Challenges and lessons learned from clinical pharmacogenetic implementation of multiple gene-drug pairs across ambulatory care settings.

PURPOSE: Incorporating a patient's genotype into the clinical decision-making process is one approach to precision medicine. The University of Florida (UF) Health Precision Medicine Program is a pharmacist-led multidisciplinary effort that has led the clinical implementation of six gene-drug(s) pairs to date. This study focuses on the challenges encountered and lessons learned with implementing pharmacogenetic testing for three of these: CYP2D6-opioids, CYP2D6/CYP2C19-selective serotonin reuptake inhibitors, and CYP2C19-proton pump inhibitors within six pragmatic clinical trials at UF Health and partners. METHODS: We compared common measures collected within each of the pharmacogenetic implementations as well as solicited feedback from stakeholders to identify challenges, successes, and lessons learned. RESULTS: We identified several challenges related to trial design and implementation, and learned valuable lessons. Most notably, case discussions are effective for prescriber education, prescribers need clear concise guidance on genotype-based actions, having genotype results available at the time of the patient-prescriber encounter helps optimize the ability to act on them, children prefer noninvasive sample collection, and study participants are willing to answer patient-reported outcomes questionnaires if they are not overly burdensome, among others. CONCLUSION: The lessons learned from implementing three gene-drug pairs in ambulatory care settings will help shape future pharmacogenetic clinical trials and clinical implementations.

Multi-site investigation of strategies for the clinical implementation of CYP2D6 genotyping to guide drug prescribing.

PURPOSE: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers. METHODS: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Data were collected on testing approaches, return of results procedures, applications of genotype results, challenges faced, and lessons learned. RESULTS: Among early adopters, CYP2D6 testing was most commonly ordered to assist with opioid and antidepressant prescribing. Key differences among programs included test ordering and genotyping approaches, result reporting, and clinical decision support. However, all sites tested for copy-number variation and nine common variants, and reported results in the medical record. Most sites provided automatic consultation and had designated personnel to assist with genotype-informed therapy recommendations. Primary challenges were related to stakeholder support, CYP2D6 gene complexity, phenotype assignment, and sustainability. CONCLUSION: There are specific challenges unique to CYP2D6 testing given the complexity of the gene and its relevance to multiple medications. Consensus lessons learned may guide those interested in pursuing similar clinical pharmacogenetic programs.

Pharmacogenomics competencies in pharmacy practice: A blueprint for change.

The emerging use of genomic data to inform medication therapy populates the medical literature and provides evidence for guidelines in the prescribing information for many medications. Despite the availability of pharmacogenomic studies, few pharmacists feel competent to use these new data in patient care. The first pharmacogenomics competency statement for pharmacists was published in 2002. In 2011, the Pharmacogenomics Special Interest Group of the American Association of Colleges of Pharmacy led a process to update this competency statement with the use of a consensus-based method that incorporated input from multiple key professional pharmacy organizations to reflect growth in genomic science as well as the need for pharmacist application of genomic data. Given the rapidly evolving science, educational needs, and practice models in this area, a standardized competency-based approach to pharmacist education and training in pharmacogenomics is needed to equip pharmacists for leadership roles as essential members of health care teams that implement clinical utilization strategies for genomic data.

A stepwise approach to implementing pharmacogenetic testing in the primary care setting.

Pharmacogenetic testing can help identify primary care patients at increased risk for medication toxicity, poor response or treatment failure and inform drug therapy. While testing availability is increasing, providers are unprepared to routinely use pharmacogenetic testing for clinical decision-making. Practice-based resources are needed to overcome implementation barriers for pharmacogenetic testing in primary care.The NHGRI's IGNITE I Network (Implementing GeNomics In pracTicE; www.ignite-genomics.org) explored practice models, challenges and implementation barriers for clinical pharmacogenomics. Based on these experiences, we present a stepwise approach pharmacogenetic testing in primary care: patient identification; pharmacogenetic test ordering; interpretation and application of test results, and patient education. We present clinical factors to consider, test-ordering processes and resources, and provide guidance to apply test results and counsel patients. Practice-based resources such as this stepwise approach to clinical decision-making are important resources to equip primary care providers to use pharmacogenetic testing.

Effects of Using Personal Genotype Data on Student Learning and Attitudes in a Pharmacogenomics Course.

Objective. To evaluate the impact of personal genotyping and a novel educational approach on student attitudes, knowledge, and beliefs regarding pharmacogenomics and genomic medicine. Methods. Two online elective courses (pharmacogenomics and genomic medicine) were offered to student pharmacists at the University of Florida using a flipped-classroom, patient-centered teaching approach. In the pharmacogenomics course, students could be genotyped and apply results to patient cases. Results. Thirty-four and 19 student pharmacists completed the pharmacogenomics and genomic medicine courses, respectively, and 100% of eligible students (n=34) underwent genotyping. Student knowledge improved after the courses. Seventy-four percent (n=25) of students reported better understanding of pharmacogenomics based on having undergone genotyping. Conclusions. Completion of a novel pharmacogenomics elective course sequence that incorporated personal genotyping and genomic medicine was associated with increased student pharmacist knowledge and improved clinical confidence with pharmacogenomics.

Educational strategies to enable expansion of pharmacogenomics-based care.

PURPOSE: The current state of pharmacogenomics education for pharmacy students and practitioners is discussed, and resources and strategies to address persistent challenges in this area are reviewed. SUMMARY: Consensus-based pharmacist competencies and guidelines have been published to guide pharmacogenomics knowledge attainment and application in clinical practice. Pharmacogenomics education is integrated into various pharmacy school courses and, increasingly, into Pharm.D. curricula in the form of required standalone courses. Continuing-education programs and a limited number of postgraduate training opportunities are available to practicing pharmacists. For colleges and schools of pharmacy, identifying the optimal structure and content of pharmacogenomics education remains a challenge; insufficient numbers of faculty members with pharmacogenomics expertise and the inadequate availability of practice settings for experiential education are other limiting factors. Strategies for overcoming those challenges include providing early exposure to pharmacogenomics through foundational courses and incorporating pharmacogenomics into practice-based therapeutics courses and introductory and advanced pharmacy practice experiences. For practitioner education, online resources, clinical decision support-based tools, and certificate programs can be used to supplement structured postgraduate training in pharmacogenomics. Recently published data indicate successful use of "shared curricula" and participatory education models involving opportunities for learners to undergo personal genomic testing. CONCLUSION: The pharmacy profession has taken a leadership role in expanding student and practitioner education to meet the demand for increased pharmacist involvement in precision medicine initiatives. Effective approaches to teaching pharmacogenomics knowledge and driving its appropriate application in clinical practice are increasingly available.

The IGNITE network: a model for genomic medicine implementation and research.

BACKGROUND: Patients, clinicians, researchers and payers are seeking to understand the value of using genomic information (as reflected by genotyping, sequencing, family history or other data) to inform clinical decision-making. However, challenges exist to widespread clinical implementation of genomic medicine, a prerequisite for developing evidence of its real-world utility. METHODS: To address these challenges, the National Institutes of Health-funded IGNITE (Implementing GeNomics In pracTicE; www.ignite-genomics.org ) Network, comprised of six projects and a coordinating center, was established in 2013 to support the development, investigation and dissemination of genomic medicine practice models that seamlessly integrate genomic data into the electronic health record and that deploy tools for point of care decision making. IGNITE site projects are aligned in their purpose of testing these models, but individual projects vary in scope and design, including exploring genetic markers for disease risk prediction and prevention, developing tools for using family history data, incorporating pharmacogenomic data into clinical care, refining disease diagnosis using sequence-based mutation discovery, and creating novel educational approaches. RESULTS: This paper describes the IGNITE Network and member projects, including network structure, collaborative initiatives, clinical decision support strategies, methods for return of genomic test results, and educational initiatives for patients and providers. Clinical and outcomes data from individual sites and network-wide projects are anticipated to begin being published over the next few years. CONCLUSIONS: The IGNITE Network is an innovative series of projects and pilot demonstrations aiming to enhance translation of validated actionable genomic information into clinical settings and develop and use measures of outcome in response to genome-based clinical interventions using a pragmatic framework to provide early data and proofs of concept on the utility of these interventions. Through these efforts and collaboration with other stakeholders, IGNITE is poised to have a significant impact on the acceleration of genomic information into medical practice.