PRIMER: Human Subjects, Past, Present, and Future Susan Metosky, Arizona State University Debra Murphy, Arizona State University

Objectives Overview Historical Perspective IRB at Arizona State University (ASU) Questions and Answers

Areas and committees supported by Office of Research Integrity and Assurance (ORIA) Responsible Conduct in Research RCR Security Scientific Diving DCB Conflict of Interest IPIRC Biosafety IBC Export Controls Animal Care IACUC Human Subjects IRB Research Integrity and Assurance

Who are our stakeholders? Researchers Federal Government Participants in Research Studies Sponsored Projects and Grants Staff Research Administrators Administrators at Arizona State University Committee members

Protect researchers/university Protect participants Follow Regulations ORIA’s roles

Institutional Review Board (IRB) Reviews all proposed research involving human subjectsresearchhuman subjects Ensures that participants are treated ethically Diverse membership o At least 5 members o Males and Females o One unaffiliated member

“ Those who cannot remember the past are condemned to repeat it." - George Santayana - George Santayana History

20 th Century Research 1972 Syphilis Study Exposed 1966 The Beecher Article (NEJM) 1932 Tuskegee Syphilis Study begins Nuremberg Code 1947 Kefauver-Harris Amendments Food, Drug and Cosmetic Act 1962 Declaration of Helsinki 1964 Belmont Report 1979 Consolidated HHS/FDA Regulations 1981 Common Rule 1991 Nazi Experiments Milgram Study Clinton Apology 1997

Tuskegee Syphilis Study Images taken from: andhttps://

Nazi War Crimes World War II The image is from been the website:

Nuremberg Code (1947) Voluntary consent Anticipate scientific benefits Benefits must outweigh risks Perform animal experiments first Avoid suffering No intentional death or disability Do no harm Subjects can withdraw at any time Investigators must be qualified Research will stop if harm occurs

Belmont Report: Principles and Applications

Federal Regulations 45CFR46 o Federal Policy for the Protection of Human Subjects 21CFR50 (Protection of Human Subjects) o Regulations about FDA-regulated clinical investigations 21CFR56 (Institutional Review Boards) o Regulations about responsibility of IRBs that review FDA-regulated clinical investigations

Approval must be in place prior to initiating research activities or grant expenditure There are 3 types of reviews  Full Board  Expedited  Exempt Rules that apply to all universities

Where was ASU? 4 Federal Audits in recent years

/ Where is the ASU IRB today?

Criteria that the IRB Uses to Evaluate Protocols for Approval Compliance with Federal Regulations and University Policy No risks or risks are minimized Acceptable risk: benefit ratio Equitable selection of subjects Adequate informed consent process Privacy and confidentiality protections Additional safeguards for vulnerable populations

Ways the ASU IRB Works to Minimize Risk To Participants Alternatives o Other procedures that are less risky Precautions o Procedures to decrease the likelihood that harms occur Safeguards o Procedures to deal w/harms if they occur To Researchers Document Everything Follow study procedures Submit any changes to the IRB in writing o Must be approved before implementing Report unexpected events Ask questions

Program Enhancements at ASU Culture of service in addition to culture of compliance Director and IRB Administrator serve as trained IRB alternates o Approve minor changes that do not increase risk o Approve continuations that are closed to enrollment Exempt protocols reviewed by trained staff Increased emphasis on outreach Increase in the number of affiliation agreements

Program Enhancements at ASU Classroom research guidance document Guidelines regarding subject pools Exempt and expedited “grid” documents Special review of “geographic” issues

What are some human subjects issues today? Gene Therapy Trials International Research Nanotechnology Internet Research Chemical and Biological Terrorism Suspension of human subjects programs at universities

Looking to the Future: Advanced Notice of Proposed Rule Making

Questions and Contact Information Debra Murphy (480) Susan Metosky (480)