills into this area as provider status legislation is making its way through the states and point of care testing becomes more common. Retail independent pharmacists are increasingly performing point of care testing and typically have the time needed for evaluation and patient education, interpretation, and communication of recommendations of therapy changes to other members of the patient’s healthcare team.

Another promising area is in the resources and tools helping to advance pharmacogenomics. For example, PharmGKB is a pharmacogenomics knowledge base focused on the impact of human genetic variation on drug responses through various means, including pharmacogenomics information for drugs into their FDA drug labeling. Another important resource for pharmacogenomics information is the Clinical Pharmacogenetics Implementation Consortium (CPIC), and the Pharmacogenomics Research Network. CPIC is an international consortium focused on facilitating the use of pharmacogenetic testing for patient care by removing the barriers to testing. 

However, acceptance of pharmacogenomics as an integral part of drug therapy by payers will be needed to increase the rate of testing across patient segments. The integration of pharmacogenomic data into the primary source of patient information will also be necessary for care providers and pharmacists to help improve patient response to drug therapies.

Although the practice of pharmacogenomics is still emerging, it is evident that medication therapy is just one more facet of patient care that is becoming much more personalized.