Challenges and Solutions for Future Pharmacy Practice in the Era of Precision Medicine

Conference Description

The conference objectives were to gather clinical and research experts across different pharmaceutical areas to discuss key aspects of precision therapy and engage researchers, educators, and health care professionals in these discussions. The conference provided an invaluable opportunity for licensed pharmacists to learn about cutting-edge research and technologies within the field and allowed the option to earn 11 continuing education (CE) units.

A diverse group of 21 speakers contributed to this conference and provided their perspective, including 11 affiliated with UNC, six from outside academic institutions, three from the pharmaceutical industry, and one from the FDA. The speakers were organized into four distinct topic-sessions and covered 10 major themes (Figure 1). More than 200 individuals attended the conference with approximately half affiliated with UNC and the remaining affiliated with industry, clinical practice, or other academic institution. The majority (95%) of attendees were residents of North Carolina and 101 (49%) registered with a pharmacy license number. A poster session consisting of 18 posters and four featured presentations of top abstract submissions allowed researchers to highlight current findings in the field of precision medicine.

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Figure 1.

The 10 major topics that were discussed at the Pharmaceutical Sciences conference.

One major learning tool offered to attendees prior to the conference was pharmacogenomic (PGx) testing with DNA2Rx, a new assay recently developed by the UNC Center for Pharmacogenomics and Individualized Therapy. The test provides extensive information for 18 genes of pharmacogenetic relevance, and the results from this testing were discussed during the conference in an effort to engage attendees in active learning of PGx information with their own personal genetic information.

The first session was focused on pharmacogenomics in precision medicine. PGx is an increasingly important component of the precision medicine field and will be critical for pharmacists because many medications can be optimized for individual genetic differences to achieve improved drug efficacy and reduce unwanted side effects. As PGx research continues to advance, the regulatory aspect, especially in light of new genomic technologies such as next-generation sequencing, will be responsible for developing guidance documents for proper PGx incorporation into the clinical workflow. Guidance documents are currently available for PGx data submissions with additional ones being developed for handling next generation sequencing diagnostic tests. The U.S. Food and Drug Administration (FDA) has approved 187 drug labels across various therapeutic areas that incorporate PGx information.¹⁰ Interpreting PGx information and understanding the impact it has on patient outcomes will become a vital competency for pharmacists and physicians as more PGx efforts are piloted and major bioinformatics implementation challenges are addressed to progress the implementation of genomic information clinically.^11,12

Given this uptake in incorporating genomic information in drug prescribing and the growing consumer demand for better drug therapies, a major focus of this session was exposing conference attendees to basic concepts in this area. PGx information for the drugs with FDA approval was presented in report form for a virtual patient (Figure 2). A subset of the participants (77 or 37.5% of attendees) who elected to receive personal PGx results with DNA2Rx received their own personal PGx information to interpret. An additional 20 individuals signed up for PGx testing after this session. Incorporating PGx information in drug dosing will become a required skill for pharmacists as its use has increased. One way to ensure proper training among practicing pharmacists is to provide PGx testing during training programs to engage students in experiential, active learning. Ideally, key concepts introducing students to PGx should be offered at the undergraduate level and then more comprehensive PGx training should be available to trainees and other health care professionals, as is provided to UNC PharmD students. This way, pharmacists will begin practice with adequate PGx training, and CE programs can focus on more advanced PGx topic areas. Until then, it will be important for CE programs and other educational efforts to be available for pharmacists to gain the basic training in this area.

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Figure 2.

Pharmacogenomic Report Card. The result of the pharmacogenomic assay, DNA2Rx, for a virtual patient is encoded in the quick response (QR) code, which can be scanned (ie, smart phone applications, scanners, etc.) to view pharmacogenomic results and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The report is the size of a business card to allow patients to carry and access their results conveniently.

The second session discussed novel pharmacologic and phenotypic approaches to precision medicine. As technology and research advance in pharmaceutical sciences and medicine, many other pharmacological methodologies within precision medicine are being developed with great promise for clinical application and therapeutic outcomes. One of the challenges is the ability to determine which biomarkers and technologies are most informative or applicable to patient care.

This session focused on three emerging novel approaches to precision medicine that will likely be incorporated into the standard of care in the future. These include using the following phenotypic approaches: adoptive T cell therapy, the microbiome, and metabolomics. Technologies that specifically deliver drug to their intended targets have been a popular area of ongoing research, especially for diseases such as cancer that can be particularly difficult to treat in the clinic as a result of patient-specific differences. The approach described at this conference leverages inherent mechanisms of the immune system to target cancerous cells, such as the ability of T cells to distinguish between healthy and cancerous cells.¹³ Patient-specific characteristics that alter drug metabolism can also improve drug efficacy. The intestinal microbiome, which displays considerable inter-individual differences, is one such characteristic.

The second talk in this session discussed the identification of host factors that significantly alter the intestinal microflora and how these differences can be manipulated to enhance drug response. Technologies that allow users the ability to self-monitor numerous aspects of their lifestyle (eg, diet, exercise, medication) will be imperative in capturing a holistic understanding of the factors that influence interactions of the gut microbiome and drug response.

The last phenotypic approach discussed in this session was metabolomics, and a systems approach in understanding human disease and drug effects as these profiles are shaped by genetics, diet, environmental factors, and the gut microbiome. Metabolomics offers an in-depth understanding of the metabolic pathways that are perturbed in disease and may provide key insight into the underlying nuances in drug response that exist among individuals with the same disease diagnosis. Distinct forms of a disease can be characterized using the metabolome along with profiling responders and non-responders to drugs.¹⁴ Although the topics presented here were unique from one another, they demonstrate that many different approaches may be used to individualize drug therapies in the future. While many of these advances are still exploratory, it is incumbent on pharmacists to keep abreast of the rapidly changing approaches to precision therapy, with the expectation of comprehending and integrating data from these disparate fields into pharmacy practice. Although some of these methods are not yet actively incorporated into clinical practice, ensuring education programs at all levels (eg, undergraduate, professional graduate, and graduate), incorporating some degree of exposure (ie, seminars, electives, etc.) to help familiarize students with these promising areas of precision therapy will be critical. Making these topics available through CE programs will encourage current pharmacists to stay current with the changing landscape of research.

The third session focused on the role of quantitative clinical pharmacology in delivering precision medicine. Another area where precision medicine is progressing to improve the efficacy of drugs and maximize time spent within a drug’s therapeutic range is by individualizing drug dosing using pharmacometric techniques.^15,16 The standard approach to developing drug dosing guidelines has always been based on clinical trial data, which comes from selected and restricted patient groups. This does not provide adequate guidance for individualizing dosing for those members of the population that do not fit within the clinical trial restrictions, and is especially important for drug dosing in special populations (ie, pediatric populations, the elderly, pregnant women).

This session emphasized moving away from the current paradigm of using drug dosing for the “average” patient population to one that incorporates data on real-time drug concentrations and prospectively using pharmacometric tools (ie, population modeling, pharmacokinetic/pharmacodynamic (PK/PD) modeling) to individualize drug dosing. These powerful modeling tools have the potential to achieve appropriate drug target ranges using multiple data inputs, and were demonstrated in a prospective, randomized study conducted with tacrolimus using the BestDose software.¹⁷ Incorporating these pharmacometric tools into the electronic medical records and leveraging existing patient information to inform these models are needed to optimize drug dosing. Several techniques during this session were discussed, including systems engineering feedback control, Bayesian adaptive control, and therapeutic drug monitoring (TDM). More prospective studies, cost-effectiveness analyses, and validated models in this area will facilitate better incorporation into the drug development process and clinical care workflow.¹⁸ Refinement and advancements are expected in this area, and future drug dosing may follow a completely different model than what is used today. The solutions in this session provided guidance for scientific and research challenges related to precision dosing for all patients. Pharmaceutical sciences programs at the graduate level should encourage the curriculum to incorporate new modeling techniques in coursework to help trainees incorporate these elements in their research and help advance efforts in this area.

The last session focused on the implementation of precision therapy. As discussed above, traditional “one-size-fits all” drug development was designed to discover treatments for the “average patient.” Research techniques and study designs will need to be altered from these traditional approaches to gather pertinent data that is unique to help advance the precision medicine field.

The goal of this session was to delve deeper into key aspects of precision medicine research that will help achieve eventual implementation in the clinical setting. Several study designs were discussed, including the N-of-1 studies, drug matching trials, and rapid learning systems. These study design strategies provide a more detailed and adaptive methodology in the research process to better individualize drug treatments for patients. For instance, the N-of-1 study design features a patient as the unit of observation instead of large cohorts, gathering more in-depth information to determine the optimal medical treatment at the individual level.¹⁹ For the genomic field, one challenge in conducting precision medicine research to find the genomic underpinnings of a particular phenotype is gaining access to adequate cohort sizes. Collaborations, especially among academia, health care, and industry, will be vital in being able to identify these cohorts. For example, 23andMe (https://www.23andme.com/) has genetic and phenotype information for more than two million participants, which can be leveraged to study a particular phenotype of interest. Access to such a large cohort has resulted in numerous collaborations with pharmaceutical companies and academic institutions to identify genetic markers pertinent in the development of therapeutics and in the understanding of diseases. Another key stakeholder group who influences the implementation of precision medicine in the clinical setting are health care payers. Coverage and reimbursement for PGx testing and procedures are vital for successful uptake and clinical use of precision medicine. Payers have their own set of requirements when providing favorable coverage, including demonstrating the cost-effectiveness of PGx tests.²⁰ Pharmaceutical science programs at the undergraduate and graduate level can incorporate information from this section into the curriculum to expose students to more individualized research study designs and these concepts can be further reinforced through coursework or journal clubs. Seminars and professional events are also a valuable opportunity for trainees to gain exposure and engage with private companies and health care payers.

Evaluations from the Attendees

Attendees receiving CE units from the conference were required to fill out a survey that evaluated the program, and the responses received represent approximately half of the attendees. These attendees had an overwhelmingly positive response to the conference. For these three statements from the survey: the content of the programming met your educational needs and goals, the program enhanced my knowledge or skills, and the speaker was knowledgeable; greater than 90% responded with strongly agreed or agreed. When asked “how will you use this information in your practice,” most free-response answers related to improving care provided to patients in practice, proposing or advocating for genomic testing at a clinical site, including precision medicine in research efforts, and updating current educational materials being taught at institutions to include precision medicine. Other features of the conferences that were cited as valuable include the pharmacogenomic reports that improved engagement, the discussion of precision medicine beyond genomics, and the various perspectives that were presented (ie, regulatory, private companies, insurance companies, academia, etc.). Table 1 provides more detailed results from the survey data. Suggestions for future programming included academic drug development, a focused therapeutic area within precision medicine, and more workshops on precision medicine.