Research Matters: An Introduction to IRBs and Research at Vanderbilt

1. Research Matters: An Introduction to IRBs and Research at Vanderbilt Shannon Simmons BA., CIP Regulatory Compliance Analyst IV Vanderbilt Human Research Protections Program April 11, 2014

2. Outline • Overview of the IRB • Type of Research and Reviews • Consent Documents and Processes • Vulnerable Populations • Components of an IRB Submission

3. History and Ethical Principles • In the past, fundamental rights of human subjects were violated by researchers.

4. Tuskegee Syphilis Experiment (1932-1972) Monster Study Stuttering (1930s) Nuremberg War Crime Trials (1946) Nazi German Army Willowbrook State Hospital (1956) Cincinnati Radiation Experiments (1960) Timeline of Historical Events

5. Timeline of Historical Events

6. Timeline of Historical Events • As a result of events such as these, efforts were made to put measures in place to protect the rights and welfare of those individuals participating in research studies.

7. National Research Act (1974) • Created the National Commission for the Protection of Human Subjects. • Charged to identify the ethical principles that should be the guidelines for how research should be conducted on human subjects.

8. The Belmont Report (1979) • The Belmont Report summarizes the basic ethical principles identified by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in 1974. • These three principles are the basis for the Code of Federal Regulations that governs IRB operations and functions.

9. Basic Ethical Principles • Respect for Persons: Individuals should be treated as autonomous agents and vulnerable individuals should be protected. • Beneficence: Maximize benefits and minimize risks. • Justice: Individuals should receive fair and equal distribution of research burdens and benefits.

10. 45 CFR 46 (1991) • Code of Federal Regulations; Basic guidelines for the IRB operations, informed consent, and research compliance. • Upholds the principles of the Belmont Report • Drafted as a result of the Belmont Report and adopted by seventeen Federal agencies active in funding human subjects research; • Also known as “The Common Rule” or Subpart A.

11. 45 CFR 46 (1991) • Defines “research” and “human subject;” • Specifies which activities must be reviewed and those that are exempt; • Mandates the IRB and states its composition;

12. 45 CFR 46 (1991) • Outlines procedures for the review and approval of research; • Specifies the requirements obtaining informed consent; • Defines special provisions for vulnerable populations. • It is the “guidelines” for what we base our IRB Policy and Procedures.

13. Institutional Review Boards • Overseen by the Office of Human Research Protections (OHRP), which is under the Department of Health and Human Services (DHHS). • OHRP is separate from the Food and Drug Administration (FDA), which has its own set of regulations. • The mission of an IRB is to ensure the protection, safety, and welfare of human subjects. • Each IRB Committee is composed of scientists, non-scientists, and community members.

14. IRB Oversight and Review • Non-human Subject and Non-research • Human Subjects Research • Data and Specimen Repositories • Humanitarian Use Devices • Emergency Use of Investigational Drugs • Case Studies • Advertisements • Pilot Studies • Amendments to Approved Research • Non Compliance and Adverse Events • Continuing Reviews

15. IRB Oversight and Review • Examples of types of studies that are reviewed by the IRB: • Educational (Comparing teaching methods, surveying on teaching and learning practices, learning interventions for various disabilities, quality of care interventions and surveys, etc). • Clinical (New medical procedures, studies on drugs and devices, etc).

16. Types of IRB Determinations • Non-research • Research = systematic investigation designed to develop or contribute to generalizable knowledge. • Case studies • Quality assurance projects • Non-human Subjects • Human subject = a living individual about whom an Investigator obtains data either through intervention or interaction with the individual or identifiable private information. • De-identified specimens from a repository • Publically available database research

17. Types of IRB Determinations • Exempt – 6 categories • Educational tests, surveys, interviews, observations of public behavior • Collection or study of existing data • There are stipulations when children are involved • Expedited – 9 categories; minimal risk • Research on individual or group characteristics • Collection of data from voice, video, or image recordings • Blood draws – Healthy adults 550ml/8wks; < 2 draws/wk • Blood draws- Other and Children 50ml or 3ml/kg in a 8wk period no more than 2 blood draws a week • Standard – greater than minimal risk • Pharmaceutical/drug studies • Device studies • Intervention studies

18. Informed Consent • Informed consent is a process free of coercion or undue influence that continues throughout the course of a study. • Participants should be encouraged to ask questions and should show understanding of what they are agreeing to do as part of the study. • Research participation is voluntary; not required. • Informed Consent is a process that goes beyond just signing a form.

19. Informed Consent • The eight basic elements of consent: • A statement that the study involves research, the purpose and duration, and any experimental procedures; • A description of any foreseeable risks; • A description of any benefits; • A disclosure of alternative treatments or procedures; • A statement describing the confidentiality and maintaining of records; • A statement of offered compensation or treatments if injury occurs; • An explanation of whom to contact with questions about the study; • A statement that participation is voluntary, the subject may withdraw at any time, and refusing to participate involves no penalty to the subject. Note: There is a ninth element that include the clinicaltrials.gov language, but that is only for FDA regulated studies.

20. Informed Consent • The six additional elements of consent: • A statement that the research may involve risks that are unforeseeable; • Circumstances under which the subject’s participation may be terminated by the Investigator; • Any additional costs associated with participation in the study; • The consequences of a subject’s decision to withdraw from the study; • A statement that significant new findings will be provided to the subject; • The number of subjects involved in the study.

21. Informed Consent • Should be written in 2nd person; • Not valid unless the participant understands the information that has been provided; • The investigator must consider subject population, type of information, and circumstances under which obtaining consent. • Consent documents are written in simple language that subjects can understand (under 6, 7-12, 13-17, adult).

22. Vulnerable Populations • Subpart B • Pregnant Women, Human Fetuses, and Neonates • Subpart C • Prisoners • Reviewed by the full committee that includes a prisoner advocate/representative • Subpart D • Children

23. Investigator Oversight • The Investigator is ultimately responsible for how the study data is collected, subjects are monitored, and study activities are conducted no matter if someone else on the research staff is appointed to fulfill the investigator’s role. • The Investigator is the ultimate protector of the participant’s rights and safety. • The Investigator is obligated to make sure that participants are informed and consented without undue influence.

24. Investigator Oversight • In a nutshell, the PI is responsible for: • Human Subject Protection • Training • Conflict of Interest • IRB Approval • IND/IDE • Study Conduct • Informed Consent • Amendments • Continuing Review • Data Safety Monitoring • Adverse Events • Complaints • Record Retention In other words…EVERYTHING!

25. Where do you start?

26. Investigator and KSP Training • Must complete the required human subjects training before submitting to the IRB. Any key study personnel (KSP) must also complete training. • Key study personnel is anyone who will have a significant involvement in the planning, conducting, and analysis of any activity that will involve human research participants • CITI Program – http://www.citiprogram.org

27. Investigator and KSP Training • Initial Human Subjects Training • Must complete one of the two “Basic” Courses • Group 1: Biomedical Research Investigators and Key Study Personnel Or • Group 2: Social Behavioral Research Investigators and Key Study Personnel ***Your department may require additional courses that you may have to take, but the IRB for your “Initial” training only requires one of the above modules to be taken.

28. Investigator and KSP Training • Continuing IRB Education/Training • Must complete at least one hour annually. • One additional CITI module (Refresher, Good Clinical Practice, or Responsible Conduct of Research) course or attend an IRB workshop (e.g., News You Can Use, IRB Essentials, etc.).

29. Timing is Everything • Start your project NOW. It’s never too early to start planning. • Allow yourself more time than you think you need. • IRB review may take longer than anticipated depending on the complexity of your study. We usually say allow yourself 4-6 weeks. • Respond promptly to correspondence from the IRB. • If you plan to travel abroad or to an off-site location, make sure you have all the pieces in place before you leave. Please do not submit your project to the IRB on Monday and say you’re leaving on Friday.

30. Use the Resources Available • Work with Investigators, Sponsors, study personnel, and others involved with the study. • Talk to other people that have previously gone through the IRB process. • Call the IRB to set up an appointment to speak with someone about your project. • Talk to someone in the Biostatistics department and attend one of the weekly clinics. • Get help with literature searches in the Eskind library.

31. Putting Your Proposal Together • A typical proposal/submission includes: an application, a consent form, a protocol, and additional supporting documents (e.g., questionnaires, advertisements, brochures, interview guides, etc.). • Exempt applications do not require consent, but we do ask that an information letter be created if interacting with participants for the study. • All of the forms you may need are available on the IRB website. • Submit your study electronically through DISCOVR-E. • Slide shows and step-by-step video tutorials are available on the IRB website.

32. The Review Process • Once your study is sent to the IRB, it will go through the “pre-review” process. • When your study is ready, it will be sent out for review (Exempt or Expedited) or put on the next available agenda (Standard). • When the review is complete, you will receive a letter from the IRB through DISCOVR-E with an update on the status of your study (Approved, Approved Pending, or Deferred). • If your study is approved, no other action is needed on your part. If your study is approved pending or deferred, you must make the requested changes and submit the changes to the IRB for review. • After your study is approved, any changes you want to make must be submitted as an amendment to the study prior to implementation. Any changes to Exempt studies must be done within the first year. • Expedited and Standard studies must be reviewed at least once per year (i.e., Continuing Review).

33. Points to Consider • Simple research is good research. • Be aware of working with vulnerable populations (e.g., children, prisoners, etc.). • Allow ample time for International and multi-site studies. • Ensure the consent documents are written in simple language that subjects can understand (under 6, 7-12, 13-17, adult). • When in doubt, ask questions and don’t hesitate to contact the IRB.

34. Contact Information • 322-2918 – IRB Front Office • http://www.mc.vanderbilt.edu/irb/ • shannon.d.simmons@vanderbilt.edu

35. Questions?