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

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.

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

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

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.

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

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

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Media Reports of Cases Involving Human Specimens

Federal Regulations and Policies Related to Human Specimen Research

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

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

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 16.102(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

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

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

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.

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 46.102(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.

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.

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

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.

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.

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.

VA Specimen Research Current guidelines found on ORD web site http://www.research.va.gov/programs/tissue_banking/default.cfm VHA Handbook on specimen research/tissue banking currently under development

Relevant VA Policies VHA Handbook 1200.05--Requirements for the Protection of Human Subjects in Research VHA Handbook 1200.12—Use of Data and Data Repositories in VHA Research VHA Handbook 1605.1--Privacy and Release of Information VHA Handbook 1605.2—Minimum Necessary Standard for Protected Health Information VA Handbook 6500--Information Security Program VHA Handbook 1106.01—Pathology and Laboratory Medicine Service Procedures

Current VA Guidelines

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.

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

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).

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

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.

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

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.

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.

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.

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)

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.

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.

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.

Application Process for All Off-site Waivers The investigator must complete VA form 10-0436. (http://www.va.gov/vaforms/medical/pdf/vha-10-0436-fill.pdf). The following additional is required: Research protocol Tissue bank manual/SOPs [non-profits] VA consent form HIPAA authorization The application should be e-mailed to Kristina Hill (Kristina.Hill@va.gov). It should be sent from the research office. Alternatively, the form and requested information can be faxed to: (202) 495-6156.

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.

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.

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

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.

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.

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

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

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

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

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

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, http://biospecimens.cancer.gov/practices/

Questions?

Acknowledgements Kristina Hill, MPH, MT(ASCP)

Contact Information Marianna Bledsoe, MA Senior Program Manager for Biorepositories and Biobanking E-mail: Marianna.Bledsoe@va.gov Phone: 202-443-5781 Kristina Hill, MPH, MT(ASCP) Health Science Specialist E-mail: kristina.hill@va.gov Phone: 202-443-5675