Clinical application of pharmacogenomics: The good, the bad and the aesthetically unappealing

Pharmacogenomic tests are an extremely useful tool for prescribing medication – so why isn’t every doctor on the bandwagon?

Many physicians are underusing a valuable toy in their clinical tool-box.   Stavos/Flickr  (CC BY-NC-ND 2.0)  

Many physicians are underusing a valuable toy in their clinical tool-box. Stavos/Flickr (CC BY-NC-ND 2.0) 


Gene Dosage is a monthly column by Janan Arslan that finds out what genome science is uncovering about each individual's unique response to drugs and pharmaceuticals. Janan is a graduate student and pharmacogenomics researcher with a keen interest in personalised medicine.

November is all about transformation here at Lateral, and pharmacogenomics really has transformed the way we think about drugs. I can't think of a better time to introduce you not only to the clinical application of pharmacogenomics, both at home and across the world, but also to the many barriers that prevent its complete clinical adoption. I’ve often been speaking of pharmacogenomics as though it’s still theoretical, but it’s not – there are many companies and institutions heavily involved in its implementation, but naturally not everyone is aware of them. Lack of awareness is just one of several issues.

A pharmacogenomics test can predict how patients will respond to drug therapy based on their genes. A 2012 survey of US physicians revealed a “basic tenet that pharmacogenomics has clinical relevance”. Yet many physicians, although open to incorporating pharmacogenomics testing in their practices, were not adequately informed of the test's availability and applicability. Lack of adoption also seems to be linked with a physician’s training: doctors who were trained in genomic markers were more likely to adopt pharmacogenomics testing than those who weren’t. 

Over the course of my career and my interactions with various medical professionals, I’ve found this to ring true. It isn't that no one wants to use the test; it’s usually a lack of awareness or knowledge about its use. These factors were a driving force behind the founding in 2007 of GenesFX Health, the first pharmacogenomics testing institution in Australia, and also my first employer within the field.

Some treating physicians are uncertain on how to use pharmacogenomics in their clinics .  Calvinnivlac/Flickr  (CC BY-NC-ND 2.0)

Some treating physicians are uncertain on how to use pharmacogenomics in their clinics. Calvinnivlac/Flickr (CC BY-NC-ND 2.0)

The conversion of raw genetic data into useful clinical information can be difficult. Companies like GenesFX exist to provide user-friendly pharmacogenomics reporting to treating physicians to assist with current and future prescribing practices.

Over the course of my columns, I’ve religiously mentioned the CYP genes, those involved in the metabolism of antidepressants and painkillers. The CYP genes that are tested at GenesFX include CYP2D6, CYP2C19 and CYP2C9, with CYP3A4 soon to be added to “the menu.” Most physicians opt to order a comprehensive report that incorporates the above CYPs with an additional gene, VKORC1. The latter gene is involved in the metabolism of warfarin, an anticoagulant (we’ll delve into the mechanics of that later). Alternatively, you can also order individual drug-gene tests.

The test has slowly gained popularity in clinical practices across Australia. I recently attended a week-long intensive course at the Royal Children’s Hospital, and was pleasantly surprised to see so many speakers demonstrating the clinical relevance of pharmacogenomics in their fields. Over the past few years, GenesFX Health have collaborated with the Victorian government to develop a pharmacogenomics test request system for Melbourne-based hospitals.

I eventually left GenesFX to pursue my career in the US. Before I left, I was under the impression that, technology-wise, there were advances in the US that were absent in Australia. In reality, the tests offered in both nations are almost mirrored, albeit with some discrepancies in terms of reporting formats. 

Hmm. I see how this can get complicated…   Bea & Txema/Flickr  (CC BY-NC 2.0)

Hmm. I see how this can get complicated… Bea & Txema/Flickr (CC BY-NC 2.0)

A prospective study by the Institute for Prospective Technological Studies back in 2006 reviewed the social and economic impact of pharmacogenetics and pharmacogenomics testing in Europe and the US. According to the study, the US has established itself as an industry leader due to the sheer number of small to medium-sized pharmacogenomics enterprises in development since the 1990s (while Europe has only been in the game since 1998). There are indeed many US companies specialising in personalised medicine, so it’s really the quantity of providers — compared to our lone ranger here in Australia — that gives the impression that US pharmacogenomics progression is advanced. While the US does hold the upper hand in industry leadership, Europe holds the crown for more public research groups since 2005. 

Irrespective of my place of employment, the challenges in the test’s clinical implementation remained uncannily similar. Besides the lack of training in understanding and using pharmacogenomics, and in handling genetic data, other implementation issues – such as the cost-effectiveness of pharmacogenomics testing and reimbursement – have delayed its clinical use. 

In Australia, genetic tests are not yet covered by Medicare, except for one gene, TPMT (again, to be left for later). Patients wanting a pharmacogenomics test must pay out of their own pocket; a quick look at GenesFX’s site suggests a cost of $145 for a multi-gene test. Reimbursement is also an issue in the US, but there it is considerably more complex — you are required to collaborate with Medicare, Medicaid, and insurance companies. While Medicare is accessible to all Australians, US Medicare and Medicaid are social insurance organisations that assist elderly, disabled, or low-income individuals and families.

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    Physicians have a lot to learn from pharmacogenomics.     GotCredit/Flickr  (CC BY 2.0)

Physicians have a lot to learn from pharmacogenomics. GotCredit/Flickr (CC BY 2.0)

Back in 2008, Deloitte Economics Australia conducted a comprehensive pharmacoeconomics analysis, in which they reviewed the cost-effectiveness of pharmacogenomics for different areas of medicine and drug classes. For the anticoagulant warfarin, they projected a saving of A$5.7 billion over the course of ten years. For the chemotherapeutic tamoxifen, they estimated a saving of A$6.5 million over the course of five years. These projections incorporate precise prescribing, which includes avoiding the costs associated with adverse drug events, such as hospitalisation. 

Policy makers are trying to create regulations suited to pharmacogenomics testing. This year, the US Food and Drug Administration (FDA) called out to the personalised medicine community to help shape future regulatory measures. They’ve received responses from such organisations as the Personalized Medicine Coalition, who have provided commentary on several topics, including optimal access to high-quality diagnostic tests, the incorporation of new scientific discoveries, and curating data for clinical use.

Whichever way you look at it, the aim of pharmacogenomics testing is to alter current diagnosis methods, deviating from the trial-and-error method of prescribing medication. Overall, we are trying to change treating physicians’ diagnostic thinking by providing a clinical-decision support tool. From my perspective, education and training is the key to this change. Yes, people like me do go out and speak to treating physicians and try to be of service. But we do need more than a few overly enthusiastic pharmacogenomicists.

There are courses in the US designed to teach health professionals about using pharmacogenomics, such as the University of California’s (San Diego) PharmGenEd course. Even in Australia, some universities are incorporating pharmacogenomics into their coursework, such as Charles Sturt University’s Molecular Pathology subject, and the University of Newcastle’s Pharmacogenomics and Personalised Health Care subject.

The clinical implementation of any test, really, is never an easy task. But I believe it is well worthwhile. Personally, I’ve had the pleasure of not only speaking to treating physicians but to many beautiful patients as well, who have all expressed a great appreciation for the test. From their collective perspectives, the test is empowering and provides an explanation for why some patients respond to their treatment in the manner that they do. The patients’ experience in particular is always embedded in my mind. It is with this motivation that I continually advocate the use of pharmacogenomics testing, and work diligently with physicians to make this a reality for all patients.