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Introduction to the Medical CommunityIntroduction to the Medical Community
The Measurement to Understand Reclassification of Disease Of Cabarrus/Kannapolis Study
The The M.U.R.D.O.C.K. M.U.R.D.O.C.K. StudyStudy22 Oct 200722 Oct 2007
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AgendaAgenda
Welcome and introductory commentsWelcome and introductory commentsAndrew Conrad PhD - CSO LabCorp and NCRCAndrew Conrad PhD - CSO LabCorp and NCRC
Lynne Scott Safrit - President Castle & CookeLynne Scott Safrit - President Castle & Cooke
Allan Dobson MD – VP Clinical Practice Development, CFMAllan Dobson MD – VP Clinical Practice Development, CFM
Overview of study plan - Rob Califf MDOverview of study plan - Rob Califf MD
Overview of -omics study tools – Jessie Tenenbaum PhDOverview of -omics study tools – Jessie Tenenbaum PhD
Example of liver project - John McHutchison MDExample of liver project - John McHutchison MD
Community engagement plan - Lloyd Michener MDCommunity engagement plan - Lloyd Michener MD
Discussion - AllDiscussion - All
Timeline and next steps - Victoria Christian Timeline and next steps - Victoria Christian
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NCRC collectively improving human healthNCRC collectively improving human health
Farming Practices
Food Sciences
Nutrition
Effective Healthcare
Disease Management
Health Maintenance
Medical Education
Public Health
Population Health
Productivity
Global Health
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In 20 years…In 20 years…
All people in developed nations will have —All people in developed nations will have —
An electronic health recordAn electronic health record
Biological samplesBiological samples
Digitized imagesDigitized images
Healthcare will be personalized using an individual’s Healthcare will be personalized using an individual’s images, samples and clinical data.images, samples and clinical data.
The health of a community will be monitored using The health of a community will be monitored using aggregate records.aggregate records.
Kannapolis — as hub of the Carolinas — could define Kannapolis — as hub of the Carolinas — could define this future through a public-private partnership.this future through a public-private partnership.
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Build value using assets already Build value using assets already in our reach.in our reach.
Sub-classify major diseases into Sub-classify major diseases into populations with specific risks populations with specific risks and optimal therapy.and optimal therapy.
Apply new knowledge to the Apply new knowledge to the study of community health.study of community health.
Re-define clinical research using Re-define clinical research using the power of genomics and the power of genomics and biomedical informatics.biomedical informatics.
Re-write the textbook of medicine.Re-write the textbook of medicine.
The MURDOCK Study will …The MURDOCK Study will …
ImproveImprovehumanhumanhealth.health.
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The MURDOCK Study will ...The MURDOCK Study will ... Fuel the financial success of the DHMRI Core Fuel the financial success of the DHMRI Core
Laboratory and Biorepository.Laboratory and Biorepository.
Foster breakthrough collaborations between NCRC Foster breakthrough collaborations between NCRC schools with diverse and interconnected schools with diverse and interconnected perspectives and expertiseperspectives and expertise
Quickly increase the visibility and scientific impact Quickly increase the visibility and scientific impact of the DHMRI Lab.of the DHMRI Lab.
Attract the scientific community.Attract the scientific community.
Attract the biotechnology community.Attract the biotechnology community.
Engage the local population in a high-impact, Engage the local population in a high-impact, internationally recognized project.internationally recognized project.
The modern equivalent of the Framingham Heart StudyThe modern equivalent of the Framingham Heart Study
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Current data assets & DHMRI tools:Current data assets & DHMRI tools:Powerful once-in-a-lifetime value proposition Powerful once-in-a-lifetime value proposition
Liver Disease
ObesityDiabetes
Massive patient database
to be mined
Heart Disease
Brain Disorders
Mental Illness Alzheimers
CancerBreast
ProstateLung
Genomics, Proteomics, MetabolomicsDHMRI Core Lab
Image AnalysisDHMRI Core Lab
AgingArthritis
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A new era of biomedical researchA new era of biomedical research
Novel research technologies have enabled the Novel research technologies have enabled the study of thousands of molecules at a timestudy of thousands of molecules at a time
Referred to as “high throughput” approachReferred to as “high throughput” approach
These novel methods enable ‘-Omics’ scale These novel methods enable ‘-Omics’ scale researchresearch
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What is ‘-Omics’?What is ‘-Omics’?
The study of the The study of the totalitytotality of a type of biological of a type of biological datadata
All genes: GenomicsAll genes: Genomics
All transcribed genes: TranscriptomicsAll transcribed genes: Transcriptomics
All proteins: ProteomicsAll proteins: Proteomics
All metabolites: MetabolomicsAll metabolites: Metabolomics
Omics scale research has enabled patient Omics scale research has enabled patient profiling at the molecular levelprofiling at the molecular level
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Continuum of -OmicsContinuum of -Omics
Genes Genes mRNA mRNA Proteins Proteins Metabolites Metabolites
GenomicsGenomics
TranscriptomicsTranscriptomics
ProteomicsProteomicsMetabolomicsMetabolomics
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Genomics and the mediaGenomics and the media
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Glass slide
An example: DNA MicroarraysAn example: DNA Microarrays
Isolate mRNA, label
Dr. Russ Altman, Stanford Univ.
Cells of interest
Reference sample
Known DNA
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DNA Microarray visualization: heatmapsDNA Microarray visualization: heatmaps
Experiment 1
(e.g. Patient X)
2 3 4 5 6Gene 1
Gene 2
Expt 1
Gene 5Gene 6Gene 7Gene 8
Gene 3Gene 4
Gene 9
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An opportunity An opportunity
For the first time, diseases can be defined by molecular fingerprints or profiles
Mechanistic pathways of diseases can be elucidated
Symptomatic descriptors can be replaced by meaningful tools for stratification
These tools will enable truly personalized medicine
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Medicine todayMedicine today
Drugs are developed to treat all patients with the same clinical diagnosis - “one size fits all”
Many drugs only work in less than half of the patients for which they are prescribed
Over 100,000 people die annually from drug related adverse events - a ‘top 10’ cause of death
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‘‘-Omics’ technologies can help predict -Omics’ technologies can help predict treatment response.treatment response.
ResponderResponder Adverse eventAdverse event Non-responderNon-responder
CancerCancer
Excercise + Excercise + Diet ADiet A
Exercise +Exercise +Diet BDiet B
Exercise +Exercise +Diet +Diet +
MedicationMedication
DiabetesDiabetes -Omics Technologies-Omics Technologies
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Combining clinical and molecular data Combining clinical and molecular data will redefine disease management.will redefine disease management.
Quantify risks of developing diseases.Quantify risks of developing diseases. Apply preventive measures more effectively. Apply preventive measures more effectively.
Establish diagnosis earlier. Establish diagnosis earlier. Prevent disability by treating earlier. Prevent disability by treating earlier.
Predict death and disability. Predict death and disability. Use healthcare resources strategically. Use healthcare resources strategically.
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Three horizons of MURDOCK StudyThree horizons of MURDOCK Study
Horizon 1
•Use assets on hand to generate molecular data
•Generate hypotheses by leveraging bioinformatics
Horizon 1.5•Engage community
•Build community registry
Horizon 2
•Validate hypotheses prospectively
•Apply new knowledge to local community through partnership with local medical community
•Improve human health
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Outcomes of Hepatitis C virus infectionOutcomes of Hepatitis C virus infection
Spontaneous clearance (~25%)
Chronic infection
Treatment
Responders Non-responders (>50%)
Hepatic Fibrosis Steatosis Insulin resistance Dyslipidemia
Increased risk of diabetes
Unknown consequences
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Reclassification of HCV diseaseReclassification of HCV disease
Use genomic technologies to subset patients Use genomic technologies to subset patients based on their molecular signaturebased on their molecular signature
This signature may become a useful marker of: This signature may become a useful marker of:
Treatment response – therapeutic decision-makingTreatment response – therapeutic decision-making
Development of fibrosis or steatosis - non-invasive Development of fibrosis or steatosis - non-invasive diagnostic alternativediagnostic alternative
Insulin resistance or dyslipidemia – may have Insulin resistance or dyslipidemia – may have broader relevance for diagnosing and treating non-broader relevance for diagnosing and treating non-HCV patients with these conditionsHCV patients with these conditions
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Selection of biomarkers for HCV profilingSelection of biomarkers for HCV profiling
Standard available assays: inflammatory, lipid Standard available assays: inflammatory, lipid metabolism, glucose metabolism, etc.metabolism, glucose metabolism, etc.
Novel protein Novel protein biomarkers – biomarkers – proteomic discoveryproteomic discovery
Novel protein Novel protein biomarkers – biomarkers – genetic approachesgenetic approaches
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Novel biomarker discovery strategiesNovel biomarker discovery strategies
Proteomic discoveryProteomic discovery Genetic discoveryGenetic discovery
gt1gt1 gt2gt2 gt3gt3
RR
NRNR
Open discovery platform allows for discovery of novel protein biomarkers (host or viral-specific) that may be associated with treatment response and/or HCV genotype
These biomarkers, along with others, will be typed in a large HCV patient cohort
Unbiased discovery platform tests for association of >500,000 gene variants with HCV outcomes and/or quantitative traits (protein markers)
Genes discovered in this way may become useful protein biomarkers or remain as DNA diagnostics
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Molecular profiling of HCV patientsMolecular profiling of HCV patients
Type large number of Type large number of biomarkers in ~1000 biomarkers in ~1000 chronic HCV patients chronic HCV patients from the Duke from the Duke Hepatology Research Hepatology Research Clinic cohortClinic cohort
Tx responseFibrosisSteatosisDiabetesDyslipidemia
Use statistical Use statistical modeling to subset modeling to subset HCV patients based HCV patients based on common on common biomarker signaturesbiomarker signatures
Correlate molecular Correlate molecular signatures with signatures with outcomes in HCV outcomes in HCV patients and similar patients and similar traits in non-HCV traits in non-HCV patientspatients
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Deploy assets for maximum potential Deploy assets for maximum potential benefit to communities.benefit to communities.
Uncover new knowledge in diseases that afflict large Uncover new knowledge in diseases that afflict large patient populations.patient populations.
Epidemics — obesity, diabetes, depressionEpidemics — obesity, diabetes, depressionDiseases of aging — arthritis, dementiaDiseases of aging — arthritis, dementia
Use this new knowledge in clinical practice.Use this new knowledge in clinical practice.
Make decisions based on breakthroughs in the Make decisions based on breakthroughs in the individualized treatment of breast cancer and depressionindividualized treatment of breast cancer and depression
Make new discoveries with commercial potential.Make new discoveries with commercial potential.
Contributory drug-able pathwaysContributory drug-able pathwaysNovel biomarkersNovel biomarkers
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Challenge of biomedical informatics:Challenge of biomedical informatics:Turning data into knowledgeTurning data into knowledge
DATA
Knowledge
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Groundwork for successful community Groundwork for successful community engagementengagement
Transparency of effortsTransparency of efforts
Advice from appropriate community groupsAdvice from appropriate community groups
Questions to ask: how are citizens best reached? where Questions to ask: how are citizens best reached? where do they gather? how do they prefer to receive do they gather? how do they prefer to receive information?information?
Preparation of documents and study plans in Preparation of documents and study plans in iterative process with feedback from communityiterative process with feedback from community
Communication strategy based on community Communication strategy based on community groups’ advicegroups’ advice
Formation of Community Advisory GroupFormation of Community Advisory Group
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Possible modes of engagementPossible modes of engagement Interactive websiteInteractive website
Community surveysCommunity surveys
Posters, brochures, other written materialsPosters, brochures, other written materials
Educational presence at community events (e.g., health fairs)Educational presence at community events (e.g., health fairs)
Targeted cable television programsTargeted cable television programs
Local physician and patient with 15 min on specific topic (living with Local physician and patient with 15 min on specific topic (living with osteoarthritis, managing diabetes, etc.)osteoarthritis, managing diabetes, etc.)
Videos for doctors’ officesVideos for doctors’ offices
Interactive kiosksInteractive kiosks
Open communication with local media outletsOpen communication with local media outlets
Meetings with community groups (health related and non-health Meetings with community groups (health related and non-health related)related)
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Community Registry Community Registry Accelerating Discovery:Accelerating Discovery:
Suppose we identify a Biomarker that Suppose we identify a Biomarker that distinguishes a sub-population of patients distinguishes a sub-population of patients correlating with new insulin resistancecorrelating with new insulin resistance
If this is true, we’d treat differently to If this is true, we’d treat differently to achieve better patient outcomesachieve better patient outcomes
We need to We need to testtest this to assure improved this to assure improved patient outcomespatient outcomes
Positive result would drive creation of the Positive result would drive creation of the diagnostic and care guidelines.diagnostic and care guidelines.
FindingFinding
ApplicationApplication
Translation Translation into Practiceinto Practice
ConfirmConfirm
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Community RegistryCommunity Registry
Allow patients to declare interest in research Allow patients to declare interest in research participationparticipation
Store informationStore information
People interested in research participationPeople interested in research participation
Summary level health informationSummary level health information
Permission to contact Permission to contact
Primary physicianPrimary physician
Accelerate discovery by having this information Accelerate discovery by having this information when discoveries are ready to be testedwhen discoveries are ready to be tested
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SummarySummary
We are committed to building transparent, open We are committed to building transparent, open partnership with local community.partnership with local community.
We will seek to maximize opportunities to have We will seek to maximize opportunities to have meaningful impact on local human health and meaningful impact on local human health and local economy.local economy.
The MURDOCK Study offers an opportunity for The MURDOCK Study offers an opportunity for the local community to have global impact by the local community to have global impact by generating knowledge that improves health and generating knowledge that improves health and alleviates disease.alleviates disease.
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