Pharmacogenetics in Practice: Pharmacists’ Role in Navigating Clinical Challenges and Consensus Building in the Field

Pharmacy Times interviewed Ryan Nelson, PharmD, medical director of precision medicine at ARUP Laboratories, on his participation in the Standardizing Laboratory Practices in Pharmacogenomics (STRIPE) Annual Meeting and Consensus Workshop at US Pharmacopeia (USP) headquarters in Rockville, Maryland, where he led discussions on pharmacogenetic challenges in clinical practice. Nelson explained that a primary focus of the meeting was the need for aligned guidelines across major organizations, including FDA, European Medicines Agency (EMA), Clinical Pharmacogenetics Implementation Consortium (CPIC), and National Comprehensive Cancer Network (NCCN), particularly around DPYD genotype-guided chemotherapy dosing for certain cancer treatments. Nelson highlighted the role of the new MetaCensus platform in this work, as it’s a collaborative tool designed to facilitate open access to evidence sharing, review, and consensus voting, promoting a transparent and distributed approach to evidence evaluation.

Ryan Nelson, PharmD, presents at the STRIPE Annual Meeting and Consensus Workshop at US Pharmacopeia headquarters in Rockville, Maryland, on evaluating evidence review processes for pharmacogenetic testing.

Nelson also discussed the essential role pharmacists play in pharmacogenomics, both as clinical consultants and as researchers, and underscored the importance of multidisciplinary collaboration across specialties to enhance pharmacotherapy. While pharmacy has traditionally been well-represented in the field of pharmacogenomics, he stressed that integration with other health care professions is vital to advancing clinical outcomes. The ultimate goal of STRIPE’s initiatives, Nelson explained, is to make pharmacogenomics seamlessly integrated into routine clinical practice, allowing pharmacists, physicians, and other clinicians to share the responsibility of delivering precision medicine without overburdening any one group.

Nelson also called on all health care professionals to participate in STRIPE’s collaborative mission, advocating for a collective commitment to addressing current challenges and driving better, more universally applicable pharmacogenetic standards.

Pharmacy Times: What is the workshop you participated in at the STRIPE Annual Meeting and Consensus Workshop, and what is the objective of the group?

Ryan Nelson, PharmD: The workshop I participated in was clinical challenges. One of the bigger challenges with pharmacogenetics is there's sometimes conflicting recommendations and guidelines or a lack of a recommendation in a guideline, [so] trying to figure out what to do can be quite difficult. So, we had a few statements that were specifically targeting inter-organizational collaboration.

Ryan Nelson, PharmD, moderates a panel discussion on evaluating evidence review processes for PGx testing, with a focus on DPYD genotype-guided chemotherapy.

So, for instance, yesterday, the session that I moderated was around DPYD genotype-guided chemotherapy. Currently, FDA, EMA, Dutch Pharmacogenetics Working Group (DPWG), and CPIC all have recommendations to lead people with dosing based on DPYD genotype for floral pyrimidines. One very important group, perhaps the most important group to medical oncologists, is NCCN, which does not currently recommend DPYD genotype-guided floral pyrimidines. So, we have made some statements of consensus around trying to get people from CPIC or from the pharmacogenetics community that have a lot of experience in this realm, representing the evidence that vindicates clinical implementation from their perspective, to be put for consideration in NCCN guideline deliberations. We want to similarly have people from NCCN and American Heart Association also going back to CPIC to participate in their guidelines. As we get more heterogeneous representation through these groups, I think we could have a better understanding of each perspective a little better and hopefully come out with a more robust and well-represented conclusion.

We also made some consensus statements around a project that I presented on today, which is called MetaCensus, which is a distributed ledger that allows for evidence submission, evidence analysis and review, and then evidence voting, as well as meta-analysis. The platform was meant to be an open access tool that allows anyone to participate on the platform that can be credentialed and that can keep an indelible ledger of your actions. So as you develop this topic with DPYD genotype-guided floral pyrimidines, a collaborative group has begun to grow and form that can now leverage this platform, regardless of what entity or agency or college you work for, and be able to represent different viewpoints, those being insurers, clinicians, regulatory entities, guideline-producing entities, so that we can really start to have a better understanding of how our biases impact our blind spots in how we assess clinical evidence, and how that might differ from different specialties, doing the same as we start to look at those in aggregate in doing multicriteria decision analysis, we're capable of producing a more contextualized and clearer picture of where the current lapse in data are that need to be further investigated with our next round of experimentation that hopefully will be able to expedite the process with National Institutes of Health and their grant funding mechanism, so that we have, over time, better representation of very distilled gaps in the data that we think are most important to prioritize. The process tomorrow with voting on these consensus statements is going to be done on the MetaCensus platform as well. One of the platform features is being able to make proposition statements that others can vote on within the platform, and that will be one of the main focuses tomorrow.

Pharmacy Times: What should pharmacy professionals understand about the intended outcomes of the STRIPE Annual Meeting and Consensus Workshop for the field of pharmacogenomics?

Nelson: I think the most important thing to come from this meeting, from my perspective, is we are working very hard to really provide solutions to problems that have been long standing in pharmacogenetics. We have some incredibly bright, highly impactful scientists and clinicians that have had answers for a very long time on these important topics that can improve pharmacotherapy that have not been fully implicated in the actual impact they can have widespread. The discussion yesterday about DPYD—we still have a lot of opportunity with a very old drug to improve how we are using the drug. STRIPE really does have a central mission around bringing everybody together, finding ways forward, and doing so in a democratized fashion.

Pharmacy Times: Within your work in pharmacogenomics, how many pharmacists do you work with and what is the role of pharmacists in that work?

Nelson: So, I'm probably the odd duck here. At ARUP [Laboratories], I'm the only pharmacist. In my role as the medical director of precision medicine—most other medical directors are MDs, PhDs, or MD/PhDs. The pharmacists that I do work with are at other institutions, especially ones with STRIPE, so that work usually looks like clinical consults where someone has a problem case that I will help consult on or with research projects like MetaCensus, or some of the other stuff that we're doing with STRIPE; it's a lot of the more collaborative research pieces.

The pharmacist field, I do think, is very central to pharmacogenetics. It's kind of something that we have stewarded for the majority of its existence. We are trying to change that to some extent though. We want to be one piece of the equation. We need physicians, genetic counselors, nurses, nurse practitioners, and physician assistants all relevant to this process. We don't want to have a turf war over something that everybody should know.

Pharmacy Times: Within the shared collaborative environment of your work in pharmacogenomics, how are pharmacists viewed within that work?

Nelson: I don't see a turf war. I do see that the field has very well represented themselves with PharmDs, because it's closest to what we already specialized in. So, pharmacokinetics, pharmacodynamics, and pharmacogenetics are kind of a continuum of each other. I think that pharmacists just kind of innately have that driver, because it's so close to everything that we do at the core of medicines, is trying to understand how to use them more appropriately. We don't have a strong diagnostic component during pharmacy school—we focus on drugs, and I think that that's very central to what we're doing here, and that this is just one of many tools that pharmacists need to know. I think that one of the bigger challenges with pharmacogenetics is that sometimes, I think people who are really excited about it tend to only see pharmacogenetics, and they think that it's going to solve all the problems in pharmacotherapy, but it's one of many tools that a sound clinician would want to leverage to be the best clinician they can.

Pharmacy Times: What is your hope for the future of pharmacogenomics, and how do you view Standardizing Laboratory Practices in Pharmacogenomics (STRIPE) within that future?

Nelson: I would like to see pharmacogenetics—germline pharmacogenetics, at least, on the clinical topics that we're talking about now, become very boring and happening in the background and easily implemented and happening in its right place in the clinic, which is usually one of the bigger problems and lamentations of any clinician is they have too much work to do in too little time. We are asking for them to add yet another thing to the table here, and I think as we become cleverer and more elegant about the solutions that we're trying to implement, that some of these features can be happening in the background.

One specific example that I think shines well here is at Moffitt Cancer Center with J. Kevin Hicks, PharmD, PhD, FCCP, who worked with the infectious disease team to implement CYP2C19 genotype-guided voriconazole (Vfend; Pfizer). The way that it was implemented there was very clever to where a physician who is ordering voriconazole, but there is not a CYP2C19 genotype in the electronic medical record, is sequestered and then sent over to the infectious disease pharmacy team. The physician does not need to be involved with that decision because of the protocols that they've put in place. It allows them to then know, ‘Do I go to an alternate antifungal, or do I wait and get a genotype for this patient?’ And that's very much on the pharmacy side of the equation. So we're able to pick up areas that don't need to be handled by that physician at that time and let it be handled by the pharmacy team there. So instead of seeing this, I guess, in that turf war analogy, this is a handoff to really spread the load so that we're all carrying more of the weight, and it's not being focally put on one profession.

Pharmacy Times: Do you have any closing thoughts?

Nelson: I think the STRIPE mission is to pull people together and to come to—regardless of your standpoints—participate and give your input, and even if it's one of disagreement, embrace the fact that we are trying to embrace being sometimes wrong in order to become more right. In the case of pharmacogenetics, there's always something that we could be doing better and have a better understanding of, and the more people that we have involved with critical thought on that matter, the better a solution we typically come out with. So, to pharmacists, and not just pharmacists—all clinicians—join and participate and help move the dial.