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Developing, Implementing, and Sharing Pharmacogenomics CDS

Robert R. Freimuth, Ph.D. Biomedical Statistics and Informatics, Applied Clinical Informatics

AMIA TBI March 18, 2013

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Pharmacogenomics (PGx) CDS

Mayo Clinic PGx CDS Case Study: Abacavir Challenges Challenges for Genomics-Based CDS Sharing Knowledge Standardization Challenges of the Future

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EHR at Mayo Clinic, Rochester

>12 different systems that store primary data GE Started from a partnership with HP in late 1980s Mainframe design Blaze Advisor rule engine Built for large-scale financial applications (FICO) Designed for complex, multi-faceted problems Full forward and backward chaining logic Tightly coupled to data sources

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CDS at Mayo Clinic, Rochester

Developing CDS solutions for >20 years Initially developed over home-grown EHR Batch-oriented rules for events and conditions Standalone systems for different departments
e.g., Pharmacy, Infectious Disease Started using Blaze ~2005 Provided real-time CDS

>100 high-level rules composed of ~1000 atomic rules

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CDS Rule Development Process

Synthesis of clinical knowledge Committee approvals Technical specifications UI screen design Web service calls, database queries Implementation and deployment Compiling Loading to rule servers on mainframe Run modes Silent "Live"
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Abacavir and HLA-B*5701

Abacavir Nucleoside RT-inhibitor for HIV infection HLA-B >1500 known variants *5701 allele is associated with life-threatening
hypersensitivity reactions to abacavir Results are either "positive" or "negative"

At Mayo Clinic, *5701 screening is recommended: Prior to initiating treatment with abacavir Prior to reinitiation of abacavir in patients of
unknown HLA-B*5701 status who have previously tolerated abacavir
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Abacavir-HLA B*5701: Governance

Executive sponsors: Center for Individualized Medicine Pharmacogenomics Task Force Mayo Pharmacy Formulary Committee Disease-Oriented Task Force: ID Other committee approvals: Practice Convergence Council (MC-CPC) MC Clinical Decision Support Subcommittee Implementation Site-based P&T committees, coordinate with CIM Local CDS teams
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Abacavir-HLA B*5701 Workflow

Internal lab result? External lab result? What is it? Prompt for test Capture result Inbox message

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Abacavir-HLA B*5701 Results

Text report MCF, MCA, MCHS Structured data MCR

Storage of results Internal: lab test External: custom table Added as an allergy

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Challenges: Abacavir

Currently using the Allergy model Can be deleted or altered Policy for positive test/deleted allergy Not a true allergy Reaction has not occurred, but is possible Storing external results in a custom table Inaccessible by other systems (e.g., pharmacy) Providers can't see entries from prior admissions

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Challenges: External Results

Capture Streamline current alert-heavy process Representation Test orders and results change over time Storage "Clinical event" (MCF/MCA) "Observation/finding" (MCR) Exchange CDA (partial solution for providers?) Clinical notes (patient-reported data)

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Challenges: Enterprise-Level

Coordination across the Mayo enterprise (multi-site) Group formed to focus on challenges related to the
implementation of PGx CDS Identify issues with our current infrastucture Identify bottlenecks in processes Propose short and long term solutions Consensus for functional requirements Abacavir vs. Carbamazepine

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Challenges: Education

Clinical knowledge Proactive: Videos, articles On-demand: AskMayoExpert (AME) Contextual: Alerts link to AME Rule implementation Consequences of going against recommendation "If the patient has been on abacavir for 10 years,
do I still need to order the test?" Workflow "If I click yes (or no), how many more alerts will pop up?"

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Measuring Outcomes of PGx CDS

Evaluating effectiveness What data should be captured? Case-by-case decision? Increased effectiveness of therapy Decreased adverse reactions or complications Fiscal responsibility Over-testing Time to resolution Increased efficiency of healthcare delivery

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Refining PGx CDS

Create highly specific triggers Limit by drug, genotype Ethnicity? Requires accurate data, not always available Probabilities? Allele, adverse reaction, effective treatment Context-sensitive IL28B, peginterferon, and hepatitis C Timing: diagnosis vs. CPOE

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Increasing Complexity of Genomics CDS

Evolution from "simple" CDS to guided workflows Context-sensitive expert systems Require provider input Prompt for data (e.g., family history) Technical limitations in popup alerts Important for complex decisions Need to capture clinical judgement Not limited to genomics

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Sharing Knowledge

Human-readable text PharmGKB Structured representations TPP/CPIC tables Semantically computable PGx Guideline Repository Implementation-independent algorithms Generalized syntax, metadata Executable code (local adoption)

Tuesday Posters

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Sharing Knowledge Is Hard

Who? Governance Many stakeholders What? Institutional vs. national standards of care Not everything is generalizable Where? Distributed vs. Centralized How? Knowledgebases Code libraries Web services


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Guideline development and interpretation Clinical practice and standard of care Allele definitions (molecular) Nomenclature is only part of the solution Stability Inferrence Phenotype definitions Genotype-phenotype translation Test results Health Sequence vs. interpretation eDecisions CDS rules
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Challenges of the Future

Combinatorial expansion, complexity Gene-Drug / Gene-Drug Class Gene-Gene-Drug / Pathway-Drug Advances in knowledge Stable representation of results Sequence? Interpretation? Reinterpretation process Store updated results Educate providers Advances in technology Merge, reconcile results
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Challenges of the Future

Genome on a thumb drive The ultimate in patient-provided data Patient mobility

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Acknowledgements Abacavir Implementation

Michelle Elliott, MD Joseph Paul, MD David Blair, MD John Black, MD (DLMP) Joseph Yao, MD (DLMP) Robert Freimuth, PhD (Knowledge Engineering) (Knowledge Engineering)

Jyotishman Pathak, PhD Mark Siska, RPh Kelly Wix, DPh

Pedro Caraballo, MD (GIM) Robert Bleimeyer (Blaze, MN) Mark Dobie (Blaze, MN) Padma Rao (Blaze, MN) Liz Clark (Cerner, AZ) Gaurav Jain (Cerner, MCHS) Charles Pugh (Cerner, FL) Cloann Schultz (PM, CIM) Caer Vitek (Education, CIM) Donald Gabrielson (PM) and many others

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