Pharmacogenetics and the boy who cried revolution

Everyone is trying to disrupt the inert, resource-gobbling juggernaut collectively referred to as “healthcare.” It feels like we constantly hear about a new start-up, university incubator-backed group of students, or even peer-reviewed journal article proposing ground-breaking solutions that tackle the various failures or inefficiencies plaguing healthcare. And it appears to me that the preferred term being excessively bandied about is “revolution.” So much so that the word is beginning to lose meaning. We’re at a tipping point.I, for one, welcome the great toppling of this tattered, exhausting word. Because the sexy allure of a “health care revolution” is just a mirage masking a vast desert of status quo. I probably don’t need to spell out why to such an informed audience, but I have a word limit to hit. So here goes nothing. Note that this isn’t an exhaustive list.Healthcare must contend with time-starved professionals that have little bandwidth to learn drastically new approaches or systems, even if they’re backed by high quality evidence. Finance departments often don’t have additional funds to pay for implementation. Electronic systems lack inter-operability to integrate with all the digital revolutions available.My take? The only way to meaningfully revolutionize health care is to chop up the revolution in question into homeopathic-sized doses and administer them one at a time. Is it even a revolution anymore? In other words, incremental change is the only realistic path forward, in this author’s opinion.And you know what’s a great example of an already incremental innovation often wrapped in a revolution’s clothing? Sorry, dumb question. You already read the title of the article.For those in the back row, it’s pharmacogenetics (PGx).Most pharmacists know a thing or three about pharmacogenetics. But there’s a subcutaneous layer to PGx that is frequently ignored. Let’s pierce the skin.An oftenunder-appreciated aspect of PGx is that it only serves as an additional input into decision-making. Though in some cases its importance may supersede other factors, it usurps nothing within a holistic approach to medication selection. Broad evidence-based treatment guidelines, specific patient factors and professional judgement must always have a seat at the table.It is simply one additional investigation to consider when deciding whether to initiate, adjust or stop a medication, and often serves to corroborate a past medication experience. The caveat being that it only serves said purposes when sufficiently strong data exists for the drug-gene variant combination(s) in question. In other words, it’s an incremental set of data points that bring us closer to achieving the aspirational standard enshrined by our beloved pharmaco-adage ‘give the right drug, at the right dose, to the right patient, at the right time.’And this is exactly in our wheelhouse, as pharmacists. Certainly, underlying principles of genetics are foundational, but clinical implementation relies on a level of intimacy with concepts like pharmacokinetics, pharmacodynamics, first pass effect and dose response that few other professions, if any, possess as a core competency.If this sounds similar to something else we do better than anyone else, then it should. (For the folks now asleep in the back row, I am referring to drug interaction management.) So any time you’re initiating a prescription, doing a therapeutic check of another provider’s prescription, adapting a pre-existing therapy, or providing any other aspect of pharmaceutical care, and you’re considering everything you would normally consider, think about the next increment.For example, say your patient had a stroke recently and appears to have been appropriately prescribed clopidogrel based on clinical factors. By checking their PGx results during a routine interaction, you can verify if they have variants reducing their ability to convert clopidogrel it to its active form, thereby impeding its effectiveness. Practically speaking, this translates to opening their PGx report, looking up clopidogrel and reading the short blurb next to it to see what the implications are, before taking the necessary actions within a broader, holistic framework (just like you would for any other routine reason for concern). Remember what I said about chopping up the revolution into micro-doses? Heck, there’s even a quick and dirty validated scoring tool called ABCD-GENE that combines clinical and genetic factors when using clopidogrel.I can acknowledge that this is an ideal scenario. At no point did I mention the effort involved to educate the patient about testing, encouraging them to get tested, and the logistics involved. I know that some of you early adopters already do this, with not an insignificant amount of effort involved. But here’s the thing—some of your patients have already been tested, or are taking it upon themselves to do so, or are at least already considering it. And you may not be aware of this, because if they have been tested, they may only be bringing their results to their physician or nurse practitioner.So, if we want incremental progress, the first thing you need to do is simply ask them if they’ve already been tested and act accordingly if they have. If they haven’t, this can nudge them into looking into it themselves and perhaps even serve as informal market research for your pharmacy. The rest will follow later—following my silly homeopathy analogy, it’s important to stay nicely diluted for now.Viva la revolución. Sort of.Notes to the reader: Don’t worry, I don’t actually believe in homeopathy.I would love to know what you think of a series of short, digestible articles exploring oft-under looked aspects of PGx that you might not typically come across – off-the-mark humour optional. Comment below, please!

Pharmacogenetics and the boy who cried revolution

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