Making Genomic Medicine a Reality for VermontThe heart and science of medicine. Making Genomic...
Transcript of Making Genomic Medicine a Reality for VermontThe heart and science of medicine. Making Genomic...
The heart and science of medicine
Making Genomic Medicine a Reality for VermontDebra GB Leonard MD PhDChair amp Professor Pathology amp Laboratory MedicineRobert Larner MD College of Medicine at UVMUVM Health NetworkBurlington VT
Vermont is the Green Mountain StateldquoUVMrdquo from Latin
Universitas Viridis Montis
bull The Setting
bull My Vision in 2013
bull Genomic Medicine Plan amp Implementation
bull The Future
Outline
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Healthcare in Vermont
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VermontPopulation
626011
UVMMC Burlington
Across Lake Champlain to NY
New York StatePopulation83 Million
New YorkPopulation83 Million
2011 Green Mountain Care Lawbull Improve the health of Vermontersbull Improve quality of healthcarebull Regulate healthcare costs
ndash Hospital budgets (lt35 budget growthyear)ndash Major capital expenditures (CON process) andndash Health insurance rates
bull Approve plans ndash For health insurance benefits in exchange program ndash To recruit and retain health professionals
bull Build amp maintain electronic health information systems
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University of Vermont Health Network
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Affiliation Agreement
UVM Medical CenterPorter HospitalCentral Vermont Medical CenterAlice Hyde Medical CenterChamplain Valley Physicians HospitalElizabethtown Hospital
+ 2 FQHCs =
Vermont Care Organization
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Changing World View
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Fee for Service gtDo = More $
Global Payment lt Do (IF keep people healthy) = More $
2017 30 Medicaid is global payment in Vermont
Molecular Pathology in Vermont
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Human Genome Project 2001Sanger Capillary Electrophoresis Sequencing
Analog
Next Generation Sequencing 2004 $750K
Digital
Next Generation Sequencing 2011
Gene Panelstimes Exometimes Genome
$75K-125K
Low Cost Next Gen InstrumentsDrove Clinical Genomics Forward
Clinical Genomic Medicine Programs in 2012bull ARUP Large gene panel for inflammatory bowel diseasebull Emory X-linked intellectual disabilitybull Illumina Exome analysis in CLIA lab for constitutional diagnosisbull Johns Hopkins Cancer-specific rearrangements for cancer recurrencebull MGH All lung cancers tested for 110 mutations in 13 genesbull Medical College of Wisconsin Exome sequence for inherited
conditionsbull Memorial Sloan-Kettering Cancer Center All lung cancers amp
metastatic colon cancers tested for 164 mutations in 23 genesbull Partners Center for Personalized Genetic Medicine Large gene
panels for cancer cardiomyopathy hearing loss pharmacogenetics connective tissue disorders etc
bull Vanderbilt All lung cancers and melanomas tested with 40 mutation panel
bull Washington University All cancers have complete sequence of 28 genes
bull Yale Exome sequencing for congenital conditions and cancer20
Focus on cancer amp inherited disorders
Predominantly gene panels or exome
MolecularGenomics at UVMMC in 2012
bull Extensive molecularMS microbiologybull Genetics FV FII MTHFR HCRbull Cancer JAK2bull Cytogenetics Karyotyping FISH
Barrier to Molecular Testing at UVMMCWas Low Volume per Test
Reality for Molecular Pathology in Vermont
bull Population 626011bull 35500 Surgical amp 32000 Cytologybull 53M laboratory testsbull Test volume too low to develop
ndash Cancer testing by tissue of originndash Inherited disorder testing by disease
Lower volumes common in much of US
bull The Setting
bull My Vision in 2013
bull Genomic Medicine Plan amp Implementation
bull The Future
Outline
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Molecular Plan for Vermont was Genomics
bull Skip molecular and use genomicsbull Next gen for panels exome genomebull Limited number of genomic testsbull Each test used for many patientsbull Use molecular methods for validations
amp confirmations
UVM Vision Genomes for All
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Genotype Drives Phenotype
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A Genome contains Fundamental Medical Information
Gregrsquos primary care physician
ldquoI would have never pegged you as having FMF
Look at you You have blue eyes and blond hairrdquo
bull Healthcare provider diagnostic ability limited byndash Knowledge-base ndash Biasesndash Time
Accurate Diagnosis Drives Effective Treatment
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Genome results may reduce diagnostic limitations
bull Genome results may identify disease risks before onset of symptomsndash Targeted monitoring only for at risk individualsndash Preventive strategies when available
Disease Risk for Population Health Management
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Neurofibromatosis type 2 EhlersndashDanlos syndrome vascular type Marfan syndrome LoeysndashDietz
syndromes and familial thoracic aortic aneurysms and dissections
Hypertrophic cardiomyopathy dilated cardiomyopathy
Catecholaminergic polymorphic ventricular tachycardia
Arrhythmogenic right-ventricular cardiomyopathy
RomanondashWard long QT syndrome types 1 2 and 3 Brugada syndrome
Familial hypercholesterolemia 143890 Malignant hyperthermia susceptibility
ExomeGenome Reportable Results (ACMG) Hereditary breast and ovarian cancer LindashFraumeni syndrome PeutzndashJeghers syndrome Lynch syndrome Familial adenomatous polyposis MYH-associated polyposis Von HippelndashLindau syndrome Multiple endocrine neoplasia type 1amp2 Familial medullary thyroid cancer PTEN hamartoma tumor syndrome Retinoblastoma Hereditary paraganglioma-
pheochromocytoma syndrome Tuberous sclerosis complex WT1-related Wilms tumor
Genet Med 201315(7)565ndash574
Each Person is Unique
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Genome EnvironmentEpigenome
YOU
+Medical PhenotypeHealthcare Provider (EHR)
Patient
A Genome is a Journey
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Promise of Genomic Medicine
Improve patient outcomes
Improve population health especially for families
Improve cost-effectiveness of care
Genomic Medicine Promisealigns with
Healthcare Reform Goals
Genomic Medicine Program
Genomic Translational
Research
Biobank
Genomic Data
Healthcare Data
Genomic Education
Clinical Genomic Medicine
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Clinical Genomic Medicine
bull The Setting
bull My Vision in 2013
bull Genomic Medicine Plan amp Implementation
bull The Future
Outline
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Genomic Medicine Program
Genomic Translational
Research
Biobank
Genome Databank
Healthcare Databank
Genomic Education
Clinical Genomic Medicine
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Clinical Genomic Medicine
Clinical Genomic Medicine Plan for next 3 to 5 years
Genomic Medicine Clinical Tests
bull Cancer gene panels (25-50 genes)ndash Solid tumor (29 genes) ndash LIVE as of 2116ndash Hematologic malignancy (being validated DNA amp RNA)ndash Inherited cancer risk gene panel
bull Pharmacogenomic gene panel (50-80 genes)bull Inherited disorders (exome or genome)
ndash Specific multigene diseases (eg CV NM disease)ndash Unidentified inherited disorder (eg NICU babies)ndash Over time sequence genome of every person if cost
effectiveIntegrating Tests into Clinical Care Pathways
Genomic Care Pathways
Clinical pathways to integrate genomic testing into patient carendash Identify patients who are appropriate for testingndash Obtain informed consentndash Obtain the right specimenndash Perform genomic test amp interpret in clinical contextndash Integrate genomic results into EHRndash Discuss genomic results at multidisciplinary conferencesndash Counsel patient (amp family) as appropriatendash Test family members with informed consent as indicated
UVM Clinical Genomic Medicine Team
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PARTNERSCardiology
Medical GeneticsOBGYNOncologyPathologyPatients
PediatricsPharmacyRadiology
SurgeryEverybodyhellip
GENOMIC MEDICINE PROGRAMDebra Leonard MD PhD DirectorNiki Sidiropoulos MD Medical DirectorDavid Seward MD PhD AttendingKen Hampel PhD Courtney Scott MT(ASCP)Jordan Armstrong MTMargaret Cameron
BIOINFORMATICSPierianDx
Rakesh Nagarajan MD PhDJulie Dragon PhD
Building the Genomic Medicine Team
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Year People Progress
2013 Debra Leonard MD PhDNiki Sidiropoulos MDCourtney Scott MT(ASCP)
5-Yr Business PlanPierianDX License Decision amp WorkPurchasing
2014 Ken Hampel PhD 5-Yr Business Plan ApprovalIT amp Test Method DesignValidation
2015 Jordan ArmstrongPre-authorization staff
Redo Business Plan and Lab Design (CON)Negotiations with payersGene Panel Solid Tumor Test Validation
2016 David Seward MD PhDMargaret Cameron
Gene Panel Solid Tumor Test Live (DNA)Solid Tumor RNASeq ValidationStart Genomic Oncology TDT
2017 Robert Wildin MDGenetic Counselor
Reflex unresectable CRC Lung amp MelanomasHemepath Gene Panel Design amp Validation
Collaboration for Interpretation
bull Human Genome Project Centerbull Began clinical genomics 3 years
agobull 12 facultybull 35 bioinformatics bull 6 medical informatics staff
httpcancersangeracukcancergenomeprojectscensus
bull Chaired by Niki Sidiropoulosbull Participants from
ndash Pathologyndash Oncologyndash Radiation Oncologyndash Basic Scientists from UVM Cancer Center
bull Meet every other weekbull Discuss cases amp plan research
Genomic Oncology Trans Disciplinary Team
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Genomic Medicine Laboratory
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Genomic Medicine Program
Biobank
Genome Databank
Healthcare Databank
Genomic Education
Clinical Genomic Medicine
Genomic Translational
Research
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Assess the value of each genomic testAre we improving patient outcomesAre we improving cost effectiveness
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bull For each new genomic test collect datandash Genomic resultsndash Treatmentndash Responseoutcomesndash Total cost of care
bull Data combined from multiple data sources
Genomic Value Research Data Collection
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Genomic Value Research Partnerships
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Genomic Medicine Program
Genomic Translational
Research
Biobank
Genome Databank
Healthcare Databank
Clinical Genomic Medicine
Genomic Education
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Genomic Education
Undergraduate education
Medical student education
Resident amp Fellow Education
Healthcare provider education
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Molecular Pathology Rotation
UVM Honors CollegeControversies inModern Genomics
Integrate Genetics amp Genomic Medicine UVM COM Curriculum
bull Purpose Engagement to prepare for clinical genome sequencing
bull 73 UVM members had genome sequencedndash Pre- amp post-testing genetic counselingndash April 30 2016 Symposium where got access to
genome sequence on a web applicationbull Research in collaboration with Harvard
PeopleSeq Consortium (Robert C Green)
UVM Understand Your Genome Program
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bull Nine (123) with hereditary risk for clottingndash Six with Factor V Leiden Thrombophiliandash Three with Prothrombin-Related Thrombophilia
bull Six (82) with Familial Periodic Fever (TNFRSF1A)bull Six (82) with Mannose-Binding Protein Deficiency
ndash Two homozygous amp four compound heterozygous (MBL2)bull Four (54) with Hereditary Hemochromatosis (HFE)
ndash Two homozygous amp two compound heterozygousndash Penetrance very low
UVM UYG Common Genetic Conditions
bull Three (41) with pathogenic variantsndash One BRCA1 variant ndash One BRCA2 variant ndash One MYBPC3 variant -
UVM UYG The ldquoACMG 56rdquo
Breast Cancer
Hypertrophic Cardiomyopathy
bull 9 Alpha-1 Antitrypsin Deficiency (123)bull 7 Glycogen Storage Disease Type II (95)bull 6 Cystic Fibrosis (82)bull 1 Phenylalanine hydroxylase deficiency (PKU)bull 1 Congenital Disorder of Glycosylation Type IIbbull 1 Joubert syndrome
UVM UYG Carrier Status
UVM UYG PGx for 4 Most Common Drugs