Personalized Medicine is in the Genes
Published on 15 January 2020
Established in the 1950s, the field of pharmacogenetics, the study of how one particular gene can impact a pharmacologic response from a drug, has grown to be one of the most promising areas in revolutionizing personalized medicine. With the establishment of consortiums like the Clinical Pharmacogenetics Implementation Consortium and pharmacogenomics knowledge resources like PharmGKB, pharmacogenetics data has become more accessible to clinicians, creating opportunities to provide more personalized and efficient patient care.
As more gene-drug data is compiled and commercial genotyping panels become more affordable, pharmacogenetics has become more applicable in clinical practice, especially within the fields of oncology, cardiology and psychiatry. Some payers are even including genotyping panels within patient coverage when certain criteria are met.
Pharmacogenetics has made great strides in the last decade, but there are still obstacles that keep it from becoming a routine part of patient care. From integration into the electronic health record to clinician education, pharmacogenetics needs champions from all disciplines in health care to fully realize its potential.
Getting into Practice
"There has been a definite uptick in the use of pharmacogenetics in clinical practice," said Christina Aquilante, Pharm.D., FCCP, professor at University of Colorado Skaggs School of Pharmacy and Pharmaceutical Science, and member of the University of Colorado Center for Personalized Medicine, where she is working on a system to integrate a patient's genetic information into the UCHealth electronic health record. "Two of the most common areas where we are seeing pharmacogenetics applied are in using the CYP2C19 genetic makeup to inform antiplatelet therapy drug selection in patients who have had stents placed in their coronary arteries and in the area of psychiatry, for example, to inform depression therapy."
More than 35 medications have clinical practice guidelines for how to use genetic information pertaining to those medications. Data like this create the opportunity to bypass or lessen the trial-and-error process of finding the right drug therapy for a patient.
"When patients take a medication, the effectiveness and the risk of side effects are directly linked to how their body processes medications," said Gloria Grice, Pharm.D., FNAP, BCPS, professor of pharmacy practice, assistant dean for curriculum and assessment and interim chair of the Department of Pharmacy Practice at St. Louis College of Pharmacy. "Everything that is happening inside of the body when a medication is taken – the absorption, distribution, metabolism and excretion of the medication – all of that can be influenced by how a patient's genes function. If a patient takes a medication and it’s not working, there may be a genetic reason for that."
In January 2013, the Food and Drug Administration released "Guidance for Industry, Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical Studies and Recommendations for Labeling," a guide intended to assist new drug developers and investigators in evaluating how variations in the human genome could affect a patient’s pharmacological response to a drug.
The guide provides recommendations on when and how genomic information should be considered in anticipation of questions that arise during drug development and regulatory review. Though the guide only provides suggestions, the encouragement of drug development teams and investigators to generate genomic hypotheses to influence later trials is a clear indication of both the importance of compiling this data for future reference and the potential for routine implementation of pharmacogenetics in patient care.
Integration and Education
However, the necessary infrastructure to support routine clinical application is in the very early stages of development. There are two approaches that can be taken when implementing pharmacogenetics into patient care – preemptive and reactive. More often than not, clinicians will resort to the reactive approach, requesting a test for a specific gene at the time of or after a medication is prescribed.
"The ideal scenario is to use the preemptive approach of having everyone genotyped before a medication is needed," Aquilante said. "It’s challenging because preemptive testing is not always covered by insurance. Also, you need to integrate that information into the electronic health record in a discreet and structured way with built-in clinical decision support tools that can surface that genetic information, accompanied by recommendations to providers at the point of care when a relevant medication is prescribed."
Another, more immediate, obstacle that has impeded the wider application of pharmacogenetics in patient care is the lack of pharmacogenetics knowledge among practicing clinicians. Skepticism remains about whether or not implementation of pharmacogenetics improves patient outcomes, and though there is far more accessible gene-drug data, the implementation of pharmacogenetics testing is not ubiquitous across health care, suggesting to some that this may just be a passing fad.
"Certainly, there are some cases where pharmacogenetics testing has little impact on improving patient outcomes, but there also are examples of gene pairs where the evidence is very strong and does merit implementation," Aquilante explained. "Not all genetic information merits implementation into clinical practice. Just as we practice evidence-based medicine for everything else we do in pharmacy and medicine, we want to do the same in pharmacogenetics. Pharmacogenetics is another tool in the clinical pharmacology toolkit. It's another piece of information that providers can use and factor into their clinical decision-making process."
Clinician education is a key component of growing the application of pharmacogenetics testing in clinical settings because many clinicians did not receive formal training or education on pharmacogenetics when they were students. This lack of education has left some practitioners apprehensive about the burgeoning field.
To meet this need, several universities and colleges across the United States have begun to provide continuing education (CE) courses and certificate programs for clinicians from all disciplines to form a basic understanding of pharmacogenetics testing, nomenclature, how to evaluate the evidence and how to discern what information merits clinical application – because without their active participation in learning and sharing this knowledge with their colleagues and students, the field can only grow so much.
Poised to Lead the Charge
"Pharmacogenetics is very much an interdisciplinary field," said Brian Gage, M.D., professor of medicine at Washington University School of Medicine in St. Louis and principal investigator on Genetics Informatics Trial of Warfarin Therapy to Prevent DVT. "If you look at the leaders in pharmacogenetics, they come from all different backgrounds. Pharmacists play a key role in this research, including translating the results of pharmacogenetics studies into clinical practice. Physicians get comparatively little training on drug-drug interactions and even less instruction about pharmacogenetics."
A pharmacist's specialized knowledge and expertise has positioned them as the ideal candidate to usher pharmacogenetics into routine practice, and accrediting agencies such as the Accreditation Council for Pharmacy Education (ACPE) are taking notice. ACPE has included in its standards the integration of pharmacogenetics into the pharmacy curriculum, though it is up to the institution how it is integrated.
"I think it's important to educate our students on what has been done and is known, but we also need to be proactive and educate them on what is up and coming and might become more prevalent once they graduate and go into practice," said Michelle Jeon, Pharm.D., BCACP, who currently serves as assistant professor of pharmacy practice at the College and completed a certificate program in pharmacogenomics. "That requires a different mindset from faculty because we have to stay ahead of the curve and prepare our students for future practice."
As the standard issued by ACPE has not been rigidly defined, pharmacy institutions across the country are integrating pharmacogenetics into the curriculum in a variety of ways. From standalone courses to a more continuous threading of pharmacogenetics throughout the curricula, pharmacy schools are working to find the right approach.
St. Louis College of Pharmacy is taking a thorough look at how to integrate pharmacogenetics into the curriculum and has encouraged faculty to take advantage of CE opportunities in the growing field.
"We are doing a complete analysis of where it is being taught in our curriculum and to what degree and depth," Grice said. "One of my goals for this year is to identify if we are doing enough in this area, and it is a top priority item for me that we expose students to it regularly and often. It's about the anticipation of wider clinical application."
The Future of Personalized Medicine
The potential for pharmacogenetics to revolutionize personalized medicine is undeniable, but it is not to be mistaken for a magic bullet. What makes the field of pharmacogenetics so appealing and exciting is the possibility that comes with having a new piece of information that brings the picture of a patient into sharper focus.
"Pharmacogenetics is a great opportunity to gain a different perspective on how our bodies affect the medications we take," Jeon said. "Historically, we've been very good about understanding the makeup of the molecules of the medications themselves, but we haven't really been able to tie that to how those molecules are affected by a person's genes. With pharmacogenetics, we are able to collect a bit more information to make a more informed decision and provide truly personalized care."
This story was first published in the fall 2019 issue of Script magazine. To read past issues of the magazine, visit the Script magazine archive.