1. Ethical issues in selection of research subjects Bernard Lo, M.D. July 28, 2001

2. Is it care rather than research?  Potentially life-saving intervention  Liver transplant is standard care in other clinical settings  Transplant may be available outside trial

3. Different selection priorities  In clinical care  Well-being of individual patient paramount  Priority to those in greatest medical urgency  In research  Benefits/risks uncertain  Generalizable knowledge also a goal  Priority to most appropriate to answer research question

4. What is the research question?  Proof of concept  Generalizability

5. Proof of concept  Is intervention efficacious in optimal circumstances?  Negative study is definitive  Positive study needs follow-up in broader population

6. Generalizability  Is intervention effective in ordinary practice?  Need larger sample size  Positive study is definitive  Negative study may be due to selection

7. Subject selection for different research questions  If proof of concept  Select those with best prognosis after Tx  Exclude those with poorer or uncertain prognosis  If generalizability  Select those representative of population

8. Risk to health care workers?  Persons with high viral titers whose liver disease precludes HAART  If no resistance, likely to respond to HAART after Tx

9. Risk to health care workers?  Needlesticks during operation  Risk to HCWs is greater if higher titer  Ethical obligation to provide standard care, even at risk to self, but not experimental care?

10. Characteristics of ethical dilemma  Strong arguments for different positions  Reasonable people may disagree

12. Should HIV+ persons be given a scarce resource? How should scarce organs be allocated? Bernard Lo, M.D. July 29, 2001

14. Reaction to Mickey Mantle “With each crack of the bat, Mickey Mantle allowed us to dream. For one moment forget about everything else.”

15. Reaction to Mickey Mantle “Had my sister been a start baseball player perhaps she would be alive today… Unfortunately, her only claim to fame was that she was a loving wife and mother.”

16. Reaction to Mickey Mantle “I have lost three relatives to liver failure … None were given the preferential treatment he received… My only hope is that he doesn’t take advantage of his brand-new liver and revert to his old ways.”

18. Principles of “fair” allocation  Those with greatest medical urgency  Those most likely to benefit  Exclude those unlikely to benefit

19. Those with greatest medical urgency  Rescue those in greatest need  Probability of death  Likelihood of good outcome after Tx

20. Those most likely to benefit  Help the greatest number of patients  Groups with similar outcomes should have similar priority  Need outcomes data  Arguments over data, not principle  May conflict with medical urgency

21. Exclude those unlikely to benefit  Medical  Too sick: sepsis, other organ failure  Too healthy: survive without Tx  Poor adherence  Active substance abuse  Poor social support  Possibility of bias

22. Principles of “fair” allocation  Those with greatest medical urgency  Those most likely to benefit  Exclude those unlikely to benefit  Those who waited longest  Exclude those who cannot pay  Those who are “unworthy”?

23. Favor those who are “worthy”?  Past contributions to society  Future contributions to society  Traditional social/cultural values

24. Exclude those who are “unworthy”?  Behaviors that lead to illness  Groups stigmatized or marginalized  Public willingness to donate organs  History of early renal dialysis