1. Research with Vulnerable Populations Marisue Cody, PhD, RN IRB Chair Training Washington DC, April 9, 2004

2. Objectives  Criteria for permissible research  Levels of risk justified  Capacity assessment  Surrogate decision-making and consent

3. Subject vulnerability “when some or all of the subjects are likely to be vulnerable to coercion or undue influence,…additional safeguards must be included in the study to protect the rights and welfare of these subjects.” 45 CFR 46.111(b)

4. Diminished autonomy  Mental capacity—ability to understand and process information  Voluntariness—freedom from the control or influence of others

5. Examples of vulnerable subjects  Children, prisoners, pregnant women  Handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons  Students, employees, members of the armed forces  Patients with incurable diseases, persons in nursing homes, patients in emergency situations

6. What are they vulnerable to?  Physical control  Coercion  Undue influence  Manipulation

7. Impaired decision-making capacity VHA Handbook 1200.5 Appendix D

8. If subjects with psychiatric disorders, dementia, and other mental impairments were excluded from studies, persons with these conditions would be deprived of the improved health care research can produce. Dresser R. Mentally disabled research subjects: The enduring policy issues. JAMA 1996; 276: 67-72.

9. When can research be done?  They comprise the only appropriate study population  The research question focuses on an issue unique to subjects in this population

10. Degree of risk  Minimal risk  “Minor over minimal”  Acceptable risk-knowledge ratio  “Maximal potential risk”

11. Acceptable risk?  Initial trials of a new drug for AD: 63% stops the progress of the disease ~50% it even produces some restoration of cognitive capacity 20% -- no effect. 15% serious and, in two cases, a fatal reaction.  Is this level of risk acceptable? Post SG, Full-spectrum proxy consent for research participation when persons with Alzheimer Disease lose decisional capacities: Research ethics and common good. Alzheimer Disease and Associated Disorders 2003; 17: S3-S11.

12. Limiting risks  Inclusion/exclusion criteria  “Aggressive monitoring” Routine and constant Respect for subjects’ physical resistance or other expressed dissent When to halt…..

13. Capacity to consent  Presumed competent to consent unless there is evidence of serious mental disability  Provide a plan for determining the incapacity

14. Competence vs. capacity  “Competence” -- legal and moral status of individuals that entitles them to make their own decisions  “Capacity” – cognitive, affective, and volitional abilities that underlie competence

15. Formal procedures for capacity assessment  Goes against the presumption of assumed competence in adults  Reserve for populations with high probability of decisional-impairment  Who decides? Structured questionnaire Clinical care model: leave the decision to a disinterested 3 rd party

16. Surrogate consent  When prospective patient is incompetent or has impaired decision-making capacity Practitioner, in consultation with the chief of service, or COS, after an appropriate medical exam Consultation with psychiatrist or licensed psychologist if based on a diagnosis of mental illness Consent disclosures to the surrogate Explanation to subject

17. Legally authorized representative  Court appointed guardian, only with the court’s consent  Health care agent appointed in a durable power of attorney  Next of kin (1200.5 pg. 20) : Spouse, Adult child, Parent, Adult sibling, Grandparent, or Adult grandchild (depending on state law)

18. What to tell representative…  Description of the proposed research and the risks and benefits of participation  Their obligation as the patient’s representative, i.e., try to determine what the patient would do if competent or, what they think is the subjects’ best interests

19. Where do we go from here?