Written by Julie Bick, Ph.D.
Pharmacogenomics (PGx) is the study of how genes affect a person’s response to drugs, and it represents a relatively easy and low-cost entry point into personalized medicine. The goal of PGx is to tailor medical treatments to individuals based on their genetic makeup, improving drug efficacy and minimizing the risks of adverse effects. Despite its growing role in healthcare, some skepticism lingers. In this blog, we'll explore why some people remain unconvinced of its value to patients, and ultimately how barriers to the adoption of PGx will be overcome within the healthcare sector.
One of the most significant advantages of PGx is its ability to personalize drug therapies, making them safer and more effective. Different individuals respond to medications in various ways due to genetic differences. PGx helps identify which patients are likely to benefit from a specific drug and who may experience adverse effects that in extreme cases can be lethal. For example, variations in the CYP450 enzyme genes can affect how a person metabolizes common drugs like antidepressants, anticoagulants, or pain medications. Knowing this can prevent ineffective treatments or dangerous side effects. In fact, adverse drug reactions (ADRs) are a major concern in medicine and are responsible for a large number of hospitalizations and, in some cases, fatalities. PGx testing can significantly reduce the occurrence of ADRs by identifying patients who might be at risk based on their genetic profiles. This allows for adjustments in dosages or the selection of alternative medications, creating safer treatment plans (Ritchie, 2012)
While PGx testing may seem expensive initially, by preventing trial-and-error prescriptions, reducing ADRs, and enhancing drug efficacy, PGx has been shown to lower healthcare costs on many levels- fewer hospital admissions, emergency room visits, and complications arising from improper medications ultimately save both healthcare systems and patients money. Furthermore, when patients experience fewer side effects and see better outcomes, they are more likely to adhere to their prescribed treatments. PGx can also empower patients by providing a clear rationale for their prescribed medications, increasing their understanding and engagement with their healthcare (Giri et. al. 2019).
Despite its clear benefits, not everyone is convinced that PGx should be a standard part of healthcare. Several factors contribute to this skepticism, but essentially cynics point out that there are many factors that influence a patient’s response to a medication such as age, sex, underlying conditions and other medications; and although this is true, the fact is that only rarely do prescribing physicians consider even these factors when selecting medication doses. What is needed is a shift in the paradigm of medication management, and for the standard-of-care to include a personalized/precision medicine approach.
Unfortunately, healthcare is a field where established practices and protocols are deeply ingrained, with some clinicians hesitant to change their approach based on new technologies or genetic insights that have not yet become the standard of care. There is no doubt that the slow pace of integrating PGx into clinical guidelines and decision-making tools has contributed to its delayed adoption. This has not been helped by the lack of consistent PGx protocols- while there are some very clear PGx guidelines, such as those from the Clinical Pharmacogenetics Implementation Consortium (CPIC), the application of these guidelines can be inconsistent across healthcare systems. It is also true that PGx is a maturing field of medicine, and as such there are many gaps in our knowledge of certain gene variants, especially rare variants and their impact in drug metabolism (see reference for more details: National Academies of Sciences, Engineering, and Medicine; Division of Behavioral and Social Sciences and Education; Health and Medicine Division; Committee on Population; Board on Health Sciences Policy; Committee on the Use of Race, Ethnicity, and Ancestry as Population Descriptors in Genomics Research. Using Population Descriptors in Genetics and Genomics Research: A New Framework for an Evolving Field. Washington (DC): National Academies Press (US); 2023 Mar 14. PMID: 36989389). This creates uncertainty for both physicians and patients about when and how to use PGx results, and the lack of clear protocols can fuel doubts about the utility and reliability of PGx, leading many to adopt a wait and see policy before integrating PGx testing into their practice.
Another factor is the cost, and even though PGx can be extremely cost-effective in the long run, the upfront costs for genetic testing can be prohibitive for some patients and healthcare providers. In regions where healthcare budgets are tight, or where insurance does not cover genetic testing, the adoption PGx into routine practice that then might direct the physician to more expensive drugs, can seem financially impractical. In addition, anytime genetic information is involved, questions about privacy and ethics arise. Some individuals fear that PGx testing might lead to genetic discrimination, especially if this information is shared with insurance companies or employers. While there are laws in place in many countries to protect against this, the fear of misuse of genetic data remains a barrier to widespread acceptance.
While there is a growing body of research supporting PGx, some critics argue that the clinical utility of PGx has not been proven for all drugs and conditions. For certain medications, there is still limited evidence showing a clear benefit from tailoring treatments based on genetic information, and for many conditions, traditional approaches to drug prescription still yield positive results without needing genetic testing. However, the truth is PGx has been shown in many studies to benefit patients, and the major hurdle to widespread PGx adoption is a lack of awareness of these benefits (Giri et. al. 2019). Many healthcare professionals and patients are simply unaware of the field of PGx, and many physicians may not have received formal training in genetics or personalized medicine. Without this foundational knowledge, it’s difficult for healthcare providers to spend time to incorporate PGx into their practice or confidently recommend genetic testing to patients. This has led to a gap between the science around PGx and its practical application, which ultimately is limiting the broader adoption of PGx.
But probably one of the most difficult hurdles to the adoption of PGx is that it isn’t perfect. Even though nothing in medicine is perfect, many PGx sceptics have used this to dismiss the utility of PGx. As we mentioned earlier in this blog, there are in fact several factors outside of a patient’s genetics that can influence how they respond to a drug (Luscombe DK, 1977). These include physiological, environmental, and lifestyle-related elements, as well as patient-specific factors, all coupled with the patient’s genetic profile (Miao et. al. 2007). The age of the patient is perhaps the most obvious one. Metabolism changes with age, and older adults often have slower metabolism and reduced kidney and liver function, which can lead to slower drug clearance. This increases the risk of drug accumulation as well as the rates and severity of side effects. On the other hand, children metabolize certain drugs differently than adults, often requiring adjusted dosages, and PGx in these instances can only provide guidance for dosing, along with risk of ADRs.
Another obvious factor is a patient’s body weight and composition (particularly their % body fat) since these affect the volume of distribution of a drug, particularly for fat-soluble medications. A patient with higher body fat may need different dosing than someone with more lean body mass for drugs like clopidogrel (Wagner et. al. 2014) Heavier individuals may require higher doses, while lower doses may be needed for those with lower body weight to achieve the desired therapeutic effect. The sex of the patient is also a consideration since for example women have different levels of enzymes and may experience different side effects or require different dosages for certain drugs than men; in fact, studies show that woman are more frequently overdosed than men (Soldin and Mattison, 2009).
Underlying chronic conditions such as diabetes, heart disease, or autoimmune disorders can also affect how drugs are metabolized or absorbed. For example, gastrointestinal conditions (e.g., Crohn's disease) can affect the absorption of oral medications through the gut, whereas severe infections often reduce liver function, thereby altering drug metabolism. Research is increasingly showing that the gut microbiome plays a significant role in drug metabolism, with individual variations in microbiota influencing drug response (Pant et. al. 2023).
Patients taking multiple medications may experience drug-drug interactions, or one drug can inhibit or induce enzymes that metabolize other medications they are taking, leading to altered drug levels and effects. Similarly, certain foods and herbal supplements can interfere with drug metabolism; grapefruit juice is probably the most identified of these since it can inhibit the CYP3A4 enzyme, increasing the blood concentration of certain medications and leading to potential toxicity. Some drugs need to be taken with food to enhance absorption, while others may be less effective when taken with certain foods, so it is important that the patient understands and follows the drug labels.
There are many reasons why clinicians encourage their patients to quit smoking- but in regard to medication management, smoking induces certain liver enzymes (like CYP1A2), which can increase the metabolism of drugs such as caffeine, theophylline, and some antipsychotics. Tobacco smoke can also induce epigenetic changes, such as hypermethylation of detoxification genes like GSTP1, which encodes glutathione S-transferase, a key enzyme in the detoxification of many drugs, and potentially altering drug metabolism and detoxification pathways. As a result, smokers often require enhanced monitoring to ensure optimal drug dosing, efficacy and safety.
So yes, there are certainly many factors that contribute to a patient’s response to a medication, some of which are more challenging to assess than others; but a patient’s PGx profile is a central contributor to mediation response, and one that does not alter over a lifetime. As big data and omics become more integrated into clinical decision making, shouldn’t PGx be front and center of this?
Although PGx offers a personalized approach to medication, it is only one piece of the puzzle when it comes to predicting drug responses. However, the bottom line is that the integration of PGx testing into the standard of care has the potential to transform modern healthcare by offering a more personalized, efficient, and safer approach to drug therapy. One of the most compelling arguments for the widespread adoption of PGx testing is its ability to significantly reduce adverse drug reactions (ADRs), which are a leading cause of hospitalizations and death. Once in a lifetime, pre-emptive PGx testing, would identify patients at risk of severe reactions to specific drugs and avoid harmful medications. This proactive approach would enhance patient safety, reduce the need for emergency interventions, and ultimately save lives. PGx testing has already demonstrated its effectiveness in preventing life-threatening reactions to drugs like warfarin, clopidogrel, and abacavir, where specific genetic variants are known to increase risk. By tailoring drug therapies based on an individual’s genetic profile, PGx testing is helping to ensure that patients receive medications that are both safe and effective for them.
Today, most healthcare professional acknowledge that the current “one-size-fits-all” model of prescribing drugs often leads to suboptimal results, and PGx testing provides a simple and valuable tool for healthcare providers to tailor treatments and maximizing drug efficacy. For conditions like cancer, depression, and cardiovascular diseases, where treatment response can vary widely, PGx testing ensures that patients are given the right drug at the right dose, reducing the need for trial-and-error prescribing. This personalized approach not only improves therapeutic outcomes but also enhances patient satisfaction, as patients experience better symptom control and faster recovery with fewer side effects. In fields like oncology, PGx-guided treatments have already shown superior outcomes in targeting cancer therapies to individual genetic markers, making the argument for PGx integration in other medical disciplines more compelling (Truesdell et. al. 2024).
From the payer perspective, studies have shown that PGx-guided treatment can reduce overall healthcare spending, particularly in chronic disease management and polypharmacy scenarios, where inappropriate medications can lead to costly complications (Verbelen et. al. 2017, Apted and Huff, 2023). For example, patients with multiple prescriptions benefit from PGx testing by avoiding harmful drug interactions and receiving the most effective medications tailored to their metabolic profiles.
Regulatory bodies like the FDA and European Medicines Agency (EMA) already recommend or require PGx testing for certain high-risk drugs, recognizing its importance in ensuring safe and effective treatment. As the body of evidence supporting PGx testing grows, expanding its use to a broader range of medications will align with regulatory best practices. Moreover, from an ethical standpoint, healthcare providers have a responsibility to offer the best possible care to their patients. By not integrating PGx testing into standard practice, clinicians risk exposing patients to unnecessary harm through suboptimal drug choices. PGx testing empowers both doctors and patients with critical information that can prevent harm, optimize treatment, and uphold the ethical principle of “do no harm.”
As our understanding of genetics and its impact on drug response deepens, PGx testing will become an essential tool in advancing precision medicine. The integration of PGx testing with electronic health records (EHR) and decision-support tools will make the process seamless, allowing healthcare providers to access genetic information easily and use it in real-time clinical decision-making, to ultimately support streamlining care, enhancing treatment outcomes, and ensuring that patients receive the most informed and effective therapies.
The integration of PGx testing into the standard of care is no longer a question of possibility but of necessity. The benefits of PGx testing are clear: it enhances patient safety, increases the effectiveness of treatments, reduces healthcare costs, and advances the future of personalized medicine. As the evidence for its utility continues to grow, PGx testing represents the next logical step in delivering safe, efficient, and personalized care. Within the context of the opposing drivers of cost and drug efficacy, healthcare must be as precise and patient centered as possible, adopting PGx testing as a standard of care is not just an option, it’s a responsibility.
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