Brian Decker MD, PharmD, MS November 1st, 2016 Pharmacists and pharmacogenomics: A scalable and sustainable strategy for clinical implementation Brian Decker MD, PharmD, MS November 1st, 2016

Outline Why start a pharmacist-managed clinical pharmacogenomic service? Who can we learn from? Staying ahead of progress Discussion…

Why a pharmacist-managed clinical pharmacogenomic service? Pharmacists are the “drug experts” No other health professional has a more complete and encompassing understanding of pharmacology and pharmacotherapy Training in pharmacokinetics, pharmacodynamics and therapeutic drug monitoring provides unique expertise Adverse drug event analysis Drug-drug interactions Expertise in drug information dissemination and clinical education Clinical pharmacogenomics is a natural and logical extension of their already well-established and respected skill-set

Why a pharmacist-managed clinical pharmacogenomic service? What do pharmacists think about the role of clinical pharmacogenomics? Survey of 264 practicing Canadian pharmacists was conducted in 2013 Included all pharmacy practices Predominant community pharmacies (59.4%) Hospital pharmacies also well represented (27.9%) Pharmacogenomics, 2013; 14(2): 165-75.

Pharmacists’ attitudes about clinical pharmacogenomics…

Pharmacists’ hopes about clinical pharmacogenomics… Most pharmacists are “moderately hopeful” PGEN testing will prevent their patient from taking the wrong medicine or dose PGEN testing will allow detection of which drug or dose will be more efficacious PGEN testing will allow detection of which drug or dose will cause less side effects

Pharmacists’ attitudes about clinical pharmacogenomics… Other survey findings… Large majority of responders (96.6%) indicated that they would like to undertake continuing education training on pharmacogenomics Most popular was e-learning (69.9%) Intensive one-weekend training session (50.4%) Several week course (24.6%) Pharmacists were most interested in learning the current availability of pharmacogenomic tests (97.7%), followed by: Interpretation of pharmacogenomics tests (96.5%) Current and future application of pharmacogenomic tests (91.9%) Pharmacogenomics of selected diseases (81.8%) Ethical considerations (67.1%) Basic genetics (63.2%) So, all in all, we have a receptive audience in pharmacists

National Support for Pharmacist Engagement in Clinical Pharmacogenomics Pharmacists competencies in pharmacogenomics was first created and endorsed by the American Academy of Colleges of Pharmacy in 2002 In 2011, the National Human Genome Research Institute convened a large consortium of pharmacy-related organizations and thought leaders to discuss the evolving needs and education gaps in pharmacogenomics for pharmacists A detailed plan was developed to update the competencies that focused on achieving functional knowledge of pharmacogenomics for all pharmacists

National Support for Pharmacist Engagement in Clinical Pharmacogenomics In 2012 a group of 10 pharmacy or pharmacy-related organizations met and endorsed a set of 15 competencies regarding pharmacists and pharmacogenomics

National Support for Pharmacist Engagement in Clinical Pharmacogenomics Outcome statement…

National Support for Pharmacist Engagement in Clinical Pharmacogenomics “Pharmacist-specific knowledge necessary to achieve competencies outcomes are focused on 4 key areas” Basic Genetic Concepts Genetics and Disease Pharmacogenetics/Pharmacogenomics Ethical, Legal and Social Implications

ASHP Statement on the Pharmacist’s Role in Clinical Pharmacogenomics “Pharmacists’ Responsibilities” Advocating for the rational and routine use of pharmacogenomics testing Providing test result interpretation and clinical guidance for return of results to providers and patients in collaboration with other health care professionals Optimizing medication therapy based on pharmacogenomics test results Educating and providing information on the clinical application of pharmacogenomics to health professionals, patients and members of the public Supporting and participating in research, consortia and networks that guide and accelerate the application of pharmacogenomics to clinical practice Am J Health Sys Pharm, 2015; 72(7): 579-81.

Who can we learn from?

St. Jude Children’s Research Hospital Experience 78-bed inpatient facility Planning for inpatient pharmacist-managed clinical PGEN service began in 2005 TPMT (thiopurines) UGT1A1 (irinotecan) CYP2D6 added in 2007 (codeine) IT platform was CernerTM with CDS Am J Health Sys Pharm, 2011; 68: 143-150.

St. Jude Children’s Research Hospital Experience Steps taken to implement a clinical pharmacogenomic service Identified drugs on formulary that are metabolized by polymorphic enzymes Provided a series of ACPE-accredited seminars for pharmacists to establish competencies in pharmacogenomic consults Created a departmental policy to provide direction to pharmacists and laboratory staff in the ordering and reporting of pharmacogenomic test results Communicated the availability of tests to clinical staff

St. Jude Children’s Research Hospital Experience Of 66 patients genotyped for TPMT in 2009, 5 (8%) had one variant allele For CYP2D6, 49 (75%) of the patients were determined to be extensive metabolizers, 9 (14%) intermediate and 4 (6%) were poor metabolizers UGT1A1 has been less useful for irinotecan dosing, but is used clinically to diagnose Gilbert’s Syndrome which helps rule out drug-related toxicity

St. Jude Children’s Research Hospital Experience Success of St. Jude’s pharmacist-managed clinical PGEN service depended upon Collaboration between clinical laboratory and pharmacists Oversight by Clinical Pharmacogenetics Service Steering Committee Well-designed education programs for pharmacists on clinical pharmacogenetics

Boston Children’s Hospital Experience 380- bed stand-alone, quarternary care pediatric hospital Clinical Pharmacogenomics Service (CPS) In-patient service created to facilitate pharmacogenomic information into medical management to promote safer medication use Service is directed by a pharmacist and provide consultations for the clinicians who request assistance with interpretation/application of PGEN data Service is managed by an Oversight Committee Composed of clinical experts who ensure safe and rational movement of drug/gene pairs and return of results to the EMR Manzi, S, Pharmacy Practice Model Initiative: Introducing pharmacogenomics into a pharmacy practice model, Boston Children’s Hospital, Boston MA

Boston Children’s Hospital Experience CPS went live on August 1, 2012 Service included a pharmacogenetics specialty lab view and a consult note structure First drug/gene pair moved into the EMR was thiopurines/TPMT Created the decision support rules that fire on order entry for the three thiopurine derivatives: 6-mercaptopurine, azathiopurine, 6-thioguanine when the patient has a variant status of heterozygous or homozygous deficient All pharmacists received introductory training on the service and the utilization of PGEN data in dosing of the thiopurines Several pharmacists also completed additional competencies to serve as PGEN consultants CPS Oversight Committee plans to move additional drug/gene pairs to the EMR in the future

Boston Children’s Hospital Experience Return on investment 84 TPMT samples run at a cost of $55,200 In-house assay saved $19,000 Nine samples (10.7%) returned with a variant requiring dosage adjustment Without dose adjustment expected ADE is myelosuppression Average length of stay (no ICU) for an ADE is four days Estimate of total cost of four-day hospital stay as high as $126,000 Net savings of avoiding ADE is estimated at $70,800 from this single drug/gene pair

Boston Children’s Hospital Experience Key elements for success Good working relationship with all invested parties Hospital leadership, the genetic testing diagnostic lab, the informatics department, the pharmacy department and the key medical service(s) affected must be part of the process Establish a multidisciplinary oversight committee with a reporting hierarchy is essential Responsible for which drug/gene pairs are the most suited for the institution based on published guidelines, clinical utility and volume Also, responsible for weighing implications of returning the genetic data to the EMR and what level of guidance to provide to the front-line clinicians “Start with something small and manageable and build it all the way from beginning to end”

Staying ahead of progress… Admittedly, this is a longer, but much needed view… Ultimately, pharmacogenetic testing will become standard of care and not be confined to just the framework of a study We need to establish a sustainable system that will be both robust and nimble for this eventuality Key questions for discussion… How do we proactively manage for this growth with our current structure? If a pharmacist-managed pharmacogenomic consult service isn’t the answer, then what is?

Brian Decker MD, PharmD, MS Indiana University School of Medicine Division of Nephrology 950 West Walnut St., R2-202 Indianapolis, IN 46202 (317) 278-2868 bsdecker@iu.edu