1. TISSUE BANKING Challenging to Say the Least
P. Pearl O’Rourke, M.D.
Director, Human Research Affairs
Partners HealthCare System
Boston, MA

2. Agenda The Complexity of banking PRIM&R White Paper on Tissue Banking
Introduction
Identified Barriers and Recommendations
Other ‘gnarly’ issues

3. THE BANK
Specimen
Source
Specimen
Recipient

4. Bank Issues to Consider
What does it look like?
Single site
Multiple branch sites
Loosely affiliated cooperating banks with centralized coordination
Virtual bank
The ‘Owner’ or Responsible Party
Academic Medical Center; for-profit entity; advocacy foundation; government agency;
HIPAA entity or not

5. Bank Issues to Consider
What is banked
Disease-specific focus or no focus
Clinical and/or research specimens
Associated data
Identifiable; limited data set; coded or anonymized
Processing of specimens
Validation of diagnosis or other processing
Updating with future medical data and/or research results

6. The Specimen Source Who can provide specimens to the bank?
Any clinician or investigator
Only ‘approved’ clinicians and investigators
Type of specimens that will be accepted
Obtained during clinical care (excess)
Obtained for research purposes
Solely for research
Extra obtained during clinical care

7. The Specimen Source
What data will be collected and subsequently submitted to the bank?
Specimens collected with identifiable information
Sent to bank with identifiers
Sent to bank with limited data set
Sent to banks coded – link remaining at source
Sent to bank anonymized
Specimens collected with limited data set
Specimens collected with no identifiers

8. The Specimen Source What permissions will be obtained?
Informed consent (Common Rule/FDA Regs)
Authorization (HIPAA)
Who will obtain permission?
Any clinician
Any researcher
Only bank affiliated persons

9. The Specimen Recipient
Who can access specimens?
Anyone
Access restricted based on; e.g., affiliation with the bank; domestic vs international; not-for-profit vs commercial entity.
What can be accessed?
Specimens with identifiable information; coded data; limited data set; no data

10. The Specimen Recipient
Can a recipient re-contact a tissue donor or have access to individual medical records?
If yes, with what review and approval?
How does the bank decide who is ‘worthy?’
Ethical use
Consistency with initial informed consent/authorization
Trivial research with limited specimens

11. THE BANK Specimen Source Specimen Recipient IRB Review IRB Review
Informed Consent
Authorization
IRB Review
Informed Consent
Authorization

12. Identifiable Tissue Tissue Source Tissue Recipient Tissue Bank with
IRB approval 3
Tissue Bank with
Identifiable Tissue
Identifiable tissue 1
Tissue obtained solely for research 4
Coded tissue 2 5
Tissue originally collected for clinical care
Limited Data Set 6
Anonymous/ anonymized
IRB approval - informed consent/authorization or waiver*
No additional IRB approval - letter of agreement.
No additional IRB approval – Data Use agreement
No additional IRB approval
IRB approval - informed consent/authorization 3 1 4 2 5
*Specific Consent at 1 or 2 will usually suffice 6

13. No Identifiable Tissue
Tissue Source
Tissue Recipient
IRB approval
Tissue Bank with
No Identifiable Tissue 1
Tissue obtained solely for research 2
De-identified tissue Anonymous/ anonymized
Tissue originally collected for clinical care 1
IRB approval - informed consent/authorization
No additional IRB approval and no letter of agreement 2

14. Report of the Public Responsibility in Medicine and Research (PRIM&R) Human Tissue/Specimen Banking Working Group
Part I: Assessment and Recommendations
Part II: Tools for Investigators, IRBs and
Repository Managers
March 2007

15. Available on the PRIM&R Website:
Report of the Public Responsibility in Medicine and Research (PRIM&R) Human Tissue/Specimen Banking Working Group
Available on the PRIM&R Website:

16. Purpose PRIM&R Tissue Banking Working Group
To identify
Current barriers to the collection, storage, distribution, and use of human specimens and data in research
Strategies for overcoming these barriers while protecting subjects

17. Participants PRIM&R Tissue Banking Working Group
IRB members
Lawyers
Ethicists
Researchers
Repository managers
Patient advocates
Representatives from academia, industry and government

18. Barrier 1 PRIM&R Tissue Banking Working Group
Diversity of banks and confusion about what types of banking activities constitute research activities or human subjects research under existing regulations

19. Barrier 1 Recommendations to Federal Regulatory and Funding Agencies
A. OHRP should provide criteria for and examples of when a “collection” of human specimens is considered a research activity under the Common Rule. Specific attention should be paid to multiple-use and research support collections. OHRP should re-evaluate whether the mere collection of excess specimens for possible future use constitutes research for the purposes of regulatory oversight.

20. Barrier 2 PRIM&R Tissue Banking Working Group
Lack of single comprehensive ethical and regulatory framework that addresses the full spectrum of activities related to specimen banking and use. The current situation is a patchwork of regulations and guidance addressing the collection, storage, distribution, and use of human specimens and associated data.

21. Barrier 2 Recommendations to Federal Regulatory and Funding Agencies
B. OHRP, FDA, NIH, and other relevant federal funding agencies should work with other stakeholders (e.g., researchers, repository managers, IRBs, lawyers, ethicists, patient advocates, and research subjects) to develop a comprehensive framework for the collection, banking, and use of human specimens in research.

22. Barrier 3 PRIM&R Tissue Banking Working Group
Lack of harmony among federal regulations.

23. Barrier 3 Recommendations to Federal Regulatory and Funding Agencies
C. Federal regulatory and funding agencies should develop standardized language and definitions for use in regulations, policy documents, and educational materials related to specimen banking.
D. FDA should explore whether there are ways to more closely align the FDA definition of human subject with the Common Rule definition, which requires obtaining data through a research intervention or interaction or the use of individually identifiable information. .

24. Barrier 3 Recommendations to Federal Regulatory and Funding Agencies
OHRP should define more specifically when research using human specimens and associated data is or is not human subjects research and when it is exempt under the Common Rule. Case studies and examples would help clarify the confusion in this area.
DHHS should modify the Privacy Rule to exempt all research that is exempt under the Common Rule.

25. Barrier 4 PRIM&R Tissue Banking Working Group
Misunderstanding and over-interpretation of the risks associated with the banking and use of specimens.

26. Barrier 4 Recommendations to Federal Regulatory and Funding Agencies
OHRP should develop additional guidance to help IRBs assess the level of risk related to the collection, storage, distribution, and research use of specimens and associated data.
DHHS/OCR should work with OHRP to develop additional guidance to help IRBs and Privacy Boards evaluate risks to privacy and confidentiality with a view toward improving consistency of subject privacy protections.

27. Barrier 4 Recommendations to Federal Regulatory and Funding Agencies
Federal regulatory and funding agencies should work with appropriate stakeholders to develop additional educational materials for IRBs, patients and the public about how to evaluate the benefits and risks of participation in genetics research on human specimens. .

28. Barrier 5 PRIM&R Tissue Banking Working Group
Differing and confusing regulatory requirements for obtaining informed consent for the use of specimens in research and the HIPAA Privacy Rule requirement for authorization for the research use of protected health information.

29. Barrier 5 Recommendations to Federal Regulatory and Funding Agencies
OHRP should issue guidance clarifying when waiver of informed consent for collection, storage, distribution, and use of specimens in research is appropriate. This should include:
guidance on determining when research using biological specimens is minimal risk
guidance on interpreting the “practicability” requirement for waiver of informed consent. .

30. Barrier 5 Recommendations to Federal Regulatory and Funding Agencies
OHRP should provide additional guidance about the use of generalized informed consent for future research use of specimens and associated data and develop acceptable consent models for specimen banking.
FDA should explore additional approaches to permit specimens and data to be used without consent for minimal risk research. .

31. Barrier 5 Recommendations to Federal Regulatory and Funding Agencies
DHHS/OCR should explore approaches for removing the requirement that the authorization for research use of protected health information obtained from a research repository or database be study-specific.
The Privacy Rule should be revised to allow authorization for use of protected health information collected as part of a clinical trial to cover both research and banking activities.
The Privacy Rule requirement to account for disclosures of protected health information pursuant to a waiver of authorization should be eliminated. .

32. Barrier 6 PRIM&R Tissue Banking Working Group
Practical implementation issues related to informed consent and authorization.

33. Barrier 6 Recommendations to Federal Regulatory and Funding Agencies
Funding agencies should support infrastructure to enable institutions to implement processes for routinely obtaining and tracking informed consent for future research use of specimens obtained during the course of medical care.
OHRP should consider the acceptability of using alternative approaches to informed consent, such as ‘opt out’ notification, as a tool to be used in concert with a waiver of consent for future research on residual specimens.

34. Barrier 7 PRIM&R Tissue Banking Working Group
The HIPAA Privacy Rule imposition of additional requirements for research that is covered by the Common Rule, adding unnecessary burden to patients, researchers, IRBs and institutions.

35. Barrier 7 Recommendations to Federal Regulatory and Funding Agencies
DHHS should modify the Privacy Rule to exempt research that is subject to the Common Rule because the Common Rule provides appropriate and equivalent protections.

36. Barriers not addressed, that merit further discussion
Lack of clear guidance about how to deal with the complex issues of ownership of specimens, intellectual property considerations with regard to discoveries made using specimens
Whether research results should be returned to subjects and if so, how and when.

37. Other Gnarly Issues Assessing community risk Specimens from children
When minor become majors