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

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

THE BANK Specimen Source Specimen Recipient

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

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

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

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

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

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

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

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

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

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

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

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: http://www.primr.org/uploadedFiles/PRIMR_Site_Home/Public_Policy/Recently_Files_Comments/Tissue%20Banking%20White%20Paper%203-7-07%20final%20combined.pdf

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

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

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

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.

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.

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.

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

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. .

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.

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

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.

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. .

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.

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. .

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. .

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. .

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

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.

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.

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.

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.

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