1. Ethics and Policy Conference Day One Summary

2. Goals of the Meeting Educate people about the status of various protocol decisions Define areas where we can reach consensus Continue to discuss other areas and decide how to address in the future Future: draft paper on key ethical issues

3. Ethical Issues in the Selection of Subjects Efficacy vs. effectiveness Competing goals of inclusion and study result Risk to OR team (if transplant is “standard” therapy, then need to assume risk, if “experimental” this may not be required)

4. Are Subject Selection Criteria Fair? Hepatitis C –Accelerated HIV, liver failure with co-infection –High percentage of Hep C population had no fibrosis –Increased risks post transplant: may be putting them at greater risk –Consider limits of data –Need to consider reimbursement implications

5. Are Subject Selection Criteria Fair? Viral Load Criteria for Liver –A valid marker of disease progression, transmission, and survival. Benefits even with low but detectable levels (without immunosuppression). –Risk to OR staff – unacceptable to some –Some interest in broad VL inclusion criteria (current protocol builds in flexibility)  Working group

6. Are Subject Selection Criteria Fair? People with Clotting Disorders –Controllable –Inclusion makes sense History of Opportunistic Infections –Exclusion until 20 patients – re-valuate (approx 6 months from now) –Evidence of immune reconstruction –Discussion ongoing

7. Policy and Ethics - Donors Cadaveric vs. Living Donors –Scarcity: increasing demand –Cadaveric donation currently done –Families cannot dictate where organs go –Living donors: willingness to participate does not mean informed consent –Many living donors do not understand potentially limited benefits – or personal risks

8. Policy and Ethics - Donors Should recipients be required to reveal HIV status? –Informed consent of donor vs. privacy of recipient –Legal issues in some states –HIV a “loaded” disease –Requirement at one center Inform donor of use in research study? State regulations on direct donation Dangers in giving choice to donors Need for a standard/policy in our study (in the future)

9. Policy and Ethics - Donors High Risk Donors –How do we define high risk? (e.g. age) –Choice: high risk donor vs. death –Choice: HIV + donor vs. death (not for this study) –MD concerns: “do no harm” and lawsuits –High risk organs could undermine study outcome: “compassionate and wrong” –Rejection at organ procurement level

10. Role of Community Advisory Boards UCSF CAB with national membership Consider CAB at each site (UCSF CAB to “buddy” local CABs?) Can use ACTG CAB at most sites Can be involved in: inclusion criteria, informed consent, reimbursement advocacy, social support. CAB needs to learn transplant issues and surgeons need to learn how HIV treatment has changed In it for the same reasons: participants and study

11. Reimbursement CMS (HCFA): no explicit exclusion Need published data: minimum survival targets Region-level decisions: “when the rules are silent, local Medicare intermediaries have authority” Creative strategies for reimbursement Not “systemic” disease if no OIs Call Cheryl!  Working Group

12. Protecting Subjects to Minimize Risks and Maximize Benefits of Participation Off study protocol would do harm: deplete the pool of organs and delay study Risk of incomplete/inaccurate data Public awareness of bad outcomes off study Transplants to PWHIV are happening now: should not stop & should capture data How easy to collect basic data? (IRB?) How often re-evaluate inclusion criteria?

13. Outreach and Advocacy Do outreach! But…will sites be overwhelmed? Need systems to handle public inquiries: –Printed materials –Web sites postings Each site should consider a CAB Importance of public perception