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1. www.icad-cisd.com New Prevention Technologies Workshop Module 6: Ethics

2. HUMAN RIGHTS AND ETHICAL CHALLENGES IN NPT RESEARCH

3. OUTLINE Overview of research ethics: origins, guidelines, principles Overview of role of various players in biomedical prevention research Community engagement: models, challenges, vulnerability and targeted populations Dynamics of North-South research Case study: Cambodia, Cameroon, Thai trials Standard of prevention and care for trial participants Use of ARVs for prevention vs treatment

4. What is “Ethics”? • Ethicsis a way of understanding and examining what is “right” and what is “wrong” • Bioethicsis a way of understanding and examining what is “right” and what is “wrong” in biomedical research and practice.

5. Activity What is your understanding of these words ? Respect Harm Fairness

6. Principles of Research Ethics • Respect for Persons • Beneficence/Non-Maleficence • Justice/Non-Exploitation

7. Respect for Persons Autonomy • Says that each individual: • Is unique and free; • Has the right and capacity to decide; • Has value and dignity; and • Has the right to informed consent. Protection for vulnerable persons • Special protections must be in place for those whose decision–making capacity is impaired or diminished, whether due to physical or social factors

8. Beneficence/Non-Maleficence • Protection of the study participants is the most important responsibility of the researcher • Researchers must: • Protect the physical, mental and social well-being of each research participant; • Minimizes physical and social risks; • Maximize the possible benefits; and • Retain the community perspective.

9. Beneficence/Non-Maleficence • ON BALANCE: • The research should generate more good than harm; and • Risks of research should be reasonable in light of the expected benefits to the individual and to society.

10. Justice/Non-Exploitation • The principle that calls for fairness in the conduct of research is the principle of justice/non-exploitation • Research must: • Ensure a fair distribution of risks and benefits • Research should not be done in a community that is not likely to benefit from the result • Conduct equitable recruitment of research participants; and • Provide special protection for vulnerable groups.

11. RISKS and BENEFITS What are the potential RISKS of becoming involved in a prevention trial? For participants? For communities? DISCUSSION QUESTIONS What are the potential BENEFITS of becoming involved in a prevention trial? • For participants? • For communities?

12. Participant Risks vs. Benefits RISKS BENEFITS • Biologic/Physical • Social/Emotional • From the product: side effects • From HIV/STI testing • Partner issues • Stigma • Improved access to health care • Better prevention • Risk reduction counseling • STD treatment • Condoms • Other • Cash • Sense of social contribution

13. Participants Have Said the Benefits of Participating in MicrobicideTrials Include: • Access to medical services and regular health checks is considered the biggest benefit • Counseling about women’s bodies, sexuality, reproductive tract infections, STIs, and HIV • Good relationships with study staff • Feeling empowered; improved communication with male partners and children • Access to study gel; improved sex due to gel • Contributing to a women’s health cause: “One is helped but is also helping others”

14. Participants Have Said the Risks and Burdens of Microbicide Trials Include: • HIV testing considered biggest burden • Discomfort during pelvic exam • Long waiting times at clinic • Feeling of loss at end of study • Worries about side effects

15. Community Burdens and Benefits • Risks and Burdens • Possible stigma • Diversion of local health personnel • Benefits • Improved health infrastructure • Training • Community education on HIV/research • Preferential access to product if it proves effective

16. Will participating in trials increase people’s risk of HIV? • Generally, no... • People will become infected during the trial but not because of the trial • People in both arms should have lower HIV prevalence than people in the general community Condoms only Condom only ` Risk Condoms + placebo gel Condoms + microbicide (if it works) Before trial During Trial

17. Important Ethics Concepts

18. Equipoise Equipoise is a state of genuine uncertainty or doubt about whether one intervention or treatment is superior to another Equipoise is a necessary condition for clinical research to be morally acceptable If the scientific community “knows” that one treatment is better than another, it would be considered unethical to withhold it Questions remain, however, about how to decide when “scientific or clinical consensus” exists about the relative merits of different treatments

19. Therapeutic Misconception “Therapeutic misconception” refers to the tendency of some research participants to wrongly assume that whatever drug or intervention they are offered must work or be beneficial (or why would it be offered?) It occurs when the goals of research and those of therapy or “health care” become confused in the participants mind. The therapeutic misconception is a major threat to “informed consent.”

20. Voluntary Informed Consent Voluntary informed consent is the agreement given by a well-informed person who: Has received the necessary information expressed in spoken words and in writing; Has adequately understood the information; and Has made the choice to participate (or not participate) without coercion.

21. Essential Elements for Informed Consent • Research description (what is being studied, what is the procedure, who is sponsoring the study?); • Risks of participating; • Benefits of participating; • Alternatives to participation, such as other studies or services in the area; • Assurance that information will be kept confidential; • Compensation for time, travel or possible harm; • Contacts (whom to contact with questions/concerns); and • Voluntary participation and withdrawal.

22. Informed Consent, Cont’d • Adequate understanding includes the difference between research and health care • related concept: “therapeutic misconception” • After thinking seriously about the information, the person can arrive at a decision without being forced, threatened or offered something so valuable that free choice is impossible • related concepts: “coercion” and “undue inducement”

23. Legal and moral agenda can sometimes conflict Indemnify the research institution VERSUS Facilitate collaborative decision making Length of forms Degree of technical information imparted Written versus oral consent Emphasis on right to withdraw

24. Informed Consent is a Process • Informed consent is a process of collaborative communication and decision making, not the signing of a form • Informed consent requires that prospective participants: • Be appropriately informed about the nature of the research • Adequately understand this information and its implications • Voluntarily decide to participate, without coercion • Explicitly consent to participate, orally or in writing

25. Activity Discussion questions: What are good ways to convey this kind of information to people to ensure that if they agree to participate in a study, they are giving informed consent? How do you know if people have understood the information and are making a free choice to participate?

26. Balancing respect for culture and respect for persons • concept of “individual autonomy” may be in conflict with entrenched cultural norms or expectations • example: may be expected that a woman’s husband has the right and authority to make decisions regarding her health care • While recognizing local value and ethical pluralisms, ethics is also concerned with universal principles of conduct

27. Case Study – Informed Consent A microbicide study is taking place in an African country. Focus groups in the community have shown that many women are interested in a microbicide because they are not able to negotiate condom use with their partners. Many women are coming to the study clinic to enroll in the trial. A community advisory group is formed with community leaders and representatives. A male member of the group says that he does not approve of the study because the women are not required to get the consent of their partners to enroll. A local women’s group expresses concern that a woman who enrolls in the trial without telling their partner risks being harmed if her partner finds out she is participating.

28. ACTIVITY In some settings it is generally expected that a woman’s husband has the right and authority to make decisions regarding her health care In this instance, how should one balance respect for persons with respect for culture? Should sexual partners be involved? Are there creative strategies for encouraging partner engagement? What might you recommend as an appropriate way to respect both of these values in this instance?

29. Overview of Role of Various Players

30. Who? Ethical Research

31. Who Decides? • Decisions have to be made about what the acceptable balance is between risks and benefits • CABs and ethics committees can help judge acceptability of risk:benefit ratio overall • The informed consent process helps an individual make his/her own judgment about the risks and benefits • The health and well-being of the participant can never be sacrificed for “research’s sake” or the “greater global good”

32. Who are the Players in HIV NPT Research? • Academic researchers and universities • Community members and organizations, community advisory boards • Private sector – pharmaceutical and biotech companies • Government funders and regulators • Health care providers

33. Academic Researchers Basic Researchers • lead the scientific discovery and development of NPT candidate concepts and products Clinical Researchers • lead the clinical testing of candidate NPT products, testing efficacy as well as issues of acceptance and accessibility • establish and maintain the highest standards of ethical conduct of clinical trials Social Researchers • conduct research on acceptability, preparedness, access and delivery issues • work alongside clinical research to understand usability and acceptance of NPTs

34. Community Roles • develop community acceptance and preparedness for NPTs • anticipate and mitigate stigma associated with trial • raise awareness about the role community based organizations can play before, during and after trials • facilitate clinical trial recruitment • incorporate NPTs into prevention education and training programs for specific vulnerable populations • develop strategies for promoting and distributing NPTs once available • advocate for investment in NPT research and development

35. Private Sector • invest in research and development, manufacturing and production • technical innovation • establish clinical infrastructure (e.g., epidemiological laboratories, trials infrastructure) during the pre-clinical development of the NPT that will be needed in clinical research • translational research: generate data, clinical materials

36. Public Funding is Essential Global Annual Microbicides R&D Investment 2009 in USD$ millions Source: HIV Vaccines and Microbicides Resource Tracking Working Group Why aren’t large pharmaceutical companies investing? • Perceived low profitability • Liability concerns • Lack of in-house expertise • Uncertain regulatory environment

37. Government Funders and Regulators • provide funding for NPT research programs, academic researchers, conferences • coordinate domestic and global efforts • ensure that adequate clinical research facilities exist • ensure availability of properly trained staff • help build public awareness and support for research and development • achieve speedy and appropriate access once a NPT becomes available

38. Health Care Providers • Monitoring, prevention and control of HIV/AIDS and STIs • Help with NPT delivery, education and access • With ARV-based NPTs, may need to be prescribers

39. Community engagement

40. What Do We Mean by Community?

41. Competing & Changing Definitions of Community • “…separate and overlapping groups of people who are infected and affected by HIV in various ways” Good Participatory Practice, UNAIDS/AVAC • “ …trial participants, their families and partners, other local stakeholders, and service providers/community groups within the geographic parameters of the clinical trial location. MDS Civil Society Working Group Report • “…the group of people who will participate in or are likely to be affected by or have an influence on the conduct of the research.” HIV Prevention Trials Network, Community Program FAQs

42. …Or No Definition At All In addition to many competing definitions, often times people talk about “community” without defining what they mean or who they are specifically referring to

43. Locating Community • When we talk about community, it is important to frame the discussion in terms of: • Who is included in the particular “community” we are discussing? • And distinguish which “level” we are referring to

45. “Trial Participants & Study Staff” refers to the individuals directly participating in the trial, in some instances their partner(s), and study staff working at the trial site.

46. “Host Community” refers tothe individuals living in the area of the trial, their leaders, and community-based organizations that serve or represent them directly. This can also include traditional healers, local radio, and other community structures (including CABs)

47. “National Stakeholders” describes anyone who has a role to play in the political, scientific, and social enterprise of microbicide development in the larger, national community. It includes political decision-makers, MoH, regulatory bodies, ethical review committees, national NGOs, donors, national media, etc.

48. “International Civil Society” refers to non-profit, organized, citizen-led movements or groups interested in the goals, process, and outcomes of microbicide research, and/or in the rights of communities or research participants. Civil society includes international or regional NGOs (GCM/UNAIDS), international or media.

49. Issues of Power Power imbalances exist across multiple lines: Principal investigators versus field staff, Northern researchers versus Southern; community versus research enterprise; within communities and CABs One goal of community involvement and NPT advocacy is to work towards reduced power disparities Pretending that power imbalances do not exist, however, breeds the worst form of tokenism

50. Why do we need Community Involvement? Ethical principle of beneficence Maximize benefitsand minimizes risks for participants and for host communities. Minimize exposure to controversyand risk of disruption Increase the transparency and accountability of the research to the community Improve quality of trials, participant retention, adherence and accurate self-reporting: ensuring trial procedures are acceptable to participants and other decision-makers Strengthen local capacity and infrastructure