1. ETHICS OF CONSENTING IMPAIRED INDIVIDUALS THERAPEUTICS Col Xolani Currie, Nat Dipl Rad, BA, HED, MPH Regulatory Oversight Manager Project Phidisa

2. INTRODUCTION Historically the reputation of clinical research has been tarnished by the performance of studies on individuals without their informed consent. Advanced HIV/AIDS disease may lead to mental disorders, which may compromise a person’s decision making capabilities. Under these circumstances, it may be difficult for a person to give informed consent for research studies such as Project Phidisa. There are National and International regulations governing the informed consent process where the patient’s mental capabilities have been compromised by injury or disease.

3. DEFINITION OF TERMS Mentally Incompetent Patients: These are individuals with mental disabilities, which include psychiatric, cognitive or developmental disorders, regardless of the cause. Mental illness: Is defined by the Mental Health Act as any disorder or disability of the mind, and includes any mental disease, any arrested or incomplete development of the mind and any psychopathic disorder. Legally Authorized Representative:This is an individual, 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.

4. INTERNATIONAL AND NATIONAL GUIDELINES Declaration of Helsinki For a research subject who is legally incompetent, physically or mentally incapable of giving consent or is a legally incompetent minor, the investigator must obtain informed consent from the legally authorized representative in accordance with applicable law.

5. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) NIH, National Bioethics Advisory Commission (NBAC), Maryland, New York, Canadian Tri- Council and Council of Europe Core Safeguards: Institutional Risk-Benefit Assessment. Consent Assessment. Necessity Requirement. Proxy Decision Maker and Sufficient Evidence of Patient’s Remaining Preferences and Interests. Respect for Patient Assent and Dissent. Independent Monitors.

6. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) Institutional Risk-Benefit Assessment. Potential Direct Benefit - Fewer safeguards. Potential Benefit Justifies Risks. Risk- Benefit Profile as Favourable as Available Alternatives. Only Council of Europe Guidelines Prohibit Research with no Direct Benefit and Poses Greater than Minimal Risks.

7. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) Consent Assessment Canadian Tri-Council and Council of Europe Consider Persons to be Competent to Consent Barring Evidence to the Contrary. Assess the Understanding of all Participants. Enhance Participants’ Understanding. Give Formal Assessment.

8. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) Necessity Requirement Except for NIH, the other Guidelines agree that those unable to consent should be enrolled only when Investigators cannot obtain the desired information by enrolling those who can consent. Those unable to Consent may be enrolled only when the research concerns the condition responsible for their incapacity.

9. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) Proxy Decision Maker and Sufficient Evidence of Patient’s Remaining Preferences and Interests Those who lost ability to consent should participate in research only when it is consistent with their remaining preferences and interests. Research with no Direct Benefit requires positive evidence. Proxies should make decisions based on substituted judgment and best interests standards.

10. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) Respect for Patient Assent and Dissent Participants who express sustained dissent should be withdrawn. Explain Research Plan and obtain assent of those capable of providing it.

11. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) Independent Monitors Consent Monitors provide independent assurance that there is sufficient evidence that enrolment is consistent with participant’s remaining preferences and interests. Consent Monitor act as a witnesses to the consent process.

12. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) The SA Good Clinical Practice Guidelines The following guidelines must be followed when conducting research in people with cognitive disabilities: The research must be relevant/scientifically sound. Provide sufficient justification for involving people with mental disabilities who are institutionalised as the study population. Ensure appropriate evaluation procedures for ascertaining participants’ ability to give informed consent.

13. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) The SA Good Clinical Practice Guidelines (Cont…) If participants are deemed unable to understand and to make a choice, then an appropriate individual, able to consent on their behalf must be sought. Ensure that consent is free from coercion and risk to patients. Ensure that no more than minimal risk is involved, or if minimal risk is involved, the risk is outweighed by the anticipated benefits of the study for the participants and the importance of the knowledge, which will emanate from the research.

14. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) The Medical Research Council of South Africa Research should never be carried out in mentally handicapped patients, which could equally well be undertaken in adults who are not mentally handicapped. Research in mentally handicapped patients should be limited to that which is related to mental handicap.

15. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) The Medical Research Council of South Africa (Cont..) Many mentally handicapped patients are able to give consent. Often additional time, patience and the assistance of friends and helpers may be required to ensure that conditions of voluntariness and understanding are fulfilled. It should be appreciated that vulnerability to exploitation and suggestibility are common features of the mentally handicapped, although this may not be superficially obvious.

16. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) The Medical Research Council of South Africa (Cont..) If the procedure is of a therapeutic nature, i.e. may be of direct benefit to the patient himself, consent may be given by a representative in accordance with the provisions of section 60A of the Mental Health Act 18 of 1973. In terms of that section, consent to medical treatment of, or operations on, mental patients may be given by specified persons.

17. INTERNATIONAL AND NATIONAL GUIDELINES (Cont..) Section 60A of the Mental Health Act 18 of 1973 The following priority list is set up: The curator appointed by the court to the person or property of the patient. The patient's spouse. A parent. A major child. A brother. A sister. The persons enumerated have precedence in that order.

18. QUESTIONS