1. Surrogate ConsentAssessing Capacity Paul S. Appelbaum, MD Dollard Professor of Psychiatry, Medicine & Law Columbia University

2. Why Surrogate Consent? Some areas of research will be difficult or impossible to pursue without the participation of subjects who are unable to provide consent Categories include: Children (separate regs, not discussed here) Adults with impaired capacity

3. Alzheimers Disease As Paradigm for Surrogate Consent By 2040, roughly 80 million people worldwide will suffer from ADmajor public health issue Impaired decision making appears early in the course of the illness, even in mild AD Research on diagnosis and treatment will often involve persons unable to give consent

4. Who Will Give Consent for Persons with Impaired Capacity? Federal regulations provide mechanism for surrogate consent, allowing consent by legally authorized representative (LAR): 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.

5. Who Can Be An LAR? 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). Some states have statutes, regulations, or common law that specifically address consent by someone other than the subject for participation in research. Most states have no law specifically addressing the issue of consent in the research context. In these states, law that addresses who is authorized to give consent on behalf of another person to specific medical procedures or generally to medical treatment may be relevant if the research involves those medical procedures or medical treatment. OHRP FAQs on Informed Consent

6. Possibilities for Designation of An LAR: 3 Options Designation in advance of becoming decisionally impaired, i.e., via an advance directive designating a surrogate Only a small proportion of the population has advance directives Unclear whether ordinary advance directives provide authority for research decisions though OHRP language suggests that they do

7. Second Option for LAR Designation after becoming decisionally impaired, i.e., via default designation in that jurisdiction Statutory designation via hierarchy Common law reliance on familial decision making But has downside of taking decision out of subjects hands Or…

8. Third Option for LAR When approached for research participation Possible when subject has lost capacity to make research decision, but retains capacity to appoint a surrogate or proxy decision maker Respects autonomy interest of subject by empowering him/her to designate surrogate Thus, when possible, may be preferable approach, i.e., concurrent directive

9. When Is Someone Capable of Appointing a Surrogate? If criteria require that subject fully grasp the decision that the surrogate will make, not much point in having a surrogate Perhaps the key lies in the subject grasping the function of the surrogate and the potential consequences of the designation, and trusting the surrogate with the decision

10. Leeway: How much freedom or leeway would you give [a] close family member to go against your preference and instead [enroll/not enroll] you in the study? (n=1,456) None Some Complete 41.4 39.3 19.3 33.2 40.6 26.2 45.2 37.9 16.9 39.6 39.2 21.1 LP Drug RCT Vaccine GeneRx Views of Older Americans (age 51+), n=1400+ (Kim et al, Neurology 2009) Many People Trust Family Members to Make Research Participation Decisions Even Against Their Preferences Among those willing to participate in research based on decision by a surrogate, 76% would allow some or complete leeway.

11. How To Decide On Specific Criteria for Capacity to Appoint a Proxy? Gradual development with attention to process Establish provisional criteria Test in the field Remain open to revisions based on experience/results Study that follows conducted by Scott Kim (UMich) and colleagues (Arch. Gen. Psychiatry, Feb. 2011) 11

12. Goal To determine to what extent a person with dementia who lacks the capacity to consent to a research study might have the capacity to delegate the responsibility for a consent decision by appointing a research proxy

13. Methods of Study - 1 Subjects recruited from 3 AD clinics with possible or probable AD, stratified by MMSE Two MacCAT-CRs to assess capacity to consent to research for 2 different studies: Randomized clinical trial testing a new medication for AD Randomized placebo-controlled (sham surgery) neurosurgical clinical trial of cell transplantation for AD

14. Methods of Study - 2 Also receive instrument to assess capacity to appoint a proxy (CAPA) All interviews done in subjects homes over 2 visits and videotaped 5 experienced clinicians (C/L psychiatrists who regularly do competence assessments) were trained to review tapes and make categorical determinations of capacity on CAPA and MacCAT-CRs

15. Approach to Assessment of Capacity to Appoint a Research Proxy Approach In the absence of consensus criteria, use of inclusive criteria, based on MacCAT-CR Nature of research (3) Nature of research proxy (5) Pros and cons of having a proxy (2) Performance-related elements (4) Disclosure precedes questions Semi-structured, 14 items, score 0-28.

16. Items in Capacity to Appoint a Proxy Assessment (CAPA)

17. Copyright restrictions may apply. Kim, S. Y. H. et al. Arch Gen Psychiatry 2011;68:214-219.

18. 18 Distribution of MMSE scores (0-30)

19. Distribution of CAPA Scores (0-28) 19

20. Copyright restrictions may apply. Kim, S. Y. H. et al. Arch Gen Psychiatry 2011;68:214-219.

21. Copyright restrictions may apply. Kim, S. Y. H. et al. Arch Gen Psychiatry 2011;68:214-219.

22. Conclusions from Study - 1 Capacity to appoint a research proxy better preserved than the capacity to consent for a drug RCT, which was better preserved than the capacity to consent to a higher-risk neurosurgical RCT Experts appear to apply a sliding-scale to competence determinations based on complexity and risk

23. Conclusions from Study - 2 Valid informed consent for research requires subjects to learn new, technical information about research design, a particularly difficult task for persons with AD. Appointing a proxy, requires trusting someone else to make a decision, a familiar, relationship-based concept. Subjects will have had a close relationship for years with most proxies.

24. Conclusions from Study - 3 Most important of all, there is a window in AD during which subjects are incapable of consenting to research, but capable of appointing a proxy 38% of those incapable of consenting to the drug RCT and 55% of those incapable of IC for neurosurgical RCT still have capacity to appoint a research proxy 91.7% of those with MMSE 24 or higher were capable of appointing a research proxy

25. Future of Surrogate Consent For disorders with partial retention of decision making capacity (i.e., AD but not coma), option of asking subjects to appoint surrogate appears viable Further development of consensus on criteria will be helpful