1. Introduction to the USC Human Subjects Protection Program Executive Director, Susan L. Rose Office for the Protection of Research Subjects (OPRS) USC

2. RCR refers to : 1.Research with Animals 2.Conflicts of Interest and Scientific Objectivity 3.Data Acquisition and Management 4.Mentoring and Professional Relationships 5.Collaboration in Research 6.Authorship 7.Publication 8.Peer Review 9.Misconduct in Research 10.Human Subjects Research

3. What is USC’s Human Subjects Protection Program (HSPP)? Protects the rights, welfare, and safety of research subjects and assures excellence for research programs across the university Writes policies, creates educational materials and assures institutional compliance with regulations Maintains USC AAHRPP accreditation Consists of VP for Research, OPRS, Health Sciences and University Park IRBs, Office of Compliance, researchers and staff

4. Office for the Protection of Research Subjects (OPRS)… Establishes Human Subjects Research (HSR) policies Leads the HSPP team Oversees UPC and HSC IRBs Creates educational materials to ensure compliance with regulations Maintains policies current with new regulations, changing ethics and best practices For more info, visit: www.oprs.usc.eduwww.oprs.usc.edu

5. Historical Background of Human Subjects Research

6. Ethical and Regulatory Basis for Human Subjects Research Protections Nuremberg Code (1949) o Scientifically valid research design with potential to produce fruitful results for good of society o Voluntary consent of human subjects Declaration of Helsinki (1964) o Guidance for medical doctors undertaking biomedical research with human subject o Risk to benefit ratio o Review of research by independent committees o Informed consent Belmont Report (1978) o Respect for Persons o Beneficence o Justice Common Rule (1991) o Rules by which HSR is conducted HIPAA (1996) o Protects confidentiality of Private Health Information (PHI)

7. What is Human Subjects Research? Research*: A systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Human subject*: Living individual(s) about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information. Benefit: A valued or desired outcome; an advantage. Risk: The probability of harm or injury (physical, psychological, social, or economic) occurring as a result of participation in a research study. Both the probability and magnitude of possible harm may vary from minimal to significant. Federal regulations define only "minimal risk.“ *as defined in 45 part 46 / policy on the protection of human subjects

8. What is Not Human Subjects Research (NHSR)? Not Human Subjects Research are studies that do not meet the federal definition of: 1.Human subjects and/or 2.Research Examples: Program evaluation Course-related activities Analysis of data/specimens from deceased Analysis of specimens from commercial source

9. What is the Belmont Report (1978*)? Basic Principles for Human Subjects Research: Respect for Person: Acknowledges freedom and dignity of Subjects and requires subjects to voluntarily consent to participate Beneficence: Maximize benefits and minimize harms associated with research and ensure risks are reasonably justified Justice: Equal distribution of risk/benefits among all, i.e. equitable selection, recruitment, and fair treatment of research subjects *The National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research

10. Are Human Subjects Still at Risk? Jesse Gelsinger (1999) Died in a gene therapy trial at UPenn. Researchers were later cited for violations of safety standards and informed consent requirements. Ellen Roche (2001) Died after inhaling hexamethonium during an asthma study at Johns Hopkins. She developed a cough and flu-like symptoms which led to organ failure. Nicole Wan (1996) Died shortly after research related bronchoscopy (an examination of the breathing tubes in the lung) at the University of Rochester at New York. NEED FOR AN ETHICS CODE

11. Research Ethics Violations

12. What is an Institutional Review Board(IRB)?  An oversight committee charged with reviewing research involving human subjects  Functions as a surrogate human subjects advocate  IRB members can be faculty, staff or students of the institution and local community members  Human Subjects Research must be approved by the IRB before research begins

14. Why Informed Consent? Autonomy is the ethical principle Enables subject to:  Understand the benefits/risks/procedures  Voluntarily decide  Ask questions Circumstances of consent  Provides adequate time to consider participation  Minimize the possibility of coercion  Minimize the possibility of undue influence

15. Elements of Informed Consent Research Statement, Purpose, Duration, Procedures Risks/Discomforts Benefits to subject/others Alternatives to Participation Confidentiality Compensation/Medical Treatment Contact Information Voluntary/Refusal/No Consequences *Additional info may be required by IRB

16. Types of Consents Parental Permission Child Assent (7-12 yrs old) Youth Assent (12-17 yrs old) Short form (language barrier) Waiver of documentation (if consent can be detrimental) Information/Fact Sheet

18. What is Privacy and Confidentiality? What is the difference between privacy and confidentiality? Privacy is about people and setting Having control over the extent, timing, and circumstances of sharing oneself with others. Privacy is an individual right. Confidentiality is about data Disclosed private information, given in a relationship of trust, will not be divulged to others in ways not originally agreed upon. It is the obligation of the researcher to keep collected private information from being shared with others.

19. Vulnerable Subjects Vulnerability can be situational and individual Pregnant Women/Fetuses* Comatose patients Prisoners* Cognitively impaired Children* Employees/Students Homeless Vulnerability is a power differential Vulnerable subjects MUST receive extra protections *Federally protected categories: 45 CFR 46 b,c,d

20. What Are Concerns in International Research?  Protections must equal protections required in the US  Local permission expected / ethics board approval  Must have consent and recruitment documents in language understandable by the subjects  Cultural Sensitivity expected of researcher *International research concepts also apply in domestically homogenous locales such as Koreatown

21. Institutional Review Board (IRB) Submissions greater than minimal risk; e.g. drug study/domestic violence study reviewed by a full committee Full Board minimal risk; e.g. blood draw / alcoholism IRB Chair/designee reviews Expedited (9 categories) not greater than minimal risk; e.g. blood pressure / educational tests IRB Chair /designee/staff reviews Exempt (6 categories) e.g. analyzing discarded tissue IRB Chair/designee/staff review Coded Data / Specimens doesn’t meet federal definition or is coded data IRB Chair/designee/staff reviews Not Human Subjects Research Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

22. What are Coded Data/Specimens? Research with Coded Date/Specimens requires IRB Review through a shorter form submission Existing private information/specimens not collected for the current research project where: The investigator(s) cannot ascertain the identity of the individual Data/specimens labeled with code or link Examples: Obtaining and analyzing discarded tissue Analyzing data set obtained from other institution OHRP Guidance on Coded Data / Specimens www.hhs.gov/ohrp/policy/cdebiol.html

23. What are IRB approval criteria?* Risks are minimized Reasonable Risk/Benefit Ratio Equitable Subject Selection Obtain / Document Consent Data Monitoring for Safety Privacy and Confidentiality Additional safeguards for vulnerable populations Other: Investigator Qualifications Scientific Merit Cultural Appropriateness Application Clarity / Language *45CFR46.111

24. Why Evaluate Scientific Merit and Research Design? Research must have sound design and not unnecessarily expose subjects to risk. [DHHS Guidance 45 CFR 46.111 Criteria for IRB approval] It is unethical to put subjects at risk or even to inconvenience them in a flawed study. Research should advance scientific understanding and promote human welfare. [1993 Protecting Human Research Subjects: Institutional Review Board Guidebook (Chapter IV)]

25. Expectations: Research Ethics Researchers and Non-Research Community must pay attention to ethics in own work, teaching, and advisory roles. Modern research is not a solitary activity Research always takes play within a social context. Illicit or unwise research activities lead to negative publicity, legal liability, and toxic political fallout

26. What is iStar? Online system for submission, tracking and review of IRB applications To request a user account, go to http://oprs.usc.edu/review/istar/ and click on “Request an iStar Account” Participating IRBs: HSIRB, UPIRB, CHLA

27. Sandbox http://istar.usc.edu

28. What is CITI (Online Human Subjects Education)? CITI—Collaborative Institutional Training Initiative Human Subjects Training Course (+ RCR and GCP) Modules and quizzes on human subjects research ethics, principles, laws and regulations Available 24/7 from any computer Can access course multiple times CITI Helpdesk: citi@usc.edu or 213.821.5272 CITI FAQs: http://oprs.usc.edu/education/citi/

29. CITI Homepage: www.citiprogram.org

30. OPRS/IRB Websites, booklets, videos: http://oprs.usc.edu/education/booklets/ Sample studies, consent templates / information sheets: http://oprs.usc.edu/review/forms/ Federal Human Subjects Regulations www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html HSR Resources

31. Federal Offices Office of Research Integrity (ORI) http://ori.hhs.gov National Institute of Health (NIH) www.nih.gov Public Health Service (PHS) www.usphs.gov National Science Foundations (NSF) www.nsf.gov

32. Who Can I Contact for Help? www.usc.edu/oprs University Park Campus IRB upirb@usc.edu (213) 821-5272 3720 S. Flower Street Credit Union Building (CUB), #301 Los Angeles, CA 90089 http://oprs.usc.edu/upirb/ Health Sciences Campus IRB irb@usc.edu (323) 223- 2340 General Hospital, Suite 4700 1200 North State Street Los Angeles, CA 90033 http://oprs.usc.edu/hsirb/ Office for the Protection of Research Subjects oprs@usc.edu (213) 821-1154 3720 South Flower, Third Floor Los Angeles, CA 90089-0706 http://oprs.usc.edu/

33. HSR Discussion Have you/do you know anyone who has participated in a research study? What kind of study was it? If you were a research participant what are your expectations regarding treatment by study staff and adequate information about study? As a researcher, how can you ensure adequate information is provided to the participant? What is your view of the IRB? What is the most recent article you have read in mass media about some revelations about research or research projects? Would such media attention dissuade you from enrolling in a study? Why would you want to join a research study? Why would anyone join one? If you are conducting research elsewhere, can you be certain that rules and laws in other countries are the same as ours? Should you follow their rules if different? (e.g. the age of minors in consent, publication) If you are an international student is anyone expecting you to learn the rules here? Do I need consent/permission from an online forum (e.g. blogger, facebook) if I want to use their posts for my research data?

34. The End

35. Havasupai Indian Tribe Blood Journey http://www.nytimes.com/video/2010/04/21/us/124 7467672743/blood-journey.html (6:02 min) http://www.nytimes.com/video/2010/04/21/us/124 7467672743/blood-journey.html