1. Ethical Challenges in Conducting Research with Adolescent Girls John S Santelli, MD, MPH, FAAP, FSAHM Professor, Pediatrics and Population and Family Health Chair, Heilbrunn Department of Population and Family Health Girls and HIV AIDS2016 satellite session Durban, South Africa July 21, 2016

2. Three Key Points • Research with adolescent girls is needed • Ethical research with adolescent girls is possible, despite cultural and institutional barriers/blinders • You need to be ethically proactive • Educate yourself • Educate your research ethics committee/institutional review board (IRB)

3. Need for Research on Adolescent Girls and HIV Infection • High rates of infection among adolescent girls, soon after sexual initiation • Potential for primary prevention • Inadequate understanding of HIV risk • Behavior factors • Power dynamics and inequalities • Limited set of efficacious interventions to prevent HIV infection among adolescents • We need to know more

4. Barriers to Research with Adolescents • Adult discomfort with adolescents • Adult discomfort with sexuality • Research ethics committee members are adults! • Adolescents as “children” • Research regulatory system more focused on protection than inclusion • “Protection to their death” • Confusion about adolescent ability to provide informed consent • Limited adolescent expertise on ethics committees

5. Research Ethics with Adolescents in Developing Countries • Belmont principles • Development considerations • Inclusion and protection • Emerging capacity to provide informed consent • Waiver of parental permission

6. Belmont Principles and Adolescents

7. Adolescents, Research, and the Convention on the Rights of the Child (CRC) • Adolescents as rights holders • CRC principles: • Best interests of the child • Evolving capacity of children • CRC supports adolescent participation and autonomous decision-making, and access to health and health care consistent with these principles

8. Legal Capacity to Provide Informed Consent in Research • Adults - presumed to be competent • Children - presumed to be incompetent • Adolescents?

9. Development of executive functions: Higher level reasoning skills and logic Ability to self-regulate emotions and responses Changes in the pre-frontal cortex Adolescent risk-taking: Adolescents differ in risk perceptions Hot and cold cognition Adolescents make reasonable/rationale decisions in cold cognitive states Neuroscience Perspectives on Cognition and Risk Taking (Steinberg 2008, Millstein, 2002; Gerrard, 1996; Halpern-Felsher, 2001)

10. Research Decision-Making Capacity Capacity = the ability to appreciate the risks and benefits of clinical situation and to make reasoned choices Children (<9 years) - Capable of a basic understanding Early Adolescents (9-13 years) - Understand risk/benefits; less able to consider multiple conflicting points; decisions similar to adults Mid to late adolescents (14+ years) - Similar to adults Weithorn, 1982

11. National laws, UN treaties, state laws Age of majority Age to consent for health care Emancipated minors (motherhood, marriage, military) Minor consent Specific medical conditions (sexally transmitted infections, pregnancy, drug use) Mature minors A need to harmonize informed consent requirements for treatment and research Adolescent Legal Status related to Medical Care and Research

12. Parental Permission • Form of surrogate decision-making • Ethical assumptions: • Parents will usually make decisions in the best interests of their adolescent • Issues arise when… • There is a conflict of interest between the parent and adolescent • Parental permission introduces additional risks to the adolescent • Parental permission is a barrier to the research, or biases the data such that it is not accurate

13. 45 CFR 46 Subpart D Adequate provisions for soliciting assent of child Adequate provisions for soliciting permission of parent(s) Local IRBs may waive parental permission under 46.408(c) “not reasonable requirement” 46.116(d) waiver of informed consent Federal Regulations and Adolescents: Assent and Permission

14. Guidelines for Adolescent Health Research(Society for Adolescent Health and Medicine) • Consistent with the ethical principles in Belmont • Respect for • Parents as the essential protectors of their children • Emerging capacity and autonomy of the adolescent • Promote an interpretation consistent with federal regulations • Ways to waive parental permission

15. Conclusions • Research with adolescent girls is possible • Ethical research with adolescents needs to be grounded in a nuanced understanding of: • Ethical principles, legal status, and national regulations • Evolving capacity of the adolescent • Connectedness of adolescents to family and community • The importance of both inclusion and protection