Genomic Medicine Program September 27, 2007

1. Genomic Medicine ProgramSeptember 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:

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 inFY2008 • 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

23. VA Tissue Banking Policies September 2007

24. Policy Topics Covered • Definitions of human biological specimens, banked specimens, and de-identified • On-site tissue banks • Off-site tissue banks • Storage at non-academic, for-profit institutions • Requirements for applying for off-site waiver • 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 • Names or initials • All geographic subdivisions smaller than state • All elements of dates except year; all ages > 89 • Telephone numbers • Fax numbers • E-mail addresses • Social Security numbers (or scrambled SSNs) • Medical record numbers • Health plan beneficiary numbers

31. 18 HIPAA Identifiers (cont’d) • Account numbers • Certificate or license numbers • Vehicle identifiers • Device identifiers and serial numbers • URLs • IP addresses • Biometric identifiers, including finger and voice prints • Full-face photographs and any comparable images • Any other unique identifyingnumber, 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 beforebanking 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 (Marilyn.Mason@va.gov); 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: Marilyn.Mason@va.gov • Phone: 202/ 254-0496 • Fax: 202/ 254-0521