Genomic Medicine Program Ronald M. Przygodzki, MD Associate Director, Genomic Medicine ORD March 2008

1. Genomic Medicine ProgramRonald M. Przygodzki, MDAssociate Director, Genomic Medicine ORDMarch 2008

2. What is Genomic Medicine? • Genomic Medicine (personalized medicine) is healthcare tailored to an individual based on their genetic makeup (genes). • Genes are the basis for all our characteristics. • There are about 25,000 genes in a human cell. • In 2003, the entire human genome was sequenced. • This has resulted in an explosion in new and advanced technologies.

3. VA Genomic Medicine Program • VA launched the Genomic Medicine Program in 2006 to • Optimize medical care for veterans (for example, avoid adverse drug reactions) • Enhance development of tests and treatments for relevant diseases • Examine the potential of emerging genomic technologies

4. VA Genomic Medicine Program (cont’d) • VA is uniquely positioned to implement the genomics medicine program • Largest healthcare system in the US, providing care for >5.3 million veterans • Equipped with an unrivaled electronic medical record system • Stable and diverse patient population

5. VA Genomic Medicine Program (cont’d) • Veterans may volunteer to participate • Provide blood sample for genetic analysis • Genetic information linked to their electronic health records

6. Implementation • 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

7. Veteran Consultation Project • 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.

8. 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

9. Focus Groups • Knowledge and attitudes about genomic medicine • General acceptability of proposed goals and methods of VA genomic studies • Areas of concern • Methods of recruitment and consent issues • Role of Veteran Service Organizations (VSOs) • Expectations of potential participants with regard to confidentiality, privacy, and security • Use of research findings • Return of results, ongoing communication, etc.

10. Focus Groups (cont’d) • Nine focus groups were conducted (10-12 participants in each group). • Focus group guides and questions were developed in consultation with VACO.

11. Focus Groups (cont’d) • Veterans were recruited from: • Local chapters of VSOs that reflect the 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

12. Focus Groups (cont’d)

13. Initial Observations from Focus Groups • Areas of optimism include: • Altruism and a sense of community • No expectations of compensation for participation • Community leaders to voice their opinions/concerns • Appreciative of being consulted • Generally knowledgeable about genetics

14. Initial Observations from Focus Groups (cont’d) • Areas of concern include: • Trust issues • Data privacy, security, and access • Data sharing (trusted VA and academic researchers but not the commercial sector) • Loss of benefits

15. 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 VA

16. 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.

17. 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

18. 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.

19. 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

20. Infrastructure Development • DNA Bank/Biorepository (Boston VA) • About 30,000 blood samples collected as part of CSP trials • Pharmacogenomics Analysis Laboratory (Little Rock) • Educational tools—collaboration between VA Employee Education Resource Center and National Coalition ofr Health Professionals Education in Genetics (NCHPEG) • Assessing current capabilities and activities related to genomics at VAMCs

21. 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

22. Studies in Planning • Serious Mental Illness 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 • Genome-wide association studies • Variants that contribute to functional disability • Responsiveness to therapy • Drug toxicity

23. Studies in Planning (cont’d) • PTSD Genetics Working/Planning Group • 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.

24. 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)

25. Tissue Banking Policies January 2008

26. Topics Covered • Definitions of human biological specimens, banked specimens, and de-identified • On-site tissue banks • Off-site tissue banks • Specimens stored at non-academic, for-profit institutions • Applying for an off-site waiver • Elements required in an informed consent

27. Human Biological Specimens • Any material derived from a human subject—such as blood, urine, tissues, organs, hair, nail clippings, or any other cells or fluids • Whether collected for research purposes or as residual specimens from diagnostic, therapeutic, or surgical procedures

28. Banked Specimens • Biological specimens collected and stored for future research purposes that are beyond the scope of work described in the original protocol and informed consent OR • Biological specimens collected under a protocol designed for banking of specimens

29. Non-Banked Human Biological Specimens Human biological specimens collected under a VA-approved protocol that are used for only the specific purposes defined in the protocol and are destroyed when the specific testing/use is completed or at the end of the protocol • Important Notes: • If specimens are stored off-site at a non-profit institution 5 years, then the investigator must obtain a waiver from ORD. • If specimens are stored off-site at a non-academic, for-profit institution for >3 months, a waiver must be obtained from ORD.

30. Non-Banked Specimens • If the specimens are sent to a non-VA institution for testing as defined in the protocol, once the specific analyses are performed, the remainder of the specimens must be destroyed or returned to the VA for destruction. • If the specimens are destroyed at another institution, that institution must certify the destruction of the specimens in writing.

31. De-identified De-identified data is health or other information about an individual that: • Does not contain any of the 18 HIPAA identifiers AND • Is de-identified according to the Common Rule Coded information is not considered de-identified if the tissue bank or data coordinating center has access to the codes.

32. HIPAA Identifiers • Names or initials • All geographic subdivisions smaller than a state • All elements of dates except the year and all ages over 89 • Telephone numbers • Fax numbers • E-mail addresses • Social Security numbers (or scrambled SSNs) • Medical record numbers • Health plan beneficiary numbers

33. 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

34. On-Site Tissue Banks • A tissue bank established at a VA site by a VA-paid investigator does not require ORD approval. • The ACOS/R or research office should maintain records of all tissue banks within the facility.

35. On-Site Tissue Banks (cont’d) • If a VA site does not have the resources to bank specimens, then they may be banked at any VA site that has an established tissue bank. • Alternatively, specimens may be banked at the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) core laboratory at the Boston VA. It serves as the Cooperative Studies Program (CSP) Genetic Tissue Core Laboratory. • Either option is considered on-site banking.

36. Off-Site Tissue Banks • The researcher must obtain a waiver from ORD before banking human biological specimens at an off-site location. • Off-site tissue banks are approved on a per protocol basis. • Exception: National Cancer Institute (NCI)-sponsored cooperative tissue banks listed on the next slide. As a result of a letter of understanding with the NCI, these banks are designated as VA-approved if they are used for one of their protocols (for example, the SWOG-supported tissue bank can be used for SWOG protocols without ORD approval).

37. 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) • National Cancer Institute of Canada Clinical Trials Group(NCIC CTG) • Cooperative Breast Cancer Tissue Resource • Cooperative Human Tissue Network • Gynecologic Oncology Group Tissue Network • Cancer Prevention Network

38. Banked Specimens • Specimens may not be banked at a non-academic, for-profit institution • Specimens must be labeled with a code that does not contain any of the 18 HIPAA identifiers. • The key to the code must be maintained at the VA unless there is a compelling reason otherwise.

39. Data Related to Banked Specimens • If data linked to the sample leaves the VA, then it must be de-identified or stored in a database that is encrypted according to FIPS 140-2 standards. • See VA Handbook 6500 “Information Security.”

40. Non-Banked Specimens Stored at Non-Academic For-Profit Sites • If the specimens are held for >3 months, then a waiver must be obtained from ORD. • Only analyses/tests listed in the protocol and informed consent may be performed. • The code must be maintained at the VAMC. • All specimens and associated data must be de-identified. • DNA and RNA may not be analyzed. • The company must inform the PI in writing when samples are destroyed.

41. Non-Banked Specimens Stored at Non-Academic For-Profit Sites (cont’d) • HIPAA authorization must expire. • Case reports may not contain initials if they leave VA. • Specimens must be destroyed upon request of the subject. • Before company personnel may view files at the VA, they must complete VA security and privacy training. • Specimens must be destroyed within 1 year of the study completion date.

42. Application Process • The investigator must complete VA form 10-0436. This is a pdf form that can be filled in and saved using Acrobat Reader version 7 or higher (http://www.va.gov/vaforms/medical/pdf/vha-10-0436-fill.pdf). • The information requested on page 5 of the application can be scanned and attached to the pdf or to the e-mail. • Biographical sketch of the PI • Research protocol • Tissue bank manual or SOPs • VA consent form

43. Application Process (cont’d) • The application should be e-mailed to Marilyn Mason (Marilyn.Mason@va.gov). The ACOS/R must be carbon copied. • Alternatively, the form and requested information can be mailed to the address given on the form.

44. Application Process (cont’d) • After the application is reviewed, the PI and ACOS/R will receive a memo listing any issues found with the application. Frequently, the informed consent needs to be modified.

45. Multi-Site Trials • If several VAMCs are planning to participate in the same clinical trial, then only one of the VA sites needs to apply for a waiver. • A list of multi-site clinical trials in which more than one VAMC is participating is posted on the VA R&D web site. (http://www.research.va.gov/programs/tissue_banking)

46. Informed Consent • Several elements must be included in an informed consent when the protocol involves banking–either on-site or off-site– of human biological specimens. • The elements are important for transparency to the subject. • The list of elements is posted on the VA R&D web site, and some are given on the next slide.

47. Informed Consent (cont’d) • Some informed consent elements • Types of samples stored and length of time to be stored • Name and location of tissue bank • Types of future studies • Subject may withdraw from the study and request that his/her samples be destroyed • If the specimen will be shared with other researchers for approved research protocols

48. Informed Consent (cont’d) • The informed consent does not need to narrowly specify the future uses of the banked specimens. • But if it is not specific, in the consent form or during the consent process, the PI should explain what such phrases as “related diseases” or “unspecified research” means for the use of the sample and the impact on the subject.

49. Contact Information • For additional information and questions, contact Marilyn Mason • E-mail: Marilyn.Mason@va.gov • Phone: 202-254-0496 • Fax: 202-254-0521