1. International Research Ethics Jenell Coleman, M.D. Clinical Fellow, Reproductive Infectious Diseases, UCSF M.P.H. Candidate 2005, UCB March 1, 2005

2. My Experience Ethical sensitivity Lack of adequate training in ethics International research –Unethical foundation Goal –Stimulate further ethical review of your own projects

3. Definition Ethics: ways of examining the moral life –Normative: formulation and defense of a system of fundamental moral principles and rules that determine which actions are right and which are wrong What people ought to do –Non-normative: factual investigation of moral behavior and beliefs How people reason and act Beauchamp and Childress. Principles of Biomedical Ethics. 1989

4. General Terms Action Rule Principle Theory

5. Ethical Principles Autonomy –Respect for persons; self-governance –Free choice without coercion; informed consent Justice –Equal distribution of risks and benefits –Persons from groups unlikely to be among the beneficiaries of subsequent application should not be involved in research Beneficence –Minimize risks and maximize benefits Nonmaleficence –Do no harm

6. Ethical Theories Utilitarian –Greatest good for the greatest number –Some people may have to carry the burden which will ultimately benefit society –Social benefits of research for future pts. Deontological –Human rights based –Individual rights

7. Informed Consent Disclosure of information Understanding of this information Voluntariness Competence Consent

8. Incompetence Inability to evidence a choice or preference Inability to understand one’s situation Inability to understand disclosed information Inability to give a reason Inability to give a rational reason Inability to give risk/benefit-related reasons Inability to reach a reasonable decision Appelbaum and Roth. Archives of General Psychiatry. 1982; Roth and Meisel. Emory Law Journal. 1982

9. Vulnerable populations People infected with HIV Women Children People with drug addictions Poor individuals Elderly Prisoners Military recruits

10. Exploitation Subjects participating in the research project are burdened with the risks of the project, yet are not recipients of the benefits –May even be doing harm –Violation of nonmaleficence principle

11. Ethical Guidelines Post WWII –Nuremburg Code –Declaration of Helsinki –Belmont Report

12. Declaration of Helsinki World Medical Association 1962 In any medical study, every patient- including those of the control group- should be assured the best proven diagnostic and therapeutic method

13. DHHS Ethical Guidelines It is permissible to observe the standards of the host country, if it was determined that they “ afford protections that are at least equivalent to those provided in this policy”

14. International Ethical Guidelines 1993...the ethical standards applied should be no less exacting than they would be for research in the sponsoring country itself

15. Placebo Trials 1994ACTG 076 Results »$800-$1000 1994WHO Recommendations 199515 RCTs and 1 equivalency trial 1997Public Citizen letter to DHHS 1998CDC funded trial results

16. Placebo Arguments Pro –beneficence –standard of care –scientific rigor –equipoise Anti –beneficence –autonomy –nonmaleficence –exploitation –violation of international ethical guidelines

17. Colonialism Cultural Relativism Imperialism -isms

18. Colonialism The state of developing countries is the byproduct of colonialism –Reason why substandard care is provided –Reason for the widespread poverty –Reason for the dependence on 1 st world countries for financial assistance

19. Cultural Relativism Cannot apply our ethical standards and definitions to a different culture What are the ethical beliefs of the community?

20. Western Imperialism “These are Ugandan studies, conducted by Ugandan investigators, on Ugandans, for the good of their people” The extension or imposition of power, authority, or influence –Sweden RCT –South African viewpoint –Ethical Review Boards

21. Placebo Arguments Pro –beneficence –standard of care –scientific rigor –equipoise Anti –beneficence –autonomy –nonmaleficence –exploitation –violation of international ethical guidelines

22. Discussion How do you define standard of care? Are placebo controlled trials in low income countries unethical? Are developing countries exploited? What do researchers owe the subjects, if anything?

23. Responsibility of researchers Disconnect between research and policy Passive role of many researchers Lack of support for subjects after study ends RESEARCH FINDINGS POLICY

24. Human Rights Clarify the true purpose of the research –Must matter to the subjects Evaluate likely effectiveness –Honest, rigorous investigation into the potential effectiveness in that population Determine whether the research is well targeted –Disproportionately impacting certain groups in society?

25. Human Rights Examine the research for possible human rights burdens –Balancing of potential benefits to the health of the community with the human rights repercussions Determine whether the research is the least intrusive that can achieve the objective If a coercive measure is truly necessary to avert a significant risk, guarantee fair procedures to persons affected Gostin and Mann

26. In sum, Researchers –aim to strengthen the community –know the purpose of the research –formulate a plan to implement study results

27. ... a placebo-controlled trial may be ethically acceptable, even if proven therapy is available, under the following circumstances: - Where for compelling and scientifically sound methodological reasons its use is necessary to determine the efficacy or safety of a prophylactic, diagnostic or therapeutic method; or - Where a prophylactic, diagnostic or therapeutic method is being investigated for a minor condition and the patients who receive placebo will not be subject to any additional risk of serious or irreversible harm. Declaration of Helsinki Revision 2002

28. “ The health of my patient will be my first consideration.” -Declaration of Geneva of the World Medical Association