Amanda R. Elsey

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.

Institutional Profile: University of Florida and Shands Hospital Personalized Medicine Program: clinical implementation of pharmacogenetics

The University of Florida and Shands Hospital recently launched a genomic medicine program focused on the clinical implementation of pharmacogenetics called the Personalized Medicine Program. We focus on a pre-emptive, chip-based genotyping approach that is cost effective, while providing experience that will be useful as genomic medicine moves towards genome sequence data for patients becoming available. The Personalized Medicine Program includes a regulatory body that is responsible for ensuring that evidence-based examples are moved to clinical implementation, and relies on clinical decision support tools to provide healthcare providers with guidance on use of the genetic information. The pilot implementation was with CYP2C19–clopidogrel and future plans include expansion to additional pharmacogenetic examples, along with aiding in implementation in other health systems across Florida.

The Pharmacogenomics Research Network Translational Pharmacogenetics Program: Outcomes and Metrics of Pharmacogenetic Implementations Across Diverse Healthcare Systems

Numerous pharmacogenetic clinical guidelines and recommendations have been published, but barriers have hindered the clinical implementation of pharmacogenetics. The Translational Pharmacogenetics Program (TPP) of the National Institutes of Health (NIH) Pharmacogenomics Research Network was established in 2011 to catalog and contribute to the development of pharmacogenetic implementations at eight US healthcare systems, with the goal to disseminate real‐world solutions for the barriers to clinical pharmacogenetic implementation. The TPP collected and normalized pharmacogenetic implementation metrics through June 2015, including gene–drug pairs implemented, interpretations of alleles and diplotypes, numbers of tests performed and actionable results, and workflow diagrams. TPP participant institutions developed diverse solutions to overcome many barriers, but the use of Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provided some consistency among the institutions. The TPP also collected some pharmacogenetic implementation outcomes (scientific, educational, financial, and informatics), which may inform healthcare systems seeking to implement their own pharmacogenetic testing programs.

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.

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.

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.

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.