ETHICAL AND LEGAL ISSUES WITH HUMAN SUBJECTS AND COMMUNITY WORKERS

1. ETHICAL AND LEGAL ISSUES WITH HUMAN SUBJECTS AND COMMUNITY WORKERS Sana Loue, J.D., Ph.D., M.P.H., M.S.S.A. Partners for Health: Communities and Researchers Working Together Loma Linda University March 11, 2010

2. ADVISORY • This training is not intended to be legal advice and does not provide legal advice with respect to any individual or situation. Individuals are advised to consult with their legal representative for any individualized legal advice. • Legal and ethical obligations may be consistent or may differ.

3. ROADMAP • Setting priorities • Privacy and confidentiality • Defining terms • Consequences of breach • Legal limits of confidentiality • Mechanisms to protect confidentiality • Issues to consider • Randomization procedures • Defining randomization • International and US perspectives • Working with multiple boards • ECs/IRBs, DSMBs, SABs, CABs • Differing perspectives • Strategies to resolve conflicts • Considering conflicts of interest • Ethical and legal issues

4. SETTING PRIORITIES • Priorities may differ between researchers and community. • Differences may be attributable to • Funding issues • Personal impact • Statistical data • Differing sensitivities • Demands of daily living • Strategies to resolve differences?

5. PRIVACY AND CONFIDENTIALITY • Defining the terms • Consequences of breach • HIPAA • Legal limitations on confidentiality • Procedures to maximize confidentiality • Issues to consider in CBPR

6. PRIVACY • Defined as the condition of being free from unauthorized observation or intrusion • Anonymous means that someone cannot be identified at all. • Confidential means that, although the person can be identified, their privacy and confidentiality are maintained to the extent possible • Safeguards to privacy • Closed offices • Sound proof areas

7. CONFIDENTIALITY • Refers to unauthorized disclosure of information relating to the individual • Distinguished from privileged communication, which refers to the legal right of a client to not have their communication disclosed in legal proceedings • applies to only certain types of communications with specified individuals in specified circumstances

8. POTENTIAL CONSEQUENCES OF BREACH OF PRIVACY OR CONFIDENTIALITY • Legal implications • Insurance (life, health, disability) • Housing • Employment • Law enforcement implications • Interpersonal implications • Potential loss of relationships • Distancing • Labeling and secondary labeling • Psychological/emotional implications • Diminished self-esteem and self-worth • Felt/internalized stigma

9. HIPAA • Health Insurance Portability and Accountability Act of 1996 (HIPAA) • Includes the standards for an individual’s privacy rights, to enable them to understand and control how their health information is used

10. LEGAL LMITATIONS ON CONFIDENTIALITY • Mandatory reporting requirements • Enumerated communicable diseases • Child abuse and neglect • Elder abuse and neglect • Partner violence (some states) • Duty to warn if there is imminent harm to self or identifiable other and the individual has the means to carry this out (Tarasoff v. Regents of the University of California, adopted in variety of forms by many states) • Audits by funding agency or institutional review board • Professional review

11. MECHANISMS TO PROTECT CONFIDENTIALITY • Computer passwords • Locked cabinets • Locked offices • Locked briefcases • Location of files • Location of discussions • Messages • Mailings • Certificate of confidentiality • Procedures for data sharing

12. CERTIFICATES OF CONFIDENTIALITY • Available from appropriate institute of NIH • Insulates data from most legal proceedings/issues • Information available at http://grants2.nih.gov/grants/policy/coc/appl_extramural.htm

13. CONFIDENTIALITY AND PRIVACY ISSUES FOR CONSIDERATION IN CBPR • Participatory action research: To what extent can/should the investigator be involved in the activity that he or she is observing? Legal/ethical issues? • In conducting “shadowing,” must the research team member identify him- or herself to all present as a researcher? Implications of disclosure? Nondisclosure? • To what extent should researcher be able to collect information about a third party without that individual’s informed consent?

14. RANDOMIZATION PROCEDURES • Defining randomization • International documents

15. DEFINING RANDOMIZATION • Every individual has an equal probability of being assigned to any of the arms or treatments in the study • Procedure must be established before people are enrolled into study • Allows different arms of study to be as similar as possible

16. INTERNATIONAL DOCUMENTS • Helsinki Declaration • 32. The benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention, except in the following circumstances: • The use of placebo, or no treatment, is acceptable in studies where no current proven intervention exists; or • Where for compelling and scientifically sound methodological reasons the use of placebo is necessary to determine the efficacy or safety of an intervention and the patients who receive placebo or no treatment will not be subject to any risk of serious or irreversible harm. Extreme care must be taken to avoid abuse of this option. • 33. At the conclusion of the study, patients entered into the study are entitled to be informed about the outcome of the study and to share any benefits that result from it, for example, access to interventions identified as beneficial in the study or to other appropriate care or benefits. • Council of International Organizations of Medical Sciences (CIOMS) • Randomization preferred method for assigning individuals to study arms • when there is no established effective intervention; • when withholding an established effective intervention would expose subjects to, at most, temporary discomfort or delay in relief of symptoms; • when use of an established effective intervention as comparator would not yield scientifically reliable results and use of placebo would not add any risk of serious or irreversible harm to the subjects.

17. WORKING WITH MULTIPLE BOARDS • Institutional review boards/ ethical review committees • Community advisory boards • Scientific advisory boards • Data safety monitoring boards

18. POTENTIAL DIFFERENCES IN PERSPECTIVES BETWEEN COMMUNITY ANDDIVERSE BOARDS • Perceptions of risks and benefits • Views of risk-benefit balance • Procedures to be utilized for recruitment and enrollment • Need for written informed consent • Availability of waiver of consent • Acceptability of comparison in randomized trial • Emphasis placed on dissemination of findings

19. Ethical Review Committees: Purpose • The primary purpose of ethics review committees should be “to contribute to safeguarding the dignity, rights, safety, and wellbeing of all actual or potential research participants.” (The World Health Organization, Operational Guidelines for Ethics Committees That Review Biomedical Research, 2000, p. 1) • WHO Guidelines: review committees are to consider the principle of justice, which requires the equitable distribution of the burdens and benefits of research among all groups and classes in society.

20. ETHICAL REVIEW COMMITTEES:Composition • The WHO Guidelines recommend that the review committee reflect diversity in expertise, age, gender, and community concerns. • It has also been suggested that ethics review committees reviewing HIV-related protocols include HIV health consumers among its members(National Health and Medical Research Council, 2005). • Members of the review committee are to be free from bias and conflicts of interest. In this context, the WHO Guidelines define “conflict of interest” as arising • When a member (or members) of the EC holds interests with respect to specific applications for review that may jeopardize his/her (their) ability to provide a free and independent evaluation of the research focused on the protection of the research participants. Conflicts of interest may arise when an EC member has financial, material, institutional, or social ties to the research (World Health Organization, 2000: 21).

21. ETHICAL REVIEW COMMITTEES: Functioning • The scope of the EC’s review is quite broad and encompasses • the scientific design and conduct of the study, • the recruitment process, • the provisions developed to ensure the protection of the research participants, • the procedures to protect the confidentiality of the data, • the informed consent process and • community considerations.

22. ETHICAL REVIEW COMMITTEES:Review: Protection of Participants • Suitability of investigator’s qualifications to conduct study • Plans to withhold/withdraw standard therapies for research and justification to do so • Provisions for medical care for participants during and following research study • Adequacy of medical supervision and psychosocial support for participants • Steps to be taken if participants voluntarily withdraw from study • Criteria for extended use, emergency use, compassionate use of study products • Arrangements and procedures for communication of study-related information to participant’s physician • Description of plans to make research product available to participants following close of study • Description of financial costs to participants • Rewards and compensation to be provided to participants • Provisions for compensation and/or treatment for participants in the event of injury, disability, or death attributable to participation in research

23. ETHICAL REVIEW COMMITTEES:Review: Protection of Confidentiality • Description of persons having access to data • Measures to be taken to ensure confidentiality and security of information

24. ETHICAL REVIEW COMMITTEES:Review: Informed Consent Process • Description of the process • Identification of individuals responsible for obtaining consent • Adequacy, completeness, and understandability of the written document • Justification for intent to include as participants individuals who cannot provide their own consent • Assurances that individuals will receive information during the course of participation that is relevant to their participation • Provisions for responding to participant questions and complaints during the course of the study

25. ETHICAL REVIEW COMMITTEES:Review: Community Considerations • The impact on and relevance to the community of the research, e.g. stigma • Mechanisms and extent of dissemination of findings to the community

26. U.S. FEDERAL REGULATIONS AND INSTITUTIONAL REVIEW BOARDS • At least 5 persons with specific skills • Ensure that risks of the research outweighed by the anticipated benefits • Ensure that the rights and welfare of research participants are protected • Ensure that informed consent will be obtained by adequate and appropriate means

27. DATA SAFETY MONITORING BOARDS • DSMBs were developed in order to monitor • on an ongoing basis the data collected during • the course of a study (Gordon, Sugarman, and Kass, 1998). • In order to provide adequate monitoring, the DSMB must include experts in all of the disciplines needed to ensure participant safety including, if relevant to the study, clinical trials experts, biostatisticians, bioethicists, and clinicians who are knowledgeable about the disease and the treatment or intervention that are the focus of the study. • The DSMB generally meets in an open session with the investigators and subsequently in a closed session during which the members review the emerging data.

28. DSMB RESPONSIBILITIES • Evaluate the progress of the trial, including data quality, recruitment, accrual and retention, participant risks and benefits, performance at the various trial sites, and scientific or therapeutic developments that could affect the participants’ safety or the study’s ethicality; • Make recommendations to the investigators, the IRB, and/or the institution regarding the need to continue with or terminate one or more arms of the study, or the entire study; and • Protect the confidentiality of the data and the results of the monitoring.

29. TYPICAL SITUATIONS CONFRONTING DSMB: Phase III Clinical Trial • A phase III trial is often designed to compare a new treatment to a standard treatment or, now more rarely, to no treatment (placebo). Participants may be randomized to a particular arm (experimental treatment, standard treatment, or placebo) and the data may be masked. • These studies usually involve a large number of participants who are followed for longer periods of treatment exposure. There may be long term effects resulting from longer exposure to the study agent or there may be significant safety or efficacy differences between the control and study groups for a masked study. • A DSMB may perform monitoring functions to regularly assess the trial and offer recommendations concerning its continuation.

30. SABs: Formation • Usually developed specifically for a particular study or center • Invited by the principal investigator or center director • Size determined by needs of center or investigator • Comprised of individuals with varying expertise, e.g. ethics, biostatistics, disease, behavior, study methodology

31. SABs: Functions • To assist in developing future trajectory for research efforts • To provide information about possible funding opportunities • To provide feedback about current research and methodological approach • May meet face-to-face, teleconferencing, videoconferencing • Meetings often annual or semiannual, but may be more frequent

32. COMMUNITY ADVISORY BOARDS • Community advisory boards have often been employed in the context of community-based participatory research, also known as community-centered research(Cox et al., 1998; Israel et al., 1998).This approach assumes that research is to be conducted as a partnership between the researchers and the community, with active community input and engagement in all aspects of the research process(Melton et al., 1988).

33. MODELS OF CABs IN HIV RESEARCH • The “broad community” model • Frequently observed in Thailand and Zimbabwe • Takes a long-term view of its role, focusing its attention on such issues as sustainability, independence in funding and accountability, and the promotion of community-initiated research (Morin, Maiorana, Koester, Sheon, and Richards, 2003). • Membership consists of individuals from a broad spectrum of the community, including religious and political leaders, educators, and representatives from nongovernmental organizations (nonprofit organizations). • The “population-specific” model • Concerned with a specific research protocol and with the needs of specific groups at increased risk of HIV infection in the context of that protocol, such as injection drug users. • Representatives on such CABs are often drawn from the population/community participating in the research (Morin, Maiorana, Koester, Sheon, and Richards, 2003). • CABs of both models exist at the local and national levels.

34. CABs and HIV TRIALS • CABs have been developed in conjunction with both clinical trials for the treatment of HIV in infected persons and with HIV prevention trials. • CABs developed for clinical trials have frequently included HIV-infected persons. • CABs focusing on the prevention of transmission to uninfected individuals often reflect the interests of various communities that may be at increased risk for HIV infection (Morin, Maiorana, Koester, Sheon, and Richards, 2003).

35. CABs: Functions • Provide guidance in the development of the informed consent process, the design of research protocols, and the design of recruitment and enrollment procedures; • Serve as a bridge between research participants and the research team (Loue and Mendez, 2005; Morin, Maiorana, Koester, Sheon, and Richards, 2003; Strauss et al., 2001). • Confront and discuss ethical issues in the context of these roles, including the provision of care and treatment to those screened for trial participation, the protection of vulnerable populations, and the value of the proposed research to the host community (Morin, Maiorana, Koester, Sheon, and Richards, 2003).

36. CABS: Barriers to Recruitment and Retention of Members • Differences in • Language • educational and literacy levels • experience in the larger community • Difficulties identifying representatives form the community (Siskind, 2004) • The use of technical terms by researchers • Limitations of time and funds for child care and travel (Silver et al., 1996) • Increasing severity of illness member.

37. CAB MEMBER MOTIVATIONS • The existence of a mission statement has been associated with better attendance and more active participation of CAB members (Chovnick, 2005; Cox et al., 1998). • Individual motivations for participation on a CAB include • a commitment to fighting HIV/AIDS • a sense of legitimacy • the opportunity to contribute something meaningful to the community • material rewards such as reimbursements, lunches, and stipends (Morin, Maiorana, Koester, Sheon, and Richards, 2003). These material rewards have, however, been somewhat controversial. Researchers have reported that the provision of such benefits to CAB members in a rural area of western Kenya prompted concerns regarding the objectivity of the CAB members because the rewards were provided in the context of a high local level of unemployment and poverty (Odhiambo et al., 2004).

38. ETHICAL ISSUES IN FORMING A CAB • The selection of community representative: who has the right to speak for a “community” • Conflicts resulting from the multiple roles of providers as advisory board members, research interviewees, and providers to study participants • Conflicting priorities of community members and researchers (Loue and Mendez, 2005).

39. SELECTING A COMMUNITY REPRESENTATIVE • How is community defined? • Is the individual selected in touch with that community? • If out of touch, individual may not be attuned to the sensitivities of prospective participants so that, inadvertently, prospective participants could be harmed by a lack of attention to their concerns. • Overemphasis on the community’s sensitivities could result in the termination of the research, thereby depriving individuals of not only the burdens of the research, but its benefits as well. • In both instances, the principle of respect for persons is violated because individuals are either not adequately protected from harm, or are not afforded an opportunity to decide for themselves whether or not to participate. • In the latter instance, the principle of justice, which seeks an equitable distribution of the benefits and burdens of research, may also be violated.

40. MULTIPLE ROLES OF CAB MEMBERS • Some of the CAB members may have professional relationships with individual who are participants in particular studies that are the focus of the CAB’s attention. Ethical issues may arise where the CAB member wishes to access for their use in a clinical context data collected from a particular participant in the research context. • Various strategies can be utilized to reduce the likelihood of such requests and/or to address such requests when they are made. • All CAB members can be advised at the commencement of their participation that no disclosures of research data will be made, other than in the aggregate. • Participants can be given the option to have specific information conveyed by the research team to named providers with a signed, written request/release of information from the participant.

41. DIFFERING PERSPECTIVES ACROSS BOARDS AND COMMUNITIES • Perceptions of risks and benefits • Giving back to the community • Availability of information • “Hard” referrals to community resources • Involuntary termination of individual’s participation in study • Whether arm or entire study should be terminated • Views of risk-benefit balance • Often IRB emphasis on physical harm, overemphasis by researchers and IRB on benefits • Procedures to be utilized for recruitment and enrollment

42. DIFFERING PERSPECTIVES ACROSS BOARDS AND COMMUNITIES • Written informed consent • Problematic depending on history of participants • Readability level and language of consent forms • Availability of waiver of consent • Particular issue in research with children • Acceptability of comparison in randomized trial • Placebo v. “standard” treatment • Difficulty defining standard care • If true equipoise, unclear whether experimental condition will produce harm or benefit • Emphasis placed on dissemination of findings

43. STRATEGIES TO RESOLVE CONFLICTS • Only IRB has legal authority • Ability of PI to negotiate between boards • IRB practices • Community participation • Reliance on cultural expert

44. GUARDING AGAINST ETHICAL AND LEGAL PROBLEMS • Develop comprehensive study protocol to address various situations • Situations requiring informed consent • Procedures for disclosure of information • Procedures for notification/reporting • HIV test results • Child or elder abuse or neglect • Partner violence • Immediate threat to self or others • Procedures for disclosure and resolution of conflict of interest • Procedures for reporting, investigations, and resolution of sexual harassment issues • Develop guidelines for non-IRB boards interacting with study: CAB, SAB, DSMB • Roles and responsibilities of board members • Parameters for access to study data and participant identity