Technology in laboratory medicine has been growing in leaps and bounds, and not just because of the demand for better and faster COVID-19 testing. Advances in pharmacogenomics (PGx), which looks at a patient’s genetic background to determine whether a specific drug or a specific drug dose will be effective, is bringing a new level of precision medicine to patient care.
We asked Sherin Shaaban, MD, PhD, FACMG, to explain how the progress in instruments, methods, and other areas has influenced uptake of PGx testing. Shaaban is the medical director of pharmacogenetics and molecular genetics and genomics at ARUP Laboratories in Salt Lake City, Utah. She is also an assistant professor of pathology at the University of Utah School of Medicine.
How do you see advancements in lab technology like real-time PCR, microarrays, and mass spec contributing to the adoption of PGx?
These technologies contribute in multiple ways, including that they enable high throughput testing of clinically actionable variants. In other words, a laboratory can test many variants for many genes and offer that testing to many patients.
The field is moving rapidly too. Technologies can reveal genome-wide information. That helps laboratory test for more variants, but it also enables discovery. We end up identifying variants that we didn’t even realize play a role in PGx.
We can make a case that these technologies are still relatively inexpensive when we consider the benefits that come from them. Many of these platforms have come down significantly in cost, so investing in them doesn’t impose a heavy financial load on an institute that is thinking of adopting PGx.
Think about prescribing the same dose of medicine for each person. It’s not going to work for everybody. Giving people the wrong dose, or drugs that won’t work, costs the U.S. economy billions of dollars in terms of doctor visits, hospitalizations, and side effects. Considering those costs, the investment in the platforms and providing PGx tests are cost-effective.
How can the infrastructure built up for molecular testing from COVID-19 testing contribute to the expansion or adoption of PGx?
So many labs invested in instrumentation and creating labs specifically for COVID-19 testing. They can really capitalize on that trained workforce, especially as some of those same technologies could be used for PGx testing.
In addition, some companies and vendors allow for exchange of instrumentation. So that COVID-19 testing infrastructure wasn’t totally wasted effort or investment, and it potentially can be translated into an investment into PGx.
Where do you see opportunities for better collaboration in lab medicine in PGx?
I think there is huge room for collaboration because few labs perform PGx right now, and PGx is one of those specialties that really requires experience. A lab with PGx expertise can help another lab build up their program and share their experiences and challenges they faced in adopting the technology so that a laboratory new to PGx can avoid the same problems.
As the field increasingly moves toward precision medicine, PGx will be a major player in the field. Collaborations between those who have experience in conducting those PGx tests, and those who don’t but are interested and don’t know where to start, are going to be critical moving forward.
Laboratorians also have opportunities to work with pharmacists who can bridge the gap between laboratory testing and physicians. They can help translate the results into actionable insights for physicians about the choice and dosage of specific medications.
What do you see as the most exciting areas where PGx is becoming standard of care?
PGx really allows us to tailor treatments for better patient care. We’re moving to the era of precision medicine where each one of us should be treated individually. One size does not fit all, and PGx is enabling clinicians to know not just that a given drug will work, but also that the patient will need a specific dose to avoid developing side effects.
Alternatively, we can say that a drug won’t work on a particular patient so we’re not wasting the patient’s time or our time—or more importantly, avoid a drug that could harm the patient.
There are several major areas where PGx has become critical: oncology, psychiatry, gastroenterology, and cardiology to name a few. Many physicians in these specialties are quite savvy about PGx testing and implementation, especially at major academic medical centers. The goal is to have more physicians in other specialties and in various health care settings more comfortable ordering and interpreting PGx testing. Clinical studies and scientific evidence are building up in many other specialties where PGx can play a role in patient care.
Are there areas where clinical evidence is limiting PGx?
Just like we need more studies, we need larger studies. In the U.S., we need a larger number of institutes to enroll more patients to give us the strong evidence we need. In February 2023, a European study published in the Lancet, with data collected across 18 hospitals, examined a 12-gene PGx panel. The study showed the clinical utility of pre-emptive PGx testing reducing adverse drug reactions by a third, which in turn is predicted to translate into a significant economic value for PGx implementation. The same authors are working on a cost-effectiveness analysis to be published separately.
We need to be conducting these kinds of larger studies at more institutions in the U.S., such as what the National Institutes of Health is doing with the All of Us research program, which includes PGx. That’s especially needed because diversity still is a major limitation when it comes to PGx research. Most studies right now are conducted among Caucasians. So, we need not just larger studies, but also more inclusive studies.
What are the barriers to greater use of PGx?
With the expansion of next generation sequencing in molecular testing, laboratories will be dealing with a large number of variants. Translating these findings into data the providers can understand and use in patient management is not an easy task.
Variants of unknown significance in particular, where we do not know if the effect of such variant is benign or pathogenic, are problematic. Providers could find that data confusing or not helpful, which could deter them from ordering PGx testing. That is why we need to invest in more functional studies to help identify the role of these kinds of variants. There’s still more work to do.
The debate about the clinical utility of PGx is still ongoing. Some believe the evidence about PGx’s effectiveness is still not there—and of course advocates for PGx counter that. Others will say it’s cost prohibitive, and that instead of being able to just prescribe a drug, PGx is adding an additional layer of testing (and cost) and hence it becomes a limitation.
Moreover, provider education is a must. Without proper efforts to educate physicians in various specialties about which PGx tests to order and how to interpret the results, providers’ discomfort ordering such tests will continue to be a bottleneck in practice.
How can clinical laboratorians better educate clinicians?
Laboratories should be able to offer consultations. I receive calls all the time from providers who, for one reason or another, ordered a PGx test, but they really don’t know what to do with the results. These consultations are very valuable both to the lab and to the clinician.
Consultations also can encourage those who are interested in PGx but are a little hesitant about it. And it can help others who doubt their ability to interpret results so that they gain more confidence. Additionally, we also should be part of those research studies we were talking about earlier. We’re a critical player in that work.
Another effective way to broaden education and acceptance around PGx is through scientific meetings. There, we also can listen to providers and see why they think PGx has limited clinical utility. If you can rebut those ideas and communicate the value of PGx—that would be a valuable outcome. Lastly, advocacy efforts with decision makers, whether within one’s institute or at the national level, could be another way to encourage PGx adoption.
Jen A. Miller is a freelance journalist who lives in Audubon, New Jersey. +Twitter: @byJenAMiller