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Genomic Medicine Program
September 27, 2007
2
Background
Department of Veterans Affairs (VA) launched Genomic Medicine Program In 2006
Goal to explore potential to optimize medical care and enhance development of tests and treatments
VA uniquely positioned for genomic research due to electronic medical record system for over 5.3 million veterans
3
Background (cont’d)
Veteran volunteers will provide blood sample for genetic analysis.
Genetic information linked to their electronic health records
Goal to discover new genetic associations, genetic bases for differential responses to drugs, and adverse drug reactions.
4
Veteran Consultation Project
VA Secretary established Genomic Medicine Program Advisory Committee (GMPAC)
GMPAC felt earning trust of and partnering with veterans was paramount
Recommended VA assess veterans’ knowledge, attitudes, and beliefs about genomic medicine and research participation
5
Veteran Consultation Project (cont’d)
VA moved to assess veterans’ knowledge and attitudes in 2007.
VA Established inter-agency agreement (IAA) with National Human Genome Research Institute (NHGRI) to add veteran-specific component to their ongoing project to assess public attitudes toward genomic medicine.
6
Veteran Consultation Project (cont’d)
NHGRI project conducted by Genetics and Public Policy Center (GPPC) at Johns Hopkins University (PI: Kathy Hudson)
GPPC will conduct veteran focus groups and surveys over a 1-year period ending summer 2008
7
Scope of Genomic Medicine Focus Groups/ Surveys
Knowledge and attitudes General acceptability of proposed goals and
methods of VA genomic studies Areas of concern Consent issues Methods of recruitment Role of Veteran Service Organizations (VSOs) Expectations of potential participants re
confidentiality, privacy, and security Use of research findings Return of results, ongoing communication, etc.
8
Focus Groups
Nine focus groups planned Focus Group guides and questions
developed in consultation with VACO Veterans recruited from:
– Local chapters of VSOs reflecting diversity of veterans using VA healthcare system
– VAMCs, VA Community-Based Outpatient Clinics, and VET Centers (Readjustment Counseling Centers) from various geographic regions and demographic groups
9
Focus Groups (cont’d)
Locations/ time line for the focus groups:
LOCATION DATES
Washington DC (Pilot) September 19
Atlanta September 26-27
The Bronx October 4
Denver October 17-18
San Diego October 23-24
10
Focus Groups (cont’d)
Two focus groups at each site, except Atlanta, where women will be added.
About 10-12 participants in each group Focus Group Guide pilot-tested with VSO
leaders/members Washington, DC
11
Survey
Based on issues raised in focus groups, GPPC will develop internet-based survey
Plan to survey 850 veterans, including those receiving their healthcare through both VA and elsewhere
12
GMPAC Working Groups
Ethics Advisory - ethical considerations, esp. informed consent of special populations
Hereditary Non-Polyposis Colon Cancer (HNPCC) - research on routine genetic/genomic analysis for clinical management of HNPCC & sporadic colon cancer
Endocrine Tumors - research on routine genetic/genomic analysis for clinical management of tumors with known genetic abnormalities
13
Resource Development
DNA banking: 11 multi-site Cooperative Studies Program (CSP) clinical trials, 1 CSP Registry (ALS), 1 non-CSP study (VA Aging Cohort Study)
DNA Bank locations: Boston MAVERIC and Palo Alto (DNA Coordinating Center for CSP)
Shadow DNA bank: Planned back-up for samples and enhancement of capacity – location TBD in FY2008
VA central institutional review board (IRB): In development
14
Resource Development (cont’d)
Clinical Laboratory Improvement Amendments (CLIA)-certified research genomics laboratory RFA in 2006– Pharmacogenomics Analysis Laboratory (PAL)
established in Little Rock, AR; Dr. Steven Shichman as Director. Other PALs in development.
Plan for Centers for Genetic Epidemiology to enhance statistical & other support for large-scale genetic epidemiology studies (FY 2008)
Genetic Epidemiology Review Committee for reviewing genetic epidemiology studies as well as DNA banking protocols for CSP sub-studies
15
Ongoing Genomics/ Genetics-Related Projects
VA funds 142 investigator-initiated Merit Review projects
Cover wide spectrum of conditions prevalent in veterans: schizophrenia, PTSD, bipolar disorder, substance abuse, Alzheimer’s, cardiovascular disease, diabetes, cancer (prostate, breast, colon, bladder, lung), stroke, chronic viral infections, autoimmune disorders, Gulf War Illness, etc.
Genetic-association, pharmacogenomics Candidate gene analysis, SNP analysis, linkage
studies, microarrays, si RNA, gene expression
16
Personalized Medicine RFA in 2006
To validate clinical strategies for prospective use of genetic information in pharmacotherapeutics
Five applications reviewed in April 2007, resulting in funding: “Bayesian Adaptive Methods with Pharmacogenomics to Treat Bladder Cancer”
RFA extended to December, 2008
17
Genetics of Functional Disability in Schizophrenia and Bipolar Disorder
Serious Mental Illness (SMI) Cohort Study concept letter approved for planning/submitting full proposal to CSP.
Goal to develop 3 longitudinal cohorts, each consisting of 5000 veterans suffering from 1) schizophrenia or 2) bipolar disorder or a 3) control group
Plan to obtain genetic material for genome scanning, identify genetic variants that contribute to functional disability, and assess genetic determinants of responsiveness to therapeutic agents as well as genetic contributions to toxic side effects.
18
PTSD Genetics
PTSD Genetics Working/Planning Group in development; 1st meeting September 25, 2007
Goal to explore/ define basis to conduct research on PTSD through development of new/ expansion of current cohorts (e.g., ongoing CSP clinical trials).
Via careful clinical characterization and genetic analyses, cohort should be longitudinally available
Use cohort to determine genetic variants contributing to PTSD risk, as well as treatment response and outcomes.
19
Interactions With Other Organizations
VA involved in ongoing discussions and in working groups with: – Pharmacogenetic Research Network, supported by
several NIH Institutes– National Human Genome Research Institute
(NHGRI)– Institute of Medicine Roundtable on Translating
Genomic-Based Research for Health– American Health Information Community (AHIC)
20
Data and Sample Sharing Policy
Samples and data will only be available to VA researchers.
Policy may change to reflect Veterans’ attitudes revealed in Veteran Consultation Project focus groups and survey.
21
Fears about Genetic Research
Genetic information could be used against people by employers or insurers– To counteract concern, House passed the
Genetic Information Nondiscrimination Act (2007), which is expected to be passed in Senate and signed into law soon.
22
Fears about Genetic Research (cont’d)
Veteran’s benefits would be affected if shown to have genetic disposition to a disease– Having dealt with genetically based diseases,
consistent position of VA that genetic disease that first appears during a period of active service constitutes a service-connected condition
– Genomic medicine program aims only to improve effectiveness of VA’s health care system
VA Tissue Banking Policies
September 2007
24
Policy Topics Covered
1. Definitions of human biological specimens, banked specimens, and de-identified
2. On-site tissue banks
3. Off-site tissue banks
4. Storage at non-academic, for-profit institutions
5. Requirements for applying for off-site waiver
6. Elements required in informed consent
25
Human Biological Specimen Definition
Any material derived from human subject, such as blood, urine, tissues, organs, hair, nail clippings, or any other cells or fluids
Could be collected for research purposes or as residual specimens from diagnostic, therapeutic, or surgical procedures.
26
Banked Specimens
Biological specimens collected and stored for future research purposes
– Beyond scope of work described in original protocol and informed consent
– Or collected under protocol designed for banking of specimens
27
Non-Banked Human Biological Specimens
Used only for specific purposes defined in protocol
Also, destroyed either when specific testing/use is completed or at end of protocol.
Must obtain waiver from ORD if:– Protocol >/= 5 years and specimens stored off-site at
non-profit institution until end of protocol– Specimens stored off-site at non-academic, for-profit
institution for >3 months
28
Non-Banked Specimens
If specimens sent to non-VA institution for testing (as defined in protocol), remainder of specimens must be destroyed or returned to VA for destruction once specific analyses are performed
If specimens destroyed at another institution, that institution must certify destruction in writing.
29
De-identified Data Health or other information about individual
that: – Does not contain any of 18 HIPAA identifiers
AND
– Is de-identified according to Common Rule
NOTE: Coded information is not considered de-identified if tissue bank or data coordinating center has access to codes
30
18 HIPAA Identifiers
1. Names or initials
2. All geographic subdivisions smaller than state
3. All elements of dates except year; all ages > 89
4. Telephone numbers
5. Fax numbers
6. E-mail addresses
7. Social Security numbers (or scrambled SSNs)
8. Medical record numbers
9. Health plan beneficiary numbers
31
18 HIPAA Identifiers (cont’d)
10. Account numbers
11. Certificate or license numbers
12. Vehicle identifiers
13. Device identifiers and serial numbers
14. URLs
15. IP addresses
16. Biometric identifiers, including finger and voice prints
17. Full-face photographs and any comparable images
18. Any other unique identifying number, characteristic, or code
32
On-Site Tissue Banks
ORD approval not required if bank is located at VA site by VA-paid investigator
ACOS/R or research office should maintain records of all tissue banks within facility
33
On-Site Tissue Banks (cont’d)
If VA site lacks resources for bank, may store at any VA on-site bank
Also use on-site storage at Massachusetts
Veterans Epidemiology Research and Information Center (MAVERIC) core laboratory at Boston VA (serves as Cooperative Studies Program (CSP) Genetic Tissue Core Laboratory)
34
Off-Site Tissue Banks
Must obtain waiver from ORD before banking off-site
Approved on per protocol basis
Exception: National Cancer Institute (NCI)-sponsored cooperative banks designated as VA-approved – If used for NCI protocols (e.g., SWOG-
supported tissue bank can be used for SWOG protocols without ORD approval).
35
VA-Approved NCI Tissue Banks
Clinical Trials Cooperative Groups Tissue Resources: – American College of Surgeons Oncology Group (ACOSOG) – Cancer and Leukemia Group B (CALGB) – Eastern Cooperative Oncology Group (ECOG) – Gynecologic Oncology Group (GOG) – North Central Cancer Treatment Group (NCCTG) – National Surgical Adjuvant Breast and Bowel Project (NSABP) – Radiation Therapy Oncology Group (RTOG) – Southwest Oncology Group (SWOG)
Cooperative Breast Cancer Tissue Resource Cooperative Human Tissue Network Gynecologic Oncology Group Tissue Network Cancer Prevention Network
36
Specimen Banking Requirements Summarized
Banking not permitted at non-academic, for-profit institution
Must be labeled with code that does not contain any of 18 HIPAA identifiers
Key to code must be maintained at VA (unless compelling reason otherwise)
37
Requirements for Data Related to Banked Specimens
Summarized If data linked to sample leaves VA, it must
be de-identified or stored in encrypted database according to FIPS 140-2 standards
See VA Directive 6504 “Restrictions on Transmission, Transportation and Use of, and Access to, VA Data Outside VA Facilities”
38
Requirements Summarized for Non-Banked Specimens Stored at
Non-Academic For-Profit Sites
If specimens held >90 days, waiver must be obtained from ORD
Only analyses/tests listed in protocol and informed consent may be performed
Code must be maintained at VAMC All specimens and associated data must be de-
identified DNA and RNA may not be analyzed Company must inform PI in writing when
samples are destroyed.
39
Requirements Summarized for Non-Banked Specimens Stored at
Non-Academic For-Profit Sites (cont’d)
HIPAA authorization must expire Case reports may not contain initials if leave VA Specimens must be destroyed upon request of
subject Before company personnel may view files at VA,
must complete VA security and privacy training Specimens must be destroyed < 1 year of study
completion date
40
Application Process Requirements
Must complete VA form 10-0436 (fillable pdf form, save using Acrobat Reader v 7 or higher (http://www.va.gov/vaforms/medical/pdf/vha-10-0436-fill.pdf)
Information requested on p. 5 of application can be scanned and attached to pdf or e-mail:– Biographical sketch of PI– Research protocol– Tissue bank manual or SOPs– VA consent form
41
Application Process Submission
Application should be e-mailed to Marilyn Mason ([email protected]); also carbon copy ACOS/R
Alternatively, form and requested information can be mailed to address provided on form
42
Application Process Review
ORD usually takes 2 weeks to process application
After application is reviewed, PI and ACOS/R will receive memo listing any issues needing resolution (such as informed consent)
43
Applications for Multi-Site Trials
If several VAMCs plan to participate in same clinical trial, only one needs to apply for waiver
See list of multi-site clinical trials on VA R&D web site.
44
Informed Consent
If protocol involves banking, elements required in informed consent to ensure transparency to Subject
Elements posted on VA R&D web site:– Types of samples/ length of time stored– Name and location of tissue bank– Types of future studies– Subject may withdraw from study and request
samples be destroyed– If specimen shared with other researchers
45
Informed Consent (cont’d)
No need to narrowly specify future uses of banked specimens
If not specific, PI should explain what phrases such as “related diseases” or “unspecified research” mean for use of sample and impact on subject
46
Contact Information
For additional information, contact Marilyn Mason
– E-mail: [email protected]
– Phone: 202/ 254-0496
– Fax: 202/ 254-0521