1. Update on VA Human Specimen Research and Tissue Banking
Marianna J. Bledsoe, M.A.
Senior Program Manager for Biorepositories and Biobanking
Office of Research and Development
June 27, 2012

2. Note: To see the answers to the survey questions, you must view this as a PowerPoint slide show. There are no “correct” answers for this presentation. This was a poll.

3. Overview Introduction Audience response questions
Applicable federal regulations
Relevant VA policies
VA guidelines
Other Considerations for ACOS/R&D and AO

4. For ACOS Only: Do you currently have approved research projects involving human specimens research at your facility?
Yes No
Unknown

5. For ACOS Only: Do you have human “tissue banks*” at your facility?
Yes No
Unknown
*For the purposes of this presentation, a tissue bank is a repository of specimens established and maintained for the purposes of secondary or future research.

6. For ACOS only: Do investigators at your facility have projects in which specimens are banked off-site?
Yes No
Unknown

7. For ACOS only: If you answered yes to the preceding question, where are the specimens located?
Academic affiliate
Other location other than academic affiliate
Both of the above
Unknown

8. TIME Magazine’s Top 10 Ideas Changing the World Right Now
Jobs Are the New Assets
Recycling the Suburbs
The New Calvinism
Reinstating The Interstate
Amortality
Africa: Open for Business
The Rent-a-Country
Biobanks
Survival Stores
Ecological Intelligence
March 16, 2009 Issue

9. Media Reports of Cases Involving Human Specimens

10. Federal Regulations and Policies Related to Human Specimen Research

11. Applicable Federal Regulations May Include:
Common Rule: 38 CFR part 16
FDA Regulations:
21 CFR Part 50, 56, 812
HIPAA Privacy and Security Rules:
45 CFR Part 160; Subparts A, C & E of Part 164
Privacy Act of 1974
HITECH Breach Notification Interim Final Rule
Provide links in the handouts

12. When is Specimen Research Human Subjects Research According to the Common Rule?
Is it research?
Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.
OHRP considers creation of repositories for research purposes/tissue banks a research activity

13. When is Specimen Research Human Subjects Research According to the Common Rule?
Is it human subjects research?
Human subject – A living individual about whom an investigator (whether professional or student) conducting research obtains a) data through intervention or interactions with the individual, or b) identifiable private information. [38 CFR (f)]
Common Rule definition of identifiable = the identity of the subject is or may readily be ascertained by the investigator or associated with the information

14. Three paths to human subjects research under 38 CFR part 16:
When is research involving a tissue bank human subjects research according to the Common Rule?
Three paths to human subjects research under 38 CFR part 16:
Creating a research tissue bank through intervention or interaction with individual
Creating a research tissue bank by obtaining identifiable private information
Obtaining identifiable private information from a research tissue bank

15. Is research using “coded” specimens human subjects research according to the Common Rule? It depends.

16. OHRP Guidance on Coded Private Information or Biological Specimens
Definition of “Coded”:
(1) identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol, or combination thereof (i.e., the code); and
(2) a key to decipher the code exists, enabling linkage of the identifying information to the private information or specimens.

17. OHRP Guidance on Coded Private Information or Biological Specimens
“In general, OHRP considers private information or specimens to be individually identifiable as defined at 45 CFR (f) when they can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems.”
However, the OHRP coded specimens policy allows exceptions under certain conditions.

18. OHRP Guidance on Coded Private Information or Biological Specimens
Research involving only coded information or specimens is not considered to involve human subjects if the following conditions are both met: (1) the private information or specimens were not collected specifically for the currently proposed research project through an interaction or intervention with living individuals; AND (2) the investigator(s) cannot readily ascertain the identify of the individual(s) to whom the coded private information or specimens pertain.

19. OHRP Guidance on Coded Private Information or Biological Specimens
Examples of When Coded Data/Biologic Specimens Are Not Individually Identifiable to Investigators: (a) the investigators and the holder of the key enter into an agreement prohibiting the release of the key to the investigators under any circumstances, until the individuals are deceased

20. OHRP Guidance on Coded Private Information or Biological Specimens
Examples of When Coded Data/Biologic Specimens Are Not Individually Identifiable to Investigators:
(b) there are IRB-approved written policies and operating procedures for a repository or data management center that prohibit the release of the key to the investigators under any circumstances, until the individuals are deceased; or
(c) there are other legal requirements prohibiting the release of the key to the investigators, until the individuals are deceased.

21. OHRP Guidance on Coded Private Information or Biological Specimens
Only applies if: 1. Person(s) doing coding of data/specimens and person(s) holding codes are not part of the research team; AND 2. Specimens/data are not being obtained for the specific research in question by an interaction or intervention with living individuals.

22. Review of VA Human Specimen Research
When human specimens are used in VA research, the research must be included as part of a protocol that is reviewed and approved by the VA R&D Committee.
If the research involving human specimens is human subjects research according to the Common Rule or FDA regulations, the research must also be reviewed and approved by an IRB.

23. VA Specimen Research
Current guidelines found on ORD web site
VHA Handbook on specimen research/tissue banking currently under development

24. Relevant VA Policies
VHA Handbook Requirements for the Protection of Human Subjects in Research
VHA Handbook —Use of Data and Data Repositories in VHA Research
VHA Handbook Privacy and Release of Information
VHA Handbook —Minimum Necessary Standard for Protected Health Information
VA Handbook Information Security Program
VHA Handbook —Pathology and Laboratory Medicine Service Procedures

25. Current VA Guidelines

26. Case Example #1
An investigator is collaborating with a drug company that is collecting specimens as part of an industry sponsored trial. The drug company will be performing analyses for the main study, but will be retaining specimens less than 90 days.

27. Is an off-site waiver from ORD needed?
Yes No
Don’t Know

28. Case Example #2
An investigator is collaborating with a drug company that is collecting specimens as part of an industry sponsored trial. The drug company will be performing analyses for the main study, and will be storing the specimens for the entire length of the study (5 years).

29. Is an off-site waiver from ORD needed?
Yes No
Don’t Know

30. Case Example #3
An investigator is collaborating with a drug company that is collecting specimens as part of an industry sponsored trial. The drug company will be performing analyses for the main study, and wishes to bank the specimens beyond the end of the study protocol for future unspecified research.

31. Is this permitted by current VA guidelines?
Yes No
Don’t Know

32. Specimens for a Single Research Protocol
A waiver from ORD must be obtained if:
If specimens are stored off-site at a non-profit institution 5 years
If specimens are stored off-site at a non-academic, for-profit institution for >3 months
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.

33. Collecting and Storing Specimens for Secondary or Future Research (“Tissue Banking”)
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 be aware of all tissue banks within the facility.

34. Collecting and Storing Specimens for Secondary or Future Research
The researcher must obtain a waiver from ORD before banking human biological specimens for future research use at an off-site location.
Specimens may not be banked for future research use at a non-academic, for-profit institution.
Off-site tissue banks are approved on a per protocol basis.

35. Collecting and Storing Specimens for Secondary or Future Research
Exception: Some National Cancer Institute (NCI)-sponsored tissue banks are exempt from the requirements as a result of a memorandum of understanding with the NCI. Protocols that involve collection for these banks do not require ORD approval. (See list on VA tissue banking website)

36. Storage of Specimens
Specimens must be labeled with a code that does not contain any of the 18 HIPAA identifiers.
In the case of storage at non-profits, the key to the code must be maintained at the VA unless there is a compelling reason otherwise. If the storage is at a for-profit institution, then it is mandatory that the code be maintained at the VA.

37. Additional Requirements for Specimens Stored at For-Profit Sites
Only analyses/tests listed in the protocol and informed consent may be performed.
The code must be maintained at the VAMC.
All specimens must be de-identified to meet both Common Rule and HIPAA requirements.
Limited DNA/RNA analyses may be performed.

38. Additional Requirements for Specimens Stored at For-Profit Sites (Cont’d)
Use of initials outside of VA is generally not permitted.
Specimens must be destroyed within 1 year of the study completion date. The company should inform the PI in writing when samples are destroyed.

39. Application Process for All Off-site Waivers
The investigator must complete VA form (
The following additional is required:
Research protocol
Tissue bank manual/SOPs [non-profits]
VA consent form
HIPAA authorization
The application should be ed to Kristina Hill It should be sent from the research office.
Alternatively, the form and requested information can be faxed to: (202)

40. Application Process for All Off-site Waivers
After the application is reviewed, the PI and ACOS/R will receive a memo listing any issues that need to be addressed.
Frequent issues with all waiver applications include informed consent issues and use of identifiers.
Frequent issues with waivers for off-site storage at for-profits include requests for long term storage and mandatory banking or genetic testing which is not permissible except when integral to study design.

41. 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 an off-site storage waiver.

42. Other Points to Consider for ACOS/R&D and VA/AO

43. Custodianship
VA investigators and their facilities have a caretaking responsibility for the management of specimen collections.
Includes tracking of documentation, ensuring that policies are in place and implemented appropriately, establishing agreements when specimens are transferred to third parties, and ensuring that specimens are appropriately disposed of when the collection is no longer scientifically useful or can no longer be maintained.

44. Custodianship
A VA investigator should be designated as the custodian of specimen collections in the protocol that is reviewed and approved by the R&D Committee. (Requirement for off-site storage waiver).
Physical safeguards and policies should be in place to restrict access to only authorized individuals who need access to perform their duties under the approved research protocol.

45. Custodianship
Specimens should only be transferred outside of VA when such transfers are consistent with the R&D Committee and IRB-approved protocol and informed consent and there are appropriate agreements in place that define the responsibility of the specimen recipients.
Material Transfer Agreements (MTAs), Cooperative Research and Development Agreements (CRADAs), or other contractual agreements that define the responsibilities of the recipient

46. Material Transfer Agreements
Address:
Appropriate use of specimens (consistent with protocol and informed consent, etc.)
Human subjects protections
Sharing of specimens with third parties
Commercial use of specimens
Biohazards
Indemnification

47. Need to address custodianship issues:
Special Considerations When Specimens Are Collected For Storage and Distribution for Future Research (“Tissue Banking”)
Need for review and oversight of tissue bank operating procedures and policies for protecting subject privacy and confidentiality, access and dissemination
Need for mechanism for ensuring specimen use is consistent with informed consent
Need to address custodianship issues:
Material Transfer Agreements; CRADAs
Plans if repository/bank loses support or is no longer scientifically useful
Plans for transfer if PI leaves institution

48. Current Hot Topics Return of Research Results and Incidental Findings
Topic of considerable controversy, especially in the context of tissue banking
Group Harms
Identifiability
Differing definitions
Impact of emerging genetic technologies and extent and availability of databases containing patient/subject information

49. Stay Tuned: Change is On the Way
VHA Handbook currently under development
Current VA guidelines may change
Common Rule may change
More to come!

50. Resources and Best Practices
See handouts on meeting website:
Regulations, Policies and Educational Documents Related to Human Specimen Research
Resources and Tools Related to Human Specimen Research
2012 Best Practices for Repositories: Collection, Storage, Retrieval, and Distribution of Biological Materials for Research. International Society for Biological and Environmental Repositories; Biopreservation and Biobanking, 10(2), 2012.
National Cancer Institute Best Practices for Biospecimen Resources,

51. Questions?

52. Acknowledgements
Kristina Hill, MPH, MT(ASCP)

53. Contact Information
Marianna Bledsoe, MA
Senior Program Manager for Biorepositories and Biobanking
Phone:
Kristina Hill, MPH, MT(ASCP)
Health Science Specialist
Phone: