1. 1 GROUPWORK (1) Legal Regulatory Group Rotational brainstorming problem analysis Consultation on ethical-legal complexities in adolescent HIV vaccine & microbicide trials: Durban, South Africa 5 September 2007

2. 2 1. What are the key issues? Legal: Overarching themes: -Balance between protection, autonomy, scientific progress, human rights, and public health considerations -Transparency of the law Communicating/disseminating legal requirements to communities, researchers, and participants?

3. 3 1. What are the key issues? (i)Consent –Consent was identified as a critical legal issue that required further attention. Key problems included: The lack of clarity in many legal systems re: who consents –What to do regarding children without parents (e.g., with legal guardians, wards of the state, in child-headed households)? Different degrees of protection for different children –Who qualifies as a legal guardian? -What steps should a researcher take to verify guardianship or parental status? -In clinical trials, caregivers cannot provide consent –Requirements re: emancipated or mature minors –Lack of sufficient exceptions to parental consent »E.g., MSM – worry about involving parents – modification of laws to accommodate these sorts of exceptions so at risk populations will still be able to access research options

4. 4 1. What are the key issues? Legal (ii) Privacy Key problems included: -Mandatory reporting of statutory rape/abuse If adolescents are engaged in behavior that they don’t want to reveal to their parents, must weigh right to privacy against laws requiring reporting Although the best interests standard can be used to consider how to weigh privacy against competing interests, it may be complex to apply across different groups Privacy (con.) -Disclosure of HIV status Obligations on health care workers to disclose information if an HIV+ person has one or more sexual partners? –Healthcare workers may have a duty to encourage, counsel and facilitate disclosure with the participants’ permission, but not be solely responsible for advising partners directly - criminal law implications –If exposing others to HIV is/becomes a criminal offense, how will this affect health care workers with knowledge of a patient’s HIV status? How will this be balanced against medical privacy laws?

5. 5 What are the key issues? (i) Consent (con.) The age of consent for sexual activity may not correlate with social realities Obtaining true understanding for informed consent from adolescents may be complex as procedures need to be adapted for their needs –Will need a tool assess understanding Difference between assent and consent is not always fully understood

6. 6 1. What are the key issues? Legal (con.) (iii) Equity concerns when conducting multinational research in the context of variation in laws within and between countries Legal frameworks generally Definitions of adolescents Age of marriage/majority/medical treatment/consent to sexual activity Approvable risks/benefits

7. 7 1. What are the key issues? Regulatory: –Timing of trials: ambiguous guidance that adolescents can be enrolled in trials at phase IIb or phase III –Licensing and approval What data is required in adolescents? Conflicts between requirements in developing and developed countries –May delay development of the drug –Drug companies may decide not to license drugs in developing countries if they can’t do so in developed countries –Regulatory process: Disputes about regulatory framework between various legal bodies—courts, ethics committees/IRBs, administrative agencies

8. 8 1. What are the key issues? Regulatory (con.): –Communication between different regulators –What are the roles of the various regulators? –To what extent are frameworks appropriate for scientific developments? Prevention research does not fit neatly into the regulatory framework in the U.S. –Payment to trial participants (overlap with ethics) In South Africa, local v. national standard for compensation amounts Reimbursements – equal value for adolescents and adults? Need to look at value and mechanisms.

9. 9 2. Is anything unique to, or plays out differently in, vaccine vs microbicide trials? Microbicide trials must enroll participants who are sexually active, therefore may be greater legal complexities when they involve younger participants Disagree – think that both need to be sexually active Collection of data re: sexual behavior is necessary for microbicide trials, but not necessarily for vaccine trials Disagree – might change with new generations of microbicides which are not coitally dependant

10. Adapted from E Emanuel (2005)10 3. Are any issues unique to, or exacerbated in, developing vs developed country setting? Differential reporting requirements and/or enforcement of reporting requirements Less possibility of laws being enforced in the South Variations regarding age of consent/mature minors/emancipated minors likely vary as much within countries as between them Differential access to health care services may generate different obligations on the part of researchers Need for capacity-building in the developing world –Currently, there are fewer formal, legally-binding processes in the developing world for consultation with regulatory bodies (e.g., pre-IND consultation with the U.S. FDA)

11. Adapted from E Emanuel (2005)11 3. Are any issues unique to, or exacerbated in, developing vs developed country setting? Licensure requirements may be more stringent in developed countries with lower disease burden Social/cultural practices –May focus on family more in developing countries, which may affect the enforcement of reporting requirements –Views of autonomy in adolescents, including legal requirements re: emancipated or mature minors

12. 12 4. What are the priorities we should focus on? Age of consent/assent Who consents for children with no legal guardian? –Who can consent for adolescents in general? Regulatory requirements for conduct and approval of research in adolescents –Risks/benefits –Compensation/Payment Is this an ethical or legal issue? Is the term “compensation” appropriate?

13. 13 4. What are the priorities we should focus on? Timing of research with adolescents Legal obligations of researchers –Confidentiality/Disclosure – key priority –A comprehensive IC will /should detail what info will and will not be shared with the parent post- enrolment –Use of Certificate of Confidentiality – limitations inherent but is a useful mechanism in the US and with clinical trial staff in SA