Genomic Medicine Program An Overview Ronald Przygodzki, MD Assoc. Director, Genomic Medicine Acting Director, BLR

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Genomic Medicine ProgramAn OverviewRonald
Przygodzki, MDAssoc. Director, Genomic
MedicineActing Director, BLRD
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VA Genomic Medicine Program

• In 2006, the Department of Veterans Affairs
  launched the Genomic Medicine Program
• to examine the potential of emerging genomic
  technologies
• to optimize medical care for veterans
• to enhance the development of tests and
  treatments for relevant diseases

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Implementation

• As a first step, the Secretary established a
  distinguished 13-member Genomic Medicine Program
  Advisory Committee (GMPAC), a FACA committee, to
  lay the groundwork for the program
• Members include leaders in the fields of genetics
  research and medical genetics, genomic
  technology, health information technology,
  healthcare delivery, policy, program
  administration, legal counsel they come from the
  public and private sectors and academia
  representative of a VSO

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GMPAC Members

• Wayne Grody, MD, PhD (Chair), Professor
  Director of Molecular Pathology Laboratory, UCLA
• Michael S. Watson, PhD, FACMG, Exe. Director,
  American College of Medical Genetics
• Geoffrey S. Ginsburg, MD, PhD, Director, Center
  for Genomic Medicine, Duke University
• Muin J. Khoury, MD, PhD Director, NOPHG, CDC
• Daniel R. Masys, MD, Prof. Chair of Biomedical
  Informatics, Vanderbilt University
• Jonathan B. Perlin, MD, PhD, MSHA, FACP, CMO and
  Senior Vice-President, HCA Healthcare
• Margaret McGovern, MD, PhD, Prof. Human Genetics
  at Mount Sinai
• Peter G. Traber, MD, President CEO, Baylor
  College of Medicine
• Annette Taylor, MS, PhD, President, Director,
  Founder, Kimball Genetics
• Brion C. Smith, Col USA (Ret.) DDS, DOD Defense
  DNA Registry
• David S. Gorman, Exe. Director, Disabled Veterans
  of America
• Christine Q. Burtt, President CQB Associates,
  Denver, CO

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Veteran Consultation Project

• In 2007, VA launched a consultation project to
  assess veterans knowledge and attitudes about
  genomic medicine
• Interagency agreement with NHGRI and conducted
  under a cooperative agreement by the Genetics
  and Public Policy Center (GPPC) at Johns Hopkins
  University
• PI Kathy Hudson
• Focus Groups, Pilot, and Survey

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Assessing Veterans Attitudes About the Genomic
Medicine Program

• 10 focus groups in five locations of diverse
  participants during fall of 2007
• Solicit a wide range of perspectives
• Identify themes and issues
• Survey of 931 participants spring of 2008
• To test themes and messages from focus groups
• Paper describing findings in press in the journal
  Genetics in Medicine

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Survey Overview

• Fielded 4/24/08 5/5/08
• KN web-enabled panel
• Served in military, 4,193
• no longer active
• Responses 3,076
• Response rate 73
• Qualified (receive 931
• care through VA)
• Qualification rate 30

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Survey Overview

• Median time 20 minutes
• Description and schema of Genomic Medicine
  Program, to which participants could hyperlink
  back
• 80 items
• 67 items about the program, level of support,
  benefits and concerns, design aspects, and
  willingness to participate
• 13 items about military service, healthcare and
  use of VA services

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Survey Overview

• In analyses, data are weighted to the VA
  population demographics for
• Gender
• Race/Ethnic background
• Age
• Education
• Region

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Do you agree or disagree with the following
statement I am satisfied with the health care
that I receive through the VA.
Strongly Agree
Strongly Disagree
Disagree
Agree
Confidential. N931. Weighted. GPPC 2008
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(Immediately following description) Based on what
youve just learned, do you think the Genomic
Medicine Program should be done?
Now that youve had a chance to think more about
the Genomic Medicine Program, do you think it
should be done?
Confidential. N931. Weighted. GPPC 2008
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Based on what you know today, would you
participate in the Genomic Medicine Program if
you were asked?
Confidential. N931. Weighted. GPPC 2008
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Comparison of willingness to participate for
large genetic cohort studies by demographic
group VA vs. US
Confidential. N931. Weighted. GPPC 2008
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Demographics Associated with Willingness to
Participate

• Among African Americans (n93), the predictors of
  willingness to participate were strongly
  associated with
• Satisfaction with care at the VA
• Donating blood in the last 5 years

Confidential. N931. Weighted. GPPC 2008
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When thinking about participating in the program,
do you agree or disagree with the following
statements?
Disagree
Agree
Participating would make me feel like a guinea
pig
37
63
I would be concerned info could be used against
me
48
52
I would be concerned about govt having my samples
50
50
Participating would be easy
22
78
Participating would make me feel I was helping
veterans
83
17
I am curious about the influence of genes on
health
14
86
Confidential. N931. Weighted. GPPC 2008
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In deciding whether to participate or not, how
important would the following be to you?

• Receiving information about my health
• Knowing what kind of research being done using
  the database
• Knowing who to go to with a question or complaint
• Having my privacy protected
• Having a mechanism to change my mind and withdraw
  my sample and information at a later time
• Monetary compensation for my time

96 95 94 93 86 60
Confidential. N931. Weighted. GPPC 2008
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Keeping a Key

• Participants were given two ways data could be
  maintained - with a key linking name and number
  so that info could be updated and participants
  contacted or without a key so participants could
  not be identified or contacted or data updated
• 75 said a key should be kept

Confidential. N931. Weighted. GPPC 2008
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Assume research done in a certified lab. In
thinking about individual research results, which
would you prefer?
I would want to know all of my individual
research results
90
10
I would want to choose which individual research
results I would get back
69
31
I do not care if I get any individual research
results
83
17
I would not want any of my individual research
results
88
12
Confidential. N931. Weighted. GPPC 2008
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Privacy-related questions
Having my privacy protected is important to me
7
93
I would be concerned info could be used against
me
48
52
I would be concerned about govt having my info
and samples
50
50
Confidential. N931. Weighted. GPPC 2008
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Information from VA medical records that should
not be included

• Social security number 52
• Sexual behavior 17
• Sexual trauma 14
• Mental illness information 10
• Reproductive history 9
• Drug or alcohol abuse 8
• HIV infection or AIDS diagnosis 6
• Cancer diagnosis 5
• None of the above 40

Confidential. N931. Weighted. GPPC 2008
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In thinking about the consent you would give
would you prefer to give your permission
At the beginning, for all research projects
For select categories of research
For each research project
Confidential. N931. Weighted. GPPC 2008
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Do you think research should be allowed or
prohibited on
( allowed)
Cancer
Mental illness
PTSD
Alcoholism
Suscept. to env. exp.
Athletic ability
Stem cell research
Cloning
Confidential. N931. Weighted. GPPC 2008
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Do you think the following types of researchers
outside of the VA should be able to use the GMP
db and samples?
No
Yes
US academic or medical centers
80
20
Other health-related govt. agencies
30
70
US pharmaceutical companies
46
54
Academic or medical centers in other countries
57
43
Confidential. N931. Weighted. GPPC 2008
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If you were a participant, how important would
the following be to you?

• Serious consequences for researchers who violate
  my research agreement
• VA have safeguards to protect information from
  misuse and disclosure
• There would be a research agreement signed by
  researchers and participants
• It would be illegal for insurers and employers to
  get my information
• It would be illegal for law enforcement to get my
  information

98 98 97 95 87
Confidential. N931. Weighted. GPPC 2008
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Level of Participation

• 83 said program should be done
• 71 said they would participate
• 61 also said they would
• Attend a ½ day exam
• Allow medical records from non-VA health care to
  be added to the database
• Have follow up exams over time

Confidential. N931. Weighted. GPPC 2008
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Summary

• Participation associated with
• Attitudes about research
• Attitudes about helping and history of previous
  altruistic behaviors
• Curiosity about genetics
• Satisfaction with VA
• Demographic differences

Confidential. N931. Weighted. GPPC 2008
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• The fact that they have people sitting around
  talking about this in advance of even starting to
  build it tells me that theyre paying
  attentionThis right here is oversight, you know,
  at the get-go. So I think that thats a really
  good thing and I think ultimately its going to
  be one more way that veterans give something from
  themselves to make this country better.
• (Male, Mixed Group, DC)

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Infrastructure Development
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Infrastructure Development

• DNA Bank/Biorepository (Boston VA)
• About 30,000 blood samples collected as part of
  multi-site VA clinical trials (Cooperative
  Studies Program), with capacity for banking
  100,000 samples
• 6000 DNA samples
• RTS storage system and robotics
• DNA Coordinating Center at Palo Alto VA (link to
  clinical information and data analysis)
• Tissue repository (Tucson VA)
• Brain collection, tissue blocks

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Infrastructure Development (cont)

• Established Pharmacogenomics Analysis Laboratory
  in Little Rock, AR
• Clinical Laboratory Improvement Amendments (CLIA)
  certified research genomics laboratory
• Illumina platform
• Capillary-based analyses

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Infrastructure Development
Boston, MA
Philadelphia, PA
Palo Alto,CA
Little Rock,AK
Tucson, AZ
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Infrastructure Development (cont)

• VA central institutional review board (IRB)
• Reorganization of review for CSP DNA Bank
• Review of proposals for banking DNA as well as
  use of banked DNA will be managed centrally
• Genetics Subcommittee of Cooperative Studies
  Scientific Evaluation Committee (Genetics-CSSEC)
• Review new multi-site genetic epidemiology
  proposals as well as proposals for use of banked
  DNA

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Infrastructure Development (cont)

• Development of educational programs and tools for
  physicians and other health professional
• Collaboration between VA Employee Education
  Services and National Coalition for Health
  Professional Education in Genetics (NCHPEG)
• Web-based tool for heritable colorectal cancer
• Health-provider centric

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Computer Infrastructure Development

• GenISIS
• Genomic Information System for Integrative
  Science
• Louis Fiore, MD
• VINCI
• Veterans Informatics, Information Computing
  Infrastructure
• Jonathan Nebeker, MS MD

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GenISIS
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GenISIS
Current Research Paradigm
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Emerging Model
Current Model

• Comprehensive data collection and retention
• Data analyses
• Hypothesis generation (and validation)
• Interdisciplinary (Team science)
• Reuse of data

• Hypothesis testing
• Discipline-driven
• Targeted data collection
• Single use of owned data in silos

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Why GenISIS?

• Mission to enhance health care for veterans
  through personalized medicine
• Culture of research participation and
  affiliations
• Intramural funding with retained control of
  research artifacts
• A secure intranet and centralized administration
• Network of Medical Centers and CBOCs
• Robust national eHR and eCRF systems
• Data warehousing initiatives (VINCI)
• Longitudinal data availability
• Expanding biorepository capacity

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GenISIS Vision Statement

• Short Term (Research focused)
• To create and support a knowledge base that will
  facilitate independent research projects and
  allow for collaborative repurposing of data and
  results.
• Long Term (Patient care focused)
• Integration of clinical care and research
  activities for improved patient outcomes and
  research efficiencies

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GenISIS

• GWAS data expected from 50,000 subjects enrolled
  in VA CSP studies currently in planning or funded
• Schizophrenia
• Bipolar disease
• PTSD
• ALS (funded)

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GenISIS

• Securely gather, integrate, and analyze patient
  information
• Facilitate discovery research through shared
  expertise
• Repurpose data and results for secondary analyses
• Validate genomic medicine findings
• Integrate findings into clinical medicine

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GenISIS
Database, Query Interface, Analysis Environment,
Governance
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GenISIS

• In the absence of a new computational
  infrastructure and overarching policy from ORD,
  investigators generating these data are expecting
  to follow academic and industry models of data
  use.
• Leading to
• Silos of data storage and analysis on servers
  outside of the VA firewall
• Fewer scientific discoveries
• Lower return on research investment
• Loss of opportunity to develop VA expertise
• Loss of opportunity to integrate with VistA

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VINCI
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VINCI Mission Vision

• To serve the Consortium for Healthcare
  Informatics Research (CHIR) and eventually the
  greater VA research community by providing
  information technology and services that minimize
  the risk of veterans data loss and improve
  appropriate access to and use of veterans data.
• To become VA researchers preferred data source
  and data-processing environment within 4 years.

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VINCI Objectives

• Integrate existing data bases
• Integrate new data
• Extracted information
• Extracted meaning
• Provide a secure, high-performance computing
  environment
• Provide access to data
• Maintain customer support and outreach programs

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Overall Implementation Challenges

• Diverse technologies for molecular analysis
• Expression analysis, SNP, copy number analysis,
  mass spec, sequencing, transgenics, etc
• Technologies constantly evolving
• Information systems must be similarly protean
• Molecular data must be integrated with
  phenotypical data to achieve promise
• Data analysis and presentation needs vary by
  study
• As well as by researcher, bench scientist,
  bioinformatician, etc

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Ongoing Genomics/ Genetics-Related Projects

• VA funds 142 investigator-initiated Merit Review
  projects related to genetics/genomics
• wide spectrum of conditions prevalent in veterans
  such as schizophrenia, PTSD, bipolar disorder,
  Alzheimers, cardiovascular disease, diabetes,
  cancer (prostate, breast, colon, bladder, lung),
  substance abuse, stroke, chronic viral
  infections, autoimmune disorders, Gulf War
  Illness, etc.
• Genetic-association, pharmacogenomics
• Candidate gene analysis, SNP analysis, linkage
  studies, microarrays, siRNA, gene expression

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Interactions With Other Organizations

• The VA interacts, discusses and actively
  participates in
• Pharmacogenetic Research Network
• supported by several NIH Institutes
• National Human Genome Research Institute (NHGRI)
• The Institute of Medicine Roundtable on
  Translating Genomic-Based Research for Health
• The American Health Information Community (AHIC)
  and AHIC Successor (AHIC2)