Subcommittee on the Inclusion of Individuals with Impaired Decision-making in Research (SIIIDR)

1. Subcommittee on the Inclusion of Individuals with Impaired Decision-making in Research(SIIIDR) Report to SACHRP October 29, 2007 Laurie Flynn and David H. Strauss, M.D., co-chairs

2. Overview • Review of charge • Describe SIIIDR’s strategy and review progress • Question: how can SACHRP most effectively “advise, consult and make recommendations” in order to “improve functions within the authority of HHS” on the specific matter of the “legally authorized representative”?

3. From the SACHRP Charter The committee shall advise, consult with, and make recommendations on matters pertaining to…protections for human subjects in research… with special emphasis on special populations, such as…the decisionally impaired

4. From the SIIIDR Charge The Subcommittee will develop recommendations for consideration by SACHRP about whether guidance and/or additional regulations are needed for research involving individuals with impaired decision-making capacity.

5. Opportunity Statement • We emerged, some thirty years ago, from a period in which research with captive, incompetent and vulnerable populations was commonplace; • Prior efforts on the federal level to craft specific protections for those who are unable to consent have not been successful; • As a result, there is a genuine void in regulatory coverage where pressing research questions involving these most vulnerable subjects are at issue. • While the specific consequences of this void have not been well-documented, clear opportunities exist to advance the ethical conduct of research through our activities.

6. Process • We will develop and refine increasingly specific recommendations with feedback from SACHRP and input from key stakeholder groups. • SIIIDR will incorporate information from the September 2007 Request for Information which sought public comment on matters of concern to the subcommittee. • We will engage and seek comment from academic and professional organizations, IRB professionals, and patient advocacy groups.

7. Framework for SIIIDR activities How do we define (and how do IRBs, Investigators Identify) the “special population” requiring protection? How do we decide who may provide consent for those who are unable to consent for themselves? How do we define “reasonable risk” when ability to consider consent is limited or absent?

8. Structure • Three working groups (Populations, Approval Criteria, LAR) • Weekly meeting of co-chairs • Monthly subcommittee teleconference • Two-day meeting in early 2008

9. Working Group Membership Populations LAR R/B & Approval Criteria Paul Appelbaum, Jeffrey Botkin, Anne Donahue, Laurie Flynn, David Forster, Edgar Kenton Lisa Leiden, John Luce, John Oldham, Laura Roberts, Gustavo Roman, David Strauss

10. From the SIIIDR Charge The Subcommittee will develop either one or both of the following products: (1) recommendations on the interpretation of …Subpart A provisions that will enhance protections for this population; and (2) recommendations for a new subpart under 45CFR part 46 that would provide additional regulatory protections for this population.

12. “Population” Working Group • First efforts will limit consideration to impairment arising from disorders which affect decision-making. • Capacity and its impairment are task specific. • Impairment in capacity refers specifically to the capacity to make a particular research decision. • Such impairment can occur in wide range of conditions. • Some form of evaluation of capacity should be required in all cases of consent. • Assessment of capacity, like consent itself, requires an ongoing process. • Efforts to enhance autonomy should be a central consideration.

13. R&B/Approval Criteria Working Group • With appropriate protections, the inclusion of individuals who are unable to consent for themselves is essential as it will permit access to novel and investigational treatments and advance understanding, diagnosis, prevention, and treatment of conditions which impair decision-making. • Practical and clinically meaningful approaches to risk/benefit assessment are of paramount importance in order to protect individuals and promote necessary medical progress.

14. Question How can SACHRP most effectively “advise, consult and make recommendations” in order to “improve functions within the authority of HHS” on the specific matter of the “legally authorized representative”?

15. Legally Authorized Representative §46.102 Definitions: (c) Legally authorized representative means an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedure(s) involved in the research.

16. State and Institutional Rules Do not address or inconsistently address: • Research-specific rules, • Who may provide consent for those who are unable, • Scope of covered research activities, • Definition and identification of populations who are unable to consent, • Reasonable or acceptable risk when proxy or surrogate consent is permitted.

17. LAR and the Regulatory “Dead End” • Subpart A requires the “legally effective informed consent” of the research subject. • For those who cannot consent for themselves, Subpart A permits consent by a “legally authorized representative (LAR)” to the “procedures used in the research.” • But, the federal regulations do not define LAR. This is left to “applicable” local (State) law. • The States, with rare exceptions, have not defined LAR for research.

18. How Can SIIIDR/SACHRP address the LAR problem? • Is a consistent national approach required? Is it possible? • Is there a role for OHRP guidance in this area? • Is there a role for federal regulations in this area? • How can SIIIDR/SACHRP advise or otherwise promote the development of model state legislation?

19. Enhancing Protections For Individuals With Impaired Decision-making 1. Ethics: principles and conceptual framework 2. Federal regulations 3. Federal regulatory interpretation and guidance 4. State Law ? 5. Institutional policies and procedures 6. IRB function and requirements 7. Investigator responsibilities 9. Subject/participant 8. Research staff 10. The LAR