Implementing Pharmacogenomics at Your Institution: Establishment and Overcoming Implementation Challenges

With advancements in pharmacogenomics research and genotyping technology, implementation of pharmacogenomics into clinical practice is now feasible. The aim of this publication is to serve as a tutorial for institutions interested in developing pharmacogenomics services. Topics covered include resources needed, clinical decision support establishment, choosing a genotyping platform, and challenges faced with pharmacogenomics service implementation. This tutorial provides practical advice, drawing upon experience of two established clinical pharmacogenomics services. Clinical characteristics, such as age, body weight, and renal and liver function, have long been used by clinicians to inform drug selection and dosing in clinical practice. Despite this practice, variability in medication response (including lack of efficacy and adverse events) is still commonly observed in patients. The effect of an individual's genomic profile on his/her drug response, or pharmacogenomics (PGx), is thought to predict between 20% and 95% of response variability, depending on the drug.1-4 Thus, combining genetic information with clinical data is an intervention that may improve the safety and effectiveness of medication therapy. Although the benefit of using PGx data to optimize medication therapy is recognized by major stakeholders in the healthcare system, including patients, healthcare professionals, and healthcare insurers,5 its integration into routine clinical practice has been relatively slow compared with the pace of advancement in PGx knowledge and genotyping technology. A number of medical centers in the United States have implemented clinical PGx services in recent years.6-18 The genotyping methods used by these services can be categorized into two groups: (i) preemptive clinical genotyping; and (ii) reactive clinical genotyping. Preemptive clinical genotyping likely represents the most efficient method of PGx data utilization, as genotypes for multiple prespecified variations related to several medications are measured simultaneously. Genetic information is stored in the electronic health record (EHR) and can be used when patients are started on drugs where this information would be helpful. Because of the economies of scale used in preemptive genotyping, the overall cost to genotype variants in many genes simultaneously may be lower than the cost to test variants in each gene individually. On the other hand, reactive genotyping tests focus on the specific variation(s) related to the drug being started at that time. A single test can often be run sooner than a larger preemptive genotyping panel, which are often run in batches to remain cost-competitive. Because of the issues faced with incorporating numerous PGx results (currently actionable vs. potentially actionable in the future) into the EHR, the reduced likelihood of insurance reimbursement, and the large startup costs associated with preemptive genotyping, reactive genotyping might be a more feasible method to use when starting clinical PGx implementation, especially in institutions with limited personnel and financial support. In President Obama's State of the Union address in January 2015, he announced the Precision Medicine Initiative, which will focus on prevention and treatment approaches that account for interindividual variability in drug response, which largely includes PGx. Although the majority of institutions that are currently implementing clinical PGx services in the United States are large academic medical centers, the Precision Medicine Initiative may signal it is time for other institutions to consider implementing as well. Thus, we have created a tutorial for interested clinicians that discuss various approaches to implementing a reactive clinical PGx service, including selection of gene-drug pairs, administrative considerations, and data collection, along with insight and practical advice from two established clinical PGx services at the University of Illinois at Chicago (UIC) and University of Florida (UF) medical centers. Basic PGx concepts have previously been reviewed,19-22 and may provide a useful background for those needing it. Other resources available to enhance education on genomic competencies include Global Genetics and Genomics Community (http://g-3-c.org/en) and the National Institutes of Health (NIH) Genetics/Genomics Competency Center (http://g-2-c-2.org//). Before assessing the capabilities and preparedness of the institution's facilities and personnel, a first gene-drug pair must be identified for implementation. Ideally, the gene(s) being tested would provide information relating to the drug's safety or efficacy, and should be chosen with a target group of patients in mind. At this point, a physician champion is key in advocating for specific gene-drug pairs to implement. Early selection of the initial gene-drug pair(s) will aid in the development of a framework for PGx service implementation. Several factors must be considered when selecting which gene-drug pair(s) to implement. First, the PGx test must have enough evidence to support its clinical utility. Gene-drug pairs with evidence-based guidelines, such as those issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC), and with clear clinical recommendations make good candidates. Second, it is important to implement a PGx test that is relevant to the institution's patient population with regard to frequency of variation within the selected gene(s). 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