1. Implications for the Use of Tissue in Research P. Pearl O’Rourke, MD Partners HealthCare Boston, MA

2. The Context Tissue is/has always been an important resource for biomedical education and discovery Tissue has become an even more valuable resource as a result of: –Genetic Research –Personalized Medicine

3. Consider the researcher What researchers ideally want: –Large numbers of tissue specimens that are identifiable and updated in perpetuity with medical, social and environmental information that can be used for broad research uses What researchers often accept: –‘De-identified’ tissue specimens Linked Anonymized

4. Consider the researcher What researchers give-up –Potentially valuable updated clinical information –Environmental data –Ability to re-contact individuals Why they are willing to compromise –Cost and logistics of obtaining identifiable specimens (informed consent) –Remember they need large numbers

5. Consider the tissue source Increasing request/demand for –Recognition of ownership of specimens –Control over use/s –Participatory research –Information about research results and findings Evidence that my tissue/data was in fact used What was found Return of research results – individual as well as aggregate

6. Consider the IRB Existing challenges of consent –Too long; too complicated; too legalistic –Too often not even remembered –Add the issues of tissue acquisition Often an ‘add-on’ to another protocol Distance between individual and researcher Distance between consent and tissue use What is identifiable? –Living with a regulatory paradigm that is driven by identifiability

7. Consider the IRB Genetic risk assessment –Community risk Return of research results Data sharing The regulatory and ethical oversight of tissue research is under scrutiny Recent events in the news

8. The Immortal Life of Henrietta Lacks Rebecca Skloot The origin of the HeLa cell line Extra biopsies taken for research purposes – without consent or knowledge of the patient or her family Biopsies taken in the 1950s – prior to the creation of IRBs

9. Newborn Blood Spots (NBS) State-specific programs for diagnosis of specific diseases in neonatal period In some states the NBSs were kept and made available for research purposes Fact: –These NBSs are an invaluable research resource –Status of consent/knowledge of – at best variable

11. The Havasupai Settlement Adequacy of consent –Individual as well as community –For primary use/s –For secondary use/s Control of specimens Researchers’ responsibility to participants Genetic concern –Perhaps exceptionalism Community Risk Assessment

12. So… How are specimens obtained for research? –Specifically for research purposes –Left-over clinical specimens What are the relevant regulations?

13. The Regulations Common Rule 45 CFR 46 FDA Regulations –re: human subjects in research Health Insurance Portability and Accountability Act (HIPAA)

14. The Common Rule Definition of Human Subject –Human subject means a living individual about whom an investigator (whether professional or student) conducting research obtains Data through intervention or interaction with the individual, or Identifiable private information.

15. Why was the tissue /data obtained? For researchFor clinical care THE RESEARCH LAB How Your Tissue/Data May Get to a Research Lab Informed Consent Known donation Unknown donation

16. Why was the tissue /data obtained? For researchFor clinical care THE RESEARCH LAB How Your Tissue/Data May Get to a Research Lab Informed Consent Known donation Unknown donation De-identified

17. Why was the tissue /data obtained? For researchFor clinical care Is there excess tissue? NOYES Is it identifiable? NOYES Informed consent NO YES THE RESEARCH LAB How Your Tissue/Data May Get to a Research Lab Known donation Unknown donation

18. Why was the tissue /data obtained? For researchFor clinical care Is there excess tissue? NOYES Is it identifiable? NOYES Informed consent NO YES THE RESEARCH LAB How Your Tissue/Data May Get to a Research Lab Informed Consent Known donation Unknown donation De-identified

19. Why was the tissue /data obtained? For researchFor clinical care Is there excess tissue? NOYES Is it identifiable? NOYES Informed consent NO YES THE RESEARCH LAB How Your Tissue/Data May Get to a Research Lab Informed Consent Known donation Unknown donation De-identified Human Subjects Research

20. What this means in practice Existing tissue/data, if not identifiable –Not a human subject –No worry about consent (Common Rule) –No worry about authorization (HIPAA) If identifiable –Yes, a human subject –IRB must determine need for consent –Privacy Board (IRB) must determine need for authorization (HIPAA)

21. In Practice We spend much time trying to define identifiability –C –Common Rule –HIPAA –Evolving identifiability standards related to: Data mining Genetic information

22. Is it IDENTIFIABLE? YESNO

23. Is it IDENTIFIABLE? YESNO

24. Is it IDENTIFIABLE? YESNO

25. Is it IDENTIFIABLE? YESNO HIPAA Common Rule State Laws Institutional Policies

26. Perhaps a Disconnect? People want to know how their data and tissue are being used in research Some want to control how their data and tissue are being used. People are NOT impressed with the use of ‘identifiability’ as the trigger for oversight

27. Specific Disconnects Informed consent –Particular issues in tissue banking Communication –Updates re: the research activities in general The category of tissue research that is considered not human subjects research AND besides – are we at a point that all tissue should be considered identifiable?

28. So where do we go from here ? Option 1: Maintain the status quo –Improve consent process Relook at broad consent Ongoing consent –Educate clinicians, researchers, and the public –Notification

29. So where do we go from here ? Option 2: Consider all tissue identifiable and maintain the regulatory status quo –All tissue uses would be considered HS research – HUGE burden for IRBs with likely little gain in terms of benefit –In reality transparency for the public would NOT improve – most protocols would have a waiver of informed consent

30. So where do we go from here ? Option 3: Consider all tissue identifiable and re-evaluate and potentially modify the regulatory process –Do we need more than the Common Rule? –Develop alternate levels of review for categories of tissue research that is usually very low risk research –Consider new models of notification and/or consent

31. So where do we go from here ? At the least we need: –Broad-based discussion with all interested parties with the goal of developing common practices for today and the future Patients and research participants Clinicians and researchers Relevant Government agencies Professional Societies Banking professionals Others