Transcript USTAR Hiring Subcommittee Presentation April

The Problem: Today’s Medicine
The current system of health care delivery is inherently wasteful and
driven more by tradition than by scientific principle. A new paradigm
is needed to control costs and improve health (outcomes).
Most of today’s medications are less than 50% effective in the
intended population.
Adverse drug reactions caused by the failure to predict toxicity in
individuals and toxic drug-drug interactions now account for 100,000
patient deaths, 2 million hospitalizations, and $100 billion in health
care costs in the United States every year.
Current costs to bring a drug to market are astronomical (e.g. >$1B
and 10 or more years).
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The University of Utah
The Consequences of Reactive Health Care
Snyderman & Langheier, Genome Biology 2006; 7(2):104
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The University of Utah
The Consequences of Reactive Health Care
Snyderman & Langheier, Genome Biology 2006; 7(2):104
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The University of Utah
The Solution: Personalized Medicine
Multiple names/similar concepts: Common Goals:
Predictive Medicine
 Individualized Medicine
 Information-based Medicine
Increase the efficacy of treatment
 Minimize side effects
Improve cost-efficiency
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“The next ten years will be seen as a signal point
of transition in healthcare. Medicine will be transformed from an instinctive
art of alleviating symptoms to a science of personalized health care”.
Secretary of Health and Human Services, Michael Leavitt (2006)
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The University of Utah
Why a Genetic Approach is Warranted
# of Deaths*
Genetic
Susceptibility?
Heart Disease
696,947
Yes
Cancer
557,271
Yes
Stroke
162,672
Yes
Lower Respiratory Disease
124,816
Yes
Adverse Drug Reactions (est)
106,000
Yes
Diabetes
73,249
Yes
Disease
*National Vital Statistics Reports, Vol. 53, No. 17, March 7, 2005
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The University of Utah
Why Utah Provides a Unique Genetic Resource…
Large Families Plus
High Quality Clinical
Information are
Critical to Provide
Insight into the
Genetic Variations
that Cause Disease
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The University of Utah
Utah Population Database (UPDB)
University of Utah research
resource
Over 30 years of research
About 9.0 million documents
65 approved projects
http://www.hci.utah.edu/groups/ppr/
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The University of Utah
UPDB Resource
Conduct studies that require individual and familial data
Family histories (mainly Utah and SE Idaho families)
 Genealogies: Family History Library, maintained by LDS Church
 Family reconstitution: Create families from Utah’s vital records
◦ Create maternal and paternal birth histories
 Link across generations - 11 generations for some families
Medical information is linked to family histories
 State wide cancer records
 Vital records: cause of death and medical details from birth certificates
 University of Utah Health Sciences medical records
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The University of Utah
Sources for Data
Church of Jesus Christ
of Latter-day Saints
(LDS genealogies)
Utah SEER
Intermountain
Cancer Registry
Healthcare
UPDB
Resource for Genetic
& Epidemiologic
Research
Utah
Department of Health
Social Security
Death Index
Cancer Data
Registry of Idaho
University of Utah
Hospitals and Clinics
Utah
Department of Public Safety
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The University of Utah
Documents Available in UPDB
Genealogy (over 170,000 family group sheets)
Utah birth certificates (1915-21, 1947-2005)
Utah marriage and divorce (1978-2004)
783,993
Utah death certificates (1904-2005)
Social security death index
Utah Cancer Registry (in situ and invasive)
Cancer Data Registry of Idaho
124,079
Driver License
Total
1,599,292
2,088,389
707,971
479,311
216,266
2,773,562
8.9 million
Linked into 6.5 million “person records” and across generations
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The University of Utah
Utah Family, Circa 1900
10
8
4
7
2
F
3
M
12
1
5
Father (F), Mother (M) and children by birth order
Married 1853, 12 Children, 3 Infant deaths (#6, 9, 11)
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The University of Utah
Utah Family in UPDB
1807
1802
1807
1802
1889
1870
1889
1870
Canada
New York
Canada
New York
Maternal side
8th of 15 children
8th of 15 children
1
1
1854
1854
1932
1932
2
2
1855
1855
1940
1940
3
3
1857
1857
1930
1930
4
4
1859
1859
1931
1931
5
5
1861
1861
1892
1892
1817
1819
1817
18191850
1854
1854
England 1850
Connecticut
England Connecticut
1st of 5 children
F1st of 5 children
M
M
1837
1837
1917
1917
6
6
1863
1863
1863
1863
Paternal side
F 1835
1835
1915
1915
7
7
1864
1864
1939
1939
8
8
1867
1867
1952
1952
9
9
1869
1869
1869
1869
10
10
1870
1870
1902
1902
11
11
1872
1872
1872
1872
12
12
1874
1874
1943
1943
Spans 11 generations from 1807 to 2005
Couple (in picture): 4,289 descendants (3,821 living)
Paternal side: 6,510 descendants (5,714 living)
Maternal side: 19,350 descendants (16,973 living)
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The University of Utah
Utah: Extraordinary Research
Opportunity
Low inbreeding rate
 Large initial founding population
 High rates of immigration from diverse outside populations
Extrapolate findings to broad spectrum of US and Western and Northern
European populations
Identify predisposition to disease
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APC gene mutation in colon cancer
BRCA1 and BRCA2 breast cancer mutations
P16 gene mutation in melanoma cancer
Prostate cancer susceptibility gene
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The University of Utah
Inherited Disorder
Gene
Colon Cancer (Familial Adenomatous Polyposis Coli)
APC
Neurofibromatosis
NF-1
Breast Cancer
BRCA-1
BRCA-2
Melanoma
p16
Cardiac arrhythmias (Long QT Syndrome)
KVLQT1
minK
HERG
MiRP1
Supravalvular Aortic Stenosis
ELN
Alport Syndrome
COL45A5
Hypertension
XIB
AGT
Macular degeneration (Stargardt’s Disease)
ABCR
Ulnar-Mammary Syndrome
TBX3
Williams Syndrome
LIMK1
Porphyria Cutanea Tarda
URO-D
Inflammatory Syndromes
PAF-AH
Chediak-Higashi Syndrome
CHS-1
Neonatal Epilepsy
KCNQ2
Genetic Disorders in
Which the
Molecular Basis
Was Discovered at the
University of Utah
KCNQ3
Hyperkalemic Periodic Paralysis
SCN4A
Paramyotonia Congenita
SCN4A
Potassium Aggravated Myotonia
SCN4A
Hypokalemic Periodic Paralysis
CACNA1S
Periodic Paralysis 3
KCNE3
Andersen’s Syndrome
KCNJ2
Frings Audiogenic Epilepsy
Mass1
Spinocerebellar Ataxia Type 7
SCA7
Familial Advanced Sleep Phase Syndrome
hPer2
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The University of Utah
Sources of Medical Information
Research Infrastructure - Master Subject Index
U of U Health Sciences Center (UUHSC), Enterprise data warehouse
(EDW)
 Matched over 1.0 million (70%) patient demographic records
 About 18 new projects
Huntsman-Intermountain Cancer Care Program,
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Link to Enterprise data warehouse
Developing an agreement to link data sets
5.3 million individuals in Enterprise Data Warehouse
Proposed to begin summer 2007
A use agreement has not be developed
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The University of Utah
New Research Opportunities
Access to University of Utah Medical Records
 Matched 1.0 million patient demographic records
16 new research projects, e.g.
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Cardiovascular mortality in renal transplant patients
Fibromyalgia and chronic fatigue syndrome
Hereditary angioneurotic edema
Inflammatory bowel disease
Macular degeneration and other eye diseases
Polycystic ovary syndrome
Psoriasis
Rheumatoid arthritis
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The University of Utah
Examples of Types of Studies
 Cancer Studies
◦
Cancer genetics: breast, colon, melanoma, pancreas, prostate
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Familial aggregation of cancers
 Obstetric complications and childhood studies
◦
Preeclampsia and preterm births
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Birth defects, autism, juvenile idiopathic arthritis, developmental hip dysplasia
 Chronic and other diseases and conditions
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Diabetes, psoriasis, rheumatoid arthritis, inflammatory bowel disease
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Macular degeneration, giant cell artiritis, interstitial lung disease, mullerian anomalies,
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Chronic pain, aneurysms, asthma, pelvic organ prolapse
 Aging and mortality
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Longevity
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Memory in aging and Alzheimer’s Disease
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The University of Utah
Security and Confidentiality
Not a public database – for research only
 Researchers have no electronic access to identifying information
State of the art database
Policies and procedures on confidentiality
 All projects are reviewed by IRB and data contributions
Require researchers to sign confidentiality agreements
Contact of potential subjects by an appropriate third party
Wylie and Mineau, Biomedical databases: protecting privacy and promoting research. Trends in
Biotechnology, March, 2003.
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The University of Utah
Unparalleled Discovery Assets
Quebec (Galileo)
Iceland (deCODE)
Estonia (EGeen)
Utah (USTAR PM)
UK (UK BioBank)
Wisconsin (Marshfield)
Key advantages of Utah PM Assets
 Most extensive genetic records
 Extensively integrated medical records
 Largest research institution
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The University of Utah
Personalized Medicine Initiative
The goal of this proposed initiative is to develop a
broad-based program that builds on Utah’s core
strengths in human biology and genetics, and aims
to further the molecular understanding of disease
mechanisms to discover and direct diagnostic
measures and therapeutic approaches to the right
population of people, at the right time -ideally while
they are still well.
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The University of Utah
Utah’s Natural Resource for
Personalized Medicine
Utah Population Database (UPDB)
 Tens of millions of records covering more
than 7 million persons;
 Dynamic integration of genealogic,
demographic, and medical records
Utah Genetic Reference Project
 Access to genetic and phenotypic data on
the genetic reference families used for the
Human Genome Map and HapMap projects
UUHSC Medical Records
 1.5 million person records have been
Linked into core UPDB;
 ICD9 Codes, pharmacy data, lab results
Research Programs
Utah
Genetic
Reference
Project
(UGRP)
Clinical Trials Infrastructure
 Thought leaders participating in the
development of new targeted therapies and
molecular diagnostics
Utah
Population
Database
(UPDB)
University
Hospital
Medical
Records
(UUHSC)
Clinical Trials
Infrastructure
Research Programs
 Access to critical longitudinal data/samples
 Robust prospective recruitment process
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The University of Utah