Current practices in the delivery of pharmacogenomics: Impact of the recommendations of the Pharmacy Practice Model Summit.

PURPOSE: This report examines and evaluates pharmacogenomics as an emerging science as it relates to the Practice Advancement Initiative and its predecessor the Pharmacy Practice Model Initiative's consensus statements for optimal pharmacy practice models. SUMMARY: Pharmacogenomics is one of many emerging sciences to impact medication management and delivery of patient care. Increasingly, biomarkers are included in drug labeling and can assist pharmacists with personalizing medicine to optimize patient therapies and avoid adverse effects. The 2011 ASHP Pharmacy Practice Model Summit generated a list of 147 consensus statements for optimal pharmacy practice. Of these, 1 statement explicitly describes adjustment of drug regimens based on genetic factors as an essential activity of pharmacist-provided drug regimens, and 9 other statements provide additional support for incorporation of this emerging science into all aspects of patient care provided by pharmacists. We describe 4 institutions that have made significant inroads to implementing pharmacogenomics, to provide a framework and serve as resources for other institutions initiating their own pharmacogenomics implementation journeys. CONCLUSION: Through prioritized efforts of the pharmacy profession and health care institutions, pharmacogenomics will be disseminated and implemented, and the goal of the Pharmacy Practice Model Initiative's consensus statements of improving health care using patients' genetic characteristics will be realized.

CYP2D6-guided opioid therapy improves pain control in CYP2D6 intermediate and poor metabolizers: a pragmatic clinical trial.

PURPOSE: CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia. This pragmatic proof-of-concept trial tested the effects of CYP2D6-guided opioid prescribing on pain control. METHODS: Participants with chronic pain (94% on an opioid) from seven clinics were enrolled into CYP2D6-guided (n = 235) or usual care (n = 135) arms using a cluster design. CYP2D6 phenotypes were assigned based on genotype and CYP2D6 inhibitor use, with recommendations for opioid prescribing made in the CYP2D6-guided arm. Pain was assessed at baseline and 3 months using PROMIS® measures. RESULTS: On stepwise multiple linear regression, the primary outcome of composite pain intensity (composite of current pain and worst and average pain in the past week) among IM/PMs initially prescribed tramadol/codeine (n = 45) had greater improvement in the CYP2D6-guided versus usual care arm (-1.01 ± 1.59 vs. -0.40 ± 1.20; adj P = 0.016); 24% of CYP2D6-guided versus 0% of usual care participants reported ≥30% (clinically meaningful) reduction in the composite outcome. In contrast, among normal metabolizers prescribed tramadol or codeine at baseline, there was no difference in the change in composite pain intensity at 3 months between CYP2D6-guided (-0.61 ± 1.39) and usual care (-0.54 ± 1.69) groups (adj P = 0.540). CONCLUSION: These data support the potential benefits of CYP2D6-guided pain management.

Physician-Reported Benefits and Barriers to Clinical Implementation of Genomic Medicine: A Multi-Site IGNITE-Network Survey.

Genetic medicine is one of the key components of personalized medicine, but adoption in clinical practice is still limited. To understand potential barriers and provider attitudes, we surveyed 285 physicians from five Implementing GeNomics In pracTicE (IGNITE) sites about their perceptions as to the clinical utility of genetic data as well as their preparedness to integrate it into practice. These responses were also analyzed in comparison to the type of study occurring at the physicians' institution (pharmacogenetics versus disease genetics). The majority believed that genetic testing is clinically useful; however, only a third believed that they had obtained adequate training to care for genetically "high-risk" patients. Physicians involved in pharmacogenetics initiatives were more favorable towards genetic testing applications; they found it to be clinically useful and felt more prepared and confident in their abilities to adopt it into their practice in comparison to those participating in disease genetics initiatives. These results suggest that investigators should explore which attributes of clinical pharmacogenetics (such as the use of simplified genetics-guided recommendations) can be implemented to improve attitudes and preparedness to implement disease genetics in care. Most physicians felt unprepared to use genetic information in their practice; accordingly, major steps should be taken to develop effective clinical tools and training strategies for physicians.

Clinical application of pharmacogenetics in pain management.

There is growing experience translating genomic data into clinical practice, as seen with the Implementing GeNomics In pracTicE (IGNITE) network. A primary example is the influence of CYP2D6 genotype on the beneficial and adverse effects of some opioids. Clinical recommendations exist to guide drug therapy based on CYP2D6 genotype for codeine, tramadol, oxycodone and hydrocodone, although the level of supporting evidence differs by drug. Limited evidence also supports the use of genetic data to guide other medications in chronic pain therapy, including tricyclic antidepressants and celecoxib. Pragmatic clinical trial data are needed in this area to better understand the impact of diverse populations, therapeutic interventions and clinical care environments on genotype-guided drug therapy for chronic pain.

Research Directions in the Clinical Implementation of Pharmacogenomics: An Overview of US Programs and Projects.

Response to a drug often differs widely among individual patients. This variability is frequently observed not only with respect to effective responses but also with adverse drug reactions. Matching patients to the drugs that are most likely to be effective and least likely to cause harm is the goal of effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision medicine through elucidating the genetic determinants responsible for pharmacological outcomes and using them to guide drug selection and dosing. Here we survey the US landscape of research programs in PGx implementation, review current advances and clinical applications of PGx, summarize the obstacles that have hindered PGx implementation, and identify the critical knowledge gaps and possible studies needed to help to address them.

Implementation of Standardized Clinical Processes for TPMT Testing in a Diverse Multidisciplinary Population: Challenges and Lessons Learned.

Although thiopurine S-methyltransferase (TPMT) genotyping to guide thiopurine dosing is common in the pediatric cancer population, limited data exist on TPMT testing implementation in diverse, multidisciplinary settings. We established TPMT testing (genotype and enzyme) with clinical decision support, provider/patient education, and pharmacist consultations in a tertiary medical center and collected data over 3 years. During this time, 834 patients underwent 873 TPMT tests (147 (17%) genotype, 726 (83%) enzyme). TPMT tests were most commonly ordered for gastroenterology, rheumatology, dermatology, and hematology/oncology patients (661 of 834 patients (79.2%); 580 outpatient vs. 293 inpatient; P < 0.0001). Thirty-nine patients had both genotype and enzyme tests (n = 2 discordant results). We observed significant differences between TPMT test use and characteristics in a diverse, multispecialty environment vs. a pediatric cancer setting, which led to unique implementation needs. As pharmacogenetic implementations expand, disseminating lessons learned in diverse, real-world environments will be important to support routine adoption.

Multisite Investigation of Strategies for the Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy.

CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program. Key differences between programs included the test result turnaround time and timing of therapy changes, which are both related to the CYP2C19 testing model and platform used. Sites reported the need for new informatics infrastructure, expert clinicians such as pharmacists to interpret results, physician champions, and ongoing education. Consensus lessons learned are presented to provide a path forward for those seeking to implement similar clinical pharmacogenomics programs within their institutions.

Preemptive Panel-Based Pharmacogenetic Testing: The Time is Now.

While recent discoveries have paved the way for the use of genotype-guided prescribing in some clinical environments, significant debate persists among clinicians and researchers about the optimal approach to pharmacogenetic testing in clinical practice. One crucial factor in this debate surrounds the timing and methodology of genotyping, specifically whether genotyping should be performed reactively for targeted genes when a single drug is prescribed, or preemptively using a panel-based approach prior to drug prescribing. While early clinical models that employed a preemptive approach were largely developed in academic health centers through multidisciplinary efforts, increasing examples of pharmacogenetic testing are emerging in community-based and primary care practice environments. However, educational and practice-based resources for these clinicians remain largely nonexistent. As such, there is a need for the health care system to shift its focus from debating about preemptive genotyping to developing and disseminating needed resources to equip frontline clinicians for clinical implementation of pharmacogenetics. Providing tools and guidance to support these emerging models of care will be essential to support the thoughtful, evidence-based use of pharmacogenetic information in diverse clinical practice environments. Specifically, the creation of efficient and accurate point-of-care resources, practice-based tools, and clinical models is needed, along with identification and dissemination of sustainable avenues for pharmacogenetic test reimbursement.

Institutional profile: University of Florida Health Personalized Medicine Program.

The University of Florida (UF) Health Personalized Medicine Program launched in 2012 with CYP2C19 genotyping for clopidogrel response at UF Health Shands Hospital. We have since expanded CYP2C19 genotyping to UF Health Jacksonville and established the infrastructure at UF Health to support clinical implementation for five additional gene-drug pairs: TPMT-thiopurines, IFNL3 (IL28B)-PEG IFN-α-based regimens, CYP2D6-opioids, CYP2D6/CYP2C19-antidepressants and CYP2C19-proton pump inhibitors. We are contributing to the evidence based on outcomes with genotype-guided therapy through pragmatic studies of our clinical implementations. In addition, we have developed a broad array of educational programs for providers, trainees and students that incorporate personal genotype evaluation to enhance participant learning.

Implementation of inpatient models of pharmacogenetics programs.

PURPOSE: The operational elements essential for establishing an inpatient pharmacogenetic service are reviewed, and the role of the pharmacist in the provision of genotype-guided drug therapy in pharmacogenetics programs at three institutions is highlighted. SUMMARY: Pharmacists are well positioned to assume important roles in facilitating the clinical use of genetic information to optimize drug therapy given their expertise in clinical pharmacology and therapeutics. Pharmacists have assumed important roles in implementing inpatient pharmacogenetics programs. This includes programs designed to incorporate genetic test results to optimize antiplatelet drug selection after percutaneous coronary intervention and personalize warfarin dosing. Pharmacist involvement occurs on many levels, including championing and leading pharmacogenetics implementation efforts, establishing clinical processes to support genotype-guided therapy, assisting the clinical staff with interpreting genetic test results and applying them to prescribing decisions, and educating other healthcare providers and patients on genomic medicine. The three inpatient pharmacogenetics programs described use reactive versus preemptive genotyping, the most feasible approach under the current third-party payment structure. All three sites also follow Clinical Pharmacogenetics Implementation Consortium guidelines for drug therapy recommendations based on genetic test results. CONCLUSION: With the clinical emergence of pharmacogenetics into the inpatient setting, it is important that pharmacists caring for hospitalized patients are well prepared to serve as experts in interpreting and applying genetic test results to guide drug therapy decisions. Since genetic test results may not be available until after patient discharge, pharmacists practicing in the ambulatory care setting should also be prepared to assist with genotype-guided drug therapy as part of transitions in care.

Emerging roles for pharmacists in clinical implementation of pharmacogenomics.

Pharmacists are uniquely qualified to play essential roles in the clinical implementation of pharmacogenomics. However, specific responsibilities and resources needed for these roles have not been defined. We describe roles for pharmacists that emerged in the clinical implementation of genotype-guided clopidogrel therapy in the University of Florida Health Personalized Medicine Program, summarize preliminary program results, and discuss education, training, and resources needed to support such programs. Planning for University of Florida Health Personalized Medicine Program began in summer 2011 under leadership of a pharmacist, with clinical launch in June 2012 of a clopidogrel-CYP2C19 pilot project aimed at tailoring antiplatelet therapies for patients undergoing percutaneous coronary intervention and stent placement. More than 1000 patients were genotyped in the pilot project in year 1. Essential pharmacist roles and responsibilities that developed and/or emerged required expertise in pharmacy informatics (development of clinical decision support in the electronic medical record), medication safety, medication-use policies and processes, development of group and individual educational strategies, literature analysis, drug information, database management, patient care in targeted areas, logistical issues in genetic testing and follow-up, research and ethical issues, and clinical precepting. In the first 2 years of the program (1 year planning and 1 year postimplementation), a total of 14 different pharmacists were directly and indirectly involved, with effort levels ranging from a few hours per month, to 25-30% effort for the director and associate director, to nearly full-time for residents. Clinical pharmacists are well positioned to implement clinical pharmacogenomics programs, with expertise in pharmacokinetics, pharmacogenomics, informatics, and patient care. Education, training, and practice-based resources are needed to support these roles and to facilitate the development of financially sustainable pharmacist-led clinical pharmacogenomics practice models.

Clinical pharmacogenetics implementation: approaches, successes, and challenges.

Current challenges exist to widespread clinical implementation of genomic medicine and pharmacogenetics. The University of Florida (UF) Health Personalized Medicine Program (PMP) is a pharmacist-led, multidisciplinary initiative created in 2011 within the UF Clinical Translational Science Institute. Initial efforts focused on pharmacogenetics, with long-term goals to include expansion to disease-risk prediction and disease stratification. Herein we describe the processes for development of the program, the challenges that were encountered and the clinical acceptance by clinicians of the genomic medicine implementation. The initial clinical implementation of the UF PMP began in June 2012 and targeted clopidogrel use and the CYP2C19 genotype in patients undergoing left heart catheterization and percutaneous-coronary intervention (PCI). After 1 year, 1,097 patients undergoing left heart catheterization were genotyped preemptively, and 291 of those underwent subsequent PCI. Genotype results were reported to the medical record for 100% of genotyped patients. Eighty patients who underwent PCI had an actionable genotype, with drug therapy changes implemented in 56 individuals. Average turnaround time from blood draw to genotype result entry in the medical record was 3.5 business days. Seven different third party payors, including Medicare, reimbursed for the test during the first month of billing, with an 85% reimbursement rate for outpatient claims that were submitted in the first month. These data highlight multiple levels of success in clinical implementation of genomic medicine.

Complete-block scheduling for advanced pharmacy practice experiences.

PURPOSE: An innovative approach to meeting increased student demand for advanced pharmacy practice experiences (APPEs) is described, including lessons learned during a two-year pilot project. SUMMARY: To achieve more efficient allocation of preceptor resources, the University of Florida College of Pharmacy (UFCOP) adopted a new APPE rotation model in which 20 pharmacy students per year complete all required and elective APPEs at one practice site, an affiliated academic medical center. Relative to the prevailing model of experiential training for Pharm.D. students, the "complete-block scheduling" model offers a number of potential benefits to students, preceptors, and the pharmacy school. In addition to potentially reduced student housing expenses and associated conveniences, complete-block scheduling may enable (1) more efficient use of teaching resources, (2) increased collaboration among preceptors, (3) greater continuity and standardization of educational experiences, and (4) enhanced opportunities for students to engage in longer and more complex research projects. The single-site APPE rotation model also can provide value to the training site by enabling the extension of clinical pharmacy services; for example, UFCOP students perform anticoagulation monitoring and discharge medication counseling at the host institution. Despite logistical and other challenges encountered during pilot testing of the new scheduling model, the program has been well received by students and preceptors alike. CONCLUSION: Complete-block APPE scheduling is a viable model for some health systems to consider as a means of streamlining experiential education practices and helping to ensure high-quality clinical rotations for Pharm.D. students.

Teaching clinical problem solving: a preceptor's guide.

PURPOSE: Instructional methods to help pharmacists succeed in their growing role in practice-based teaching are discussed, with an emphasis on techniques for fulfilling the four key preceptor roles. SUMMARY: The American Society of Health-System Pharmacists (ASHP) and other organizations advocate ongoing efforts to develop the teaching skills of clinician-educators serving as preceptors to pharmacy students and residents. The broad model of teaching clinical problem solving recommended by ASHP emphasizes the creative and flexible application of the four major preceptor roles: (1) direct instruction, (2) modeling, (3) coaching, and (4) facilitating. A variety of teaching methods used in the fields of medicine and nursing that can also be adopted by practice-based pharmacy educators are presented; in particular, the advantages and disadvantages of various case-presentation formats (e.g., One-Minute Preceptor, SNAPPS, patient-witnessed teaching, "Aunt Minnie," "think-aloud") are reviewed. Other topics discussed include the appropriate use of questioning as an educational tool, strategies for providing constructive feedback, teaching learners to self-evaluate their skills and progress, and integrating residents into teaching activities. CONCLUSION: The ASHP-recommended approach to teaching clinical problem-solving skills can be applied within the educational frameworks provided by schools of pharmacy as well as pharmacy residency programs. A wide range of validated teaching strategies can be used to tailor learning experiences to individual learner needs while meeting overall program goals and objectives.