1. © 2008 Wiggin and Dana Studies Involving Individuals with Impaired Capacity: Assessing Capacity to Consent Michelle Wilcox DeBarge, Esq. Wiggin and Dana LLP mdebarge@wiggin.com Combined HSPO/IRB Committee Meeting September 10, 2008

2. © 2008 Wiggin and Dana 2 Goals of Informed Consent Ensure understanding of the risks, benefits (or lack thereof), alternatives Satisfy ethical principles (e.g., respect for persons) Comply with the law Manage legal risk Manage business/reputational risk (preserve public trust)

3. © 2008 Wiggin and Dana 3 Ethical Principles The Belmont Report Respect for Persons incorporates two ethical convictions: 1.Treat individuals as autonomous agents 2.Protect persons with diminished autonomy

4. © 2008 Wiggin and Dana 4 Ethical Principles The Belmont Report Informed Consent: Respect for persons requires giving individuals the opportunity to decide what will or won’t happen to them. The informed consent process contains three elements: information, comprehension, voluntariness. Where capacity is lacking or diminished, comprehension (and thus true voluntariness) may be absent. In such cases, respect for persons demands seeking permission from others in order to protect the individual from harm.

5. © 2008 Wiggin and Dana 5 Federal Law Impaired Consent Capacity “No investigator may involve a human being as a subject in research... unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative.” 45 CFR 46.116, 21 CFR 50.20

6. © 2008 Wiggin and Dana 6 Complicated Underlying Issues: 1.Who can serve as the legally authorized representative (“LAR”)? 2.What level of impaired capacity warrants obtaining informed consent from the LAR, and how can the involvement of the prospective subject be maximized? 3.What are the criteria for assessing impairment, and when should the assessment occur? 4.What are the standards or guidelines to which the LAR must adhere in providing informed consent? 5.What are the threshold risk-benefit criteria for the IRB to approve enrollment of subjects with impaired capacity?

7. © 2008 Wiggin and Dana 7 “Legally Effective Informed Consent” Q: What should be considered in seeking informed consent from individuals with diminished decision- making capacity? A: The HHS regulations are silent on the consent procedures specific to subjects with impaired decision-making capacity, for example, as a result of trauma, mental retardation, some forms of mental illness, or dementia, whether temporary, progressive or permanent. - HHS OHRP Q and A, available at: http://www.hhs.gov/ohrp/informconsfaq.html

8. © 2008 Wiggin and Dana 8 “Legally Authorized Representative” Q: Who can be an LAR for the purpose of providing consent on behalf of a prospective subject? A: The issue as to who can be an LAR is determined by the laws of the jurisdiction in which the research is conducted (e.g., local or state law). - HHS OHRP Q and A, available at: http://www.hhs.gov/ohrp/informconsfaq.html

9. © 2008 Wiggin and Dana 9 OHRP Position: LAR must: be explicitly recognized in a state statute or regulation as having authority to provide substituted consent to participate in research; OR be formally vested with such authority by the prospective participant or a judicial authority.

10. © 2008 Wiggin and Dana 10 HELP IS ON THE WAY???

11. © 2008 Wiggin and Dana 11 HHS Office of Human Research Protections (OHRP) Secretary’s Advisory Committee on Human Research Protections (SACHRP) Subcommittee on the Inclusion of Individuals with Impaired Decision-making in Research (SIIIDR)

12. © 2008 Wiggin and Dana 12 SIIIDR’s Charge: Develop recommendations for consideration by SACHRP about whether guidance and/or additional regulations are needed for research involving individuals with impaired decision-making capacity. Develop either one or both of the following, depending on its conclusions: –(1) recommendations on the interpretation of specific subpart A provisions that will enhance protections for this population; and –(2) recommendations for a new subpart under 45 CFR part 46 (and FDA’s human subject regulations) that would provide additional regulatory protections for this population.

13. © 2008 Wiggin and Dana 13 July 30, 2007: SIIIDR presentation to SACHRP additional guidance or regulation is necessary covering (1) assessing ability to consent; (2) the definition of legally authorized representative; and (3) IRB risk criteria September 5, 2007: OHRP notice in the Federal Register seeking public comment: due 12/4/07 about whether guidance or additional regulations are needed October 29 2007: SIIIDR presentation to SACHRP divided into 3 working groups still unsure whether there should be regulations or guidance December 6, 2007: OHRP extension of public comment period to 1/14/08 March 2008: SIIIDR Presentation to SACHRP three recommendations approved July 2008: SIIIDR presentation to SACHRP regulations regarding legally authorized representative discussed

14. © 2008 Wiggin and Dana 14 SIIIDR Recommendations Approved by SACHRP March 2008 Meeting

15. © 2008 Wiggin and Dana 15 SIIIDR: Recommendation #1 “Guidance should adopt the term ‘consent capacity’ (following the working document developed by NIH) to denote the specific abilities necessary for a prospective research participant to understand and use information relevant to consent.” *NIH, “Research Involving Individuals with Questionable Capacity to Consent: Points to Consider,” March 11, 1999, available at http://www.grants.nih.gov/grants/policy/questionablecapacity.htm. http://www.grants.nih.gov/grants/policy/questionablecapacity.htm

16. © 2008 Wiggin and Dana 16 SIIIDR: Recommendation #2 “Guidance should provide information for institutions, IRBs, and investigators on the nature of consent capacity and its impairment as it relates to research participation.” Capacity occurs along a continuum and may fluctuate over time Impaired capacity should not be limited to consideration of specific disorders Consent capacity is task-specific; depends on the nature and complexity of the decision-making

17. © 2008 Wiggin and Dana 17 SIIIDR: Recommendation #3 “Guidance should address the implementation of appropriate safeguards related to the identification of individuals who may have impaired consent capacity. Such safeguards can be applied prior to participant enrollment, and as appropriate, throughout the course of research participation.” Anticipated vs. unanticipated impaired consent capacity Methods to assess capacity Qualifications of those assessing capacity Requirements for re-assessment and re-consent

18. © 2008 Wiggin and Dana 18 SIIIDR: July 2008 Recommendations to SACHRP “in draft” Recommendation VII “ [SIIIDR] recommends that HHS develop a Subpart to 45 CFR 46 to include new regulations related to the inclusion of adults who lack consent capacity.”

19. © 2008 Wiggin and Dana 19 SIIIDR: July 2008 Recommendation VII to SACHRP (cont.) 1.When an IRB approves the conduct of research under Subpart A and determines that it is appropriate for consent to research to be obtained from the legally authorized representatives of adult subjects who lack decisional capacity to consent on their own behalves: a. Such determination must be made at a convened meeting of the IRB and not by means of expedited review, unless the research qualifies for waiver of consent. An initial determination must be made by the convened IRB. Subsequent review and approval would follow guidance on continuing review; b.Where applicable law exists to determine who is authorized to serve as an LAR to consent to a subject’s participation in research, consent may be obtained only from an LAR in accordance with such law.

20. © 2008 Wiggin and Dana 20 SIIIDR: July 2008 Recommendation VII to SACHRP (cont.) c.In the absence of applicable law, one of the persons listed below, in the following descending order of priority, shall be considered the subject’s LAR and may consent to participation on behalf of the subject: (i) A person designated by the subject, while retaining the decisional capacity to do so, to make decisions for him/her regarding participation in research; (ii) A person by the subject, while retaining the decisional capacity to do so, to make decisions for him/her regarding non-research health care decisions; (iii) The subject’s legal guardian with authority to make health care decisions for the subject; (iv) The spouse, or if recognized by applicable law, the civil union partner or domestic partner of the subject; (v) An adult son or daughter of the subject; (vi) A parent of the subject; (vii) An adult brother or sister of the subject; (viii) An adult who has exhibited special care and concern for the subject.

21. © 2008 Wiggin and Dana 21 d. LAR consent on behalf of the subject shall be in accordance with applicable law. In the absence of applicable law, the decision shall be based on the known wishes of the subject (substituted judgment). If the LAR can not determine the subjects wishes, the decisions shall be made based on the best medical, psychological and other interests of the subject. SIIIDR: July 2008 Recommendation VII to SACHRP (cont.)

22. © 2008 Wiggin and Dana 22 In the Meantime... Principles to Consider Concerning Capacity Assessment 1.If no capacity, no legally effective informed consent. 2.Be sensitive to current restrictive OHRP position and UCHC policy and how it may affect assessment determinations. Be vigilant to ensure the integrity of the assessment process and capacity determinations. 3.Maintain flexibility: There is no one standard assessment “formula” for all studies or for all prospective participants in a study. (SIIIDR notes that no scale, instrument, or other assessment method has emerged as the standard in the field.)

23. © 2008 Wiggin and Dana 23 Principles to Consider Concerning Capacity Assessment (continued) 4.Ensure appropriate expertise on the IRB to address vulnerable population of individuals with impaired capacity. 5.Give thought to who is doing the assessments. Appropriately qualified and trained? 6.Consider need for periodic reassessments and consents if capacity may be fluctuating. 7.In studies where capacity is expected to diminish over time, encourage process for participants to appoint a representative to make future research decisions. 8.Maximize involvement in consent and decision-making by participants with impaired capacity whenever possible.