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

1. Subcommittee on the Inclusion of Individuals with Impaired Decision-making in Research Presentation of Preamble and Recommendations 4-10 for Approval Presented to SACHRP March 4, 209 David H. Strauss, M.D. SIIIDR Co-chair

2. 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.

3. From SIIIDR’s 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.

4. Preamble • Disorders and conditions in which impaired consent capacity occur are common, and cause morbidity and mortality on a large scale. There is a pressing need for research. • The fundamental protections provided by consent are not available. Consent by an LAR is not equivalent. • The oversight community has progressed, but has it been properly equipped to oversee research with subjects who are the most vulnerable to exploitation and highly susceptible to research-related harm? • The current framework of regulations and guidance is all but silent with regard to research with subjects who cannot consent. • For example, how is the population defined, what are the safeguards required, what is reasonable risk, who may consent on behalf of those who cannot?

5. Preamble • We examined current practice, the empirical literature, and sought expert consultation (scientists, regulators, advocates). Our membership reflected expertise and a diversity of perspective. • We answered our charge in the affirmative: new guidance and/or regulations are necessary to provide appropriate research protections for individuals who have impaired consent capacity • We offer recommendations 4-10 for your approval.

6. Preamble • We support guidance over regulation: guidance offers a rich, flexible format for educating the field and influencing practice on a meaningful time frame. • We believe a single comprehensive resource document of guidance will best serve the field. • We attempted to avoid being overly proscriptive—we recognize the considerable expertise of the IRB community and the extent to which the academic community feels over-regulated. • We remained committed to our primary purpose--to the enhance research protections for individuals who are not able to protect themselves through the process of consent.

7. SIIIDRMembership Paul Appelbaum, Jeffrey Botkin*, Anne Donahue, Laurie Flynn, David Forster*, John Luce, John Oldham, Gustavo Roman, David Strauss* Edgar Kenton, Laura Roberts, Samuel Tilden, Lisa Leiden

8. For example: Recommendation 3d. In making the determination as to methods to be used to ascertain consent capacity, it is important to note that more intensive approaches involve burdens for participants and researchers alike. Therefore, these should be reserved for those situations in which impairment is more likely to be present, anticipated benefits are fewer, and foreseeable risks are greater.

9. Recommendation 1,2,3 • Defines the term “consent capacity” • Provides information on the complex nature of consent capacity as it relates to IRB and investigator responsibilities. • Guides the field on approaches to the identification of affected participants and to need for capacity assessment.

10. Recommendation 4 • Outlines IRB review requirements for research which proposed to include subjects with impaired consent capacity. • Calls for special IRB membership and reviewer qualifications • Details factors to be considered in the process of subject selection—when is it appropriate to call upon subjects with impaired consent capacity to take part in research?

11. Recommendation 5 • Provides conceptual and practical framework for risk-benefit considerations. • Guides the careful analysis of several continuous variables including risk assessment, r/b in relation to standard care, unique direct benefit, and the relationship between LAR and subject. • Discusses the idea of approval thresholds that are tailored to the study population • Calls for upper limits of risk to be defined, limited.

12. Recommendation 6 • Emphasizes the value of self-determination by the research participant. • Requires involvement of the participant in decision-making, where possible • Requires assent and definition of dissent

13. Recommendation 7 • Defines initial and ongoing roles, responsibilities and expectations for the LAR • Defines investigator responsibilities with regard to the LAR

14. Recommendation 8 • Seeks further information on the interpretation of applicable law

15. Recommendation 9 • Defines a hierarchy of individuals who may provide consent on behalf of individuals who lack consent capacity when LAR is not otherwise defined.

16. Recommendation 10 • Asks DHHS to explore opportunities to promote the development and adoption by the states of uniform rules to define LAR.