The practice of pharmacology has been around for thousands of years, starting with Pythagoras’ observations of how fava beans directly impacted the prevalence of hemolytic anemia, a blood disorder that causes weakness and fatigue, in individuals that consumed them.1 In the millennia following, researchers continued to explore what caused certain reactions with early treatments. In the 1950s, the idea of testing for how individuals react to different drugs started to formalize into a substantial clinical application.2 The emergence of genomic technologies including genotyping decades later helped formalize the process and the term pharmacogenomics was coined to help define the burgeoning area of study.3
Pharmacogenomics (PGx) is used to understand how variations in key areas of an individual's DNA may impact efficacy of a medication, dosage considerations, as well as exploring potential adverse drug reactions (ADRs). Ideally, this is performed in advance of prescribing medication so that the physician or the pharmacist can streamline medication selection, reduce trial-and-error, and minimize ADRs. Alternatively, it is done to help explain why a medication is not working or causing an ADR and get the individual back on the best therapeutic path. A wide-reaching PGx study showed that 100 percent of individuals assessed had at least one gene that was known to impact medication outcomes, while 66 percent of the same population had genetic risks detected for medicines that they were already prescribed to take.4 The data exemplified how almost everybody receiving treatment have the potential to be impacted by not receiving PGx assessments and could benefit from such testing/assessments.
What is holding back PGx as standard of care
PGx is not a widely adopted practice despite the benefits it could provide, for two core reasons: an unclear path to reimbursement including demonstrated longer term economic value and its lack of broad utilization among clinicians (and subsequently, patients). Although there are extensive findings demonstrating the clinical utility of PGx testing to impact better health outcomes, reimbursement of these tests is only recently becoming available through real-world implementation studies demonstrating economic value to payers.
In addition to economic drivers, utilization of PGx testing to assist with medication prescribing and its benefit is still in its infancy. Despite being easy to implement within molecular testing laboratories, there are very few clinicians who truly understand how to utilize PGx for medication management. Since clinicians who can order tests often do not know how to interpret the results, the demand of testing is still relatively low. With stakeholders across the healthcare delivery chain unaware of the value or the new means of economic viability, widespread adoption across a meaningful scope has been challenging.
Bringing PGx forward
Illustrating how PGx can help provide better health outcomes while saving time and costs for the healthcare system and payers is key in bringing it to the mainstream. Researchers and test manufacturers have an obligation to continue presenting the data that show how PGx can help advance care across different disease areas. In addition, technology providers would need to educate laboratory technicians and clinicians how to interpret the results that are found with such testing. Areas where PGx research is showing promise, as well as returns already, include oncology, cardiology, pain management, peri- and post-operative care, mental health, geriatric care, and many more.
Oncology: Oncologists can utilize PGx to help assess patients to determine which chemotherapies will be most effective, and the medication dosage patients can tolerate. These care improvements are critical in a disease state where speed, efficiency, and accuracy are key.5 These benefits are clear when applied at the point-of-care or during the prescription stage, but they have also been shown to potentially provide benefits later in the care journey for people living with cancer, in terms of treating residual effects of the disease or in limiting potential negative after effects.6
Analyzing even two genes can help to make a big difference in how individuals are treated, and how much those treatments help them, as has already been shown in the clinic.7 Recent studies of people with non-Hodgkin's lymphoma taking rituximab demonstrated that people with the FcγRIIIA genotype, determined by a single nucleotide polymorphism (SNP) at residue 158, had a considerable increased reaction than those without that genotype. Other cancer researchers have shown an understanding of how different genes, such as TPMT, UGT1A1 an DPYD, work with the toxicity of different drugs and treatment-limiting tolerabilities and have already shown those benefits at the bedside.8
Pain: Hundreds of millions of people struggle with various degrees of pain, and are forced to manage it with medication, costing almost six hundred billion dollars every year.9 PGx can help find pain management therapies that work with a specific genetic makeup to avoid drugs that will be damaging to them in the long run and can potentially identify individuals that are susceptible to opioid-addiction.10 Already, particular CYP2D6 gene variants have been identified that impact codeine and tramadol prescriptions and their ability to have a positive or negative impact on patients.11 The OPRM1 and COMT genes are just among the many others that are currently being assessed to find out how they impact future opioid dosages.
Mental health: For individuals struggling with a variety of mental illnesses, such as depression, having to go through a trial-and-error approach through ineffective drugs can be a massive struggle. Some people can take months, if not years, to find an antidepressant to work for them, building up costs and causing additional issues by having persistent depression.12 Each medication that they try can take four to six weeks alone to fully understand whether or not it will have a clinical benefit or if it will even be tolerable. PGx would provide the opportunity to find a treatment that would be most effective in the first instance, cutting out not only wasted time, but wasted money as well; this doesn’t even begin to explore how much of a toll different side effects can have during those trial periods.13 In a recent study, pharmacogenomic testing was shown to potentially save almost $4,000 annually for people living with depression.14
Advancements already made
Therapeutic areas, such as neurological diseases, cardiovascular disease, respiratory illnesses, autoimmune disorders, and more can find similar benefits if PGx is applied on a broader scale, which is already beginning to be proven. A team of researchers, led by Dr. Phil Empey from University of Pittsburgh School of Pharmacy, launched the Pharmacogenomics-guided Care to Improve the Safety and Effectiveness of Medications (PreCISE-Rx) program in 2015, which created a streamlined process for testing individuals as soon as they arrived at the University of Pittsburgh Medical Center (UPMC) and added any gene–drug reaction findings to their electronic health records.15 The program has already tested thousands of patients and has made this sort of testing routine in their approach to care.
Overall health is improved when people find the treatments that can address their medical issue through PGx. Clinicians can save time by reducing the need to revisit with patients to discuss new treatment alternatives, and the clinician/patient relationship is improved by building trust through more successful initial treatments. Money can be saved for patients and the industry at large with therapeutics not being given to individuals who will not tolerate or will not react positively to them. The applications of PGx are far reaching and more can be learned in the future.
Research already conducted has shown that over 85 percent of neurological PGx case studies, including depression and schizophrenia, assessed showed cost savings, specifically in studies that assessed CYP2D6 and CYP2C19 drug-gene interactions, showing how the long-held promise has already started to reap benefits.16
Many independent organizations and working groups have formed to help bring PGx into the standard of care as well. The STRIPE Collaborative Community was formed in 2020 to bring together members of the PGx community, as well as the FDA, to address challenges the industry is facing to make precision medicine mainstream. The Pharmacogene Variation (PharmVar) Consortium and PharmGKB are different public databases that seek to share information on drug and gene variants to help those working in the field. The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes peer-reviewed guidelines to facilitate the translation of PGx data into actionable prescription algorithms. All of these groups working together in recent years has advanced the space and helped to democratize data for those that could benefit from it.
Test manufacturers have already been working to make the bold promise of making PGx more of a reality. Considerable leaps have been made especially following the advancement of and investments in diagnostics during the COVID-19 pandemic. Infrastructure that was widely distributed and implemented during the peak of the pandemic helped improve diagnostic technology accessibility by labs around the United States; those same platforms and personnel can now be used to run PGx tests. The evolution of leveraging relationships developed during the pandemic and offering new molecular tests can help replace testing revenues as COVID-19 testing volumes, as well as the test demand for other infectious diseases, decline.
Additionally, technology has advanced in the ability to identify and assess genes on a larger scale, accelerating research. Elements like artificial intelligence have brought this even further along, allowing for automated assessments of genes. That improvement in machine learning, paired with the advancements made in diagnostic tools that help to pair personalized treatments with the right individuals has put PGx in a better place than ever to have real, concrete applications in the medical world.
Increased awareness of the benefits of PGx testing could lead to a general uptick in demand. Laboratorians and technology providers are in a great position to help clinicians to understand when and how to order PGx testing, and downstream interpretation of results. It has been shown that clinicians don’t have the time alone to teach themselves how to implement PGx, so utilizing the investment made in diagnostics over the past few pandemic-riddled years from both industry and governments, can help to get everyone up to the same level.17 All of these groups working together in tandem to call for the benefits that PGx provides could help drive demand, and in turn, help accelerate its adoption across the industry.
Pharmacogenomics has moved quickly in recent years to become a viable piece of the overall healthcare puzzle, serving to identify effective treatments by figuring out which therapy could work best with each individual based on their individual genomic makeup. The field has been growing and can be a key element in bringing personalized care on to a broader scale.
PGx can lead to better overall quality of care by making sure that medications are prescribed with the specific individual in mind rather than guessing what may work best under the “standard of care” paradigm. It can help reduce costs and time wasted among hospitals, pharmacies, and healthcare providers by cutting down on outpatient visits used for trial-and-error approaches to find a medication that will be effective and on emergency room visits and hospital stays due to adverse drug reactions.18 Patients are helped through reduced amount of time for medical visits, struggling with specific diseases, and possible side effects of drugs they struggle to tolerate. Overall, PGx has the potential to greatly reduce costs for the healthcare system, patients, insurers, and patients’ employers.
Test manufacturers have continued to improve their diagnostics, helping make them easier to implement at a lower cost per sample than they were before. This is profitable to testing laboratories and can help provide economic value to the payers as well. In turn, those working within the different stages of the health delivery system have an obligation to learn more about tools that are readily available now in order to help them provide a better overall experience, reduce disparities in care, and save time. Personalized care has long held substantial promise, and now, that promise can be fulfilled. The next big step is for the industry and the medical community to come together to help see this through.
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