Institutional Review Boards (IRBs) and Human Subjects Research Protection Programs (HRPP) A SHORT COURSE

1. Institutional Review Boards (IRBs) and Human Subjects Research Protection Programs (HRPP)A SHORT COURSE

2. Course Content: Part 1: Brief Description of the IRB and Research at Tulane University Part 2: IRB Support Staff Functions Part 3: Researcher Responsibilities Part 4: How to submit items for review by the IRB Part 5: Brief discussion about the Informed Consent Process

3. Part 1: Brief Description of the IRB and Research at Tulane University

4. What is an IRB? • IRB = Institutional Review Board Consists of: • At least 5 members • At least 1 member must have a scientific background • At least 1 must be a non-scientist (1 non-scientist must attend every meeting to achieve quorum) • At least 1 non-affiliated member (not affiliated with Tulane) • Members should have expertise in the research that will be reviewed

5. IRBs are Regulated by State and Federal Regulations • Federal Regulations: FDA (Food and Drug Administration, Title 21 CFR) and OHRP (Office of Human Research Protection, Title 45 CFR Part 46) • Also, the IRB must adhere to any Louisiana Law that applies to Human Subjects Research

6. Why is Research so heavily Regulated? The history of Research has not always been one of ethics and regulations. Nazi War Crimes and the Nuremberg Trials (1945-1946) and the Tuskegee Syphilis Study (1932-1972) are examples of this.

7. The Modern IRB is Born: • In 1974, the National Research Act was enacted by US Congress. It created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to oversee and regulate the use of human experimentation in medicine. This Act was developed as partly a response to the disastrous Tuskegee Syphilis Study. • The National Research Act mandated specific requirements for institutional review committees which became known as Institutional Review Boards (IRBs).

8. The Modern IRB is Born: • In 1979, the Belmont Report provided guidance as to how the new rules should be applied. The Belmont Report defined the three philosophical principles relevant to research: • Respect for Persons: Adequate information must be provided to subjects of research and voluntarily consent must be obtained. • Beneficence: Harm to subjects must be minimized and benefits must be maximized. • Justice: The Selection of Subjects must be fair and justified.

9. The Primary Concern of the Institutional Review Board (IRB) is to Protect the Rights and Welfare of Research Participants.

10. The Main Purpose of IRB Review: • To Review Research in accordance with the Criteria for Approval set forth in Section 46.111 of the Federal Regulations Including: • Assessing the risk/benefit ratio • Ensuring that informed consent is obtained in an appropriate manner • Verifying that recruitment methods/materials are not misleading or coercive • Ensuring that the selection of subjects is equitable and justified and other criteria

11. Research at Tulane University: • Tulane has 2 IRBs: • A Biomedical IRB on the Downtown Campus and a Social/Behavioral IRB on the Uptown Campus • The Tulane University Research Program is considered to be of medium size when compared across the country. • Currently, Tulane has approximately 1,000 active protocols

12. Tulane IRB Meetings and Members: • The Biomedical IRB holds 2 meetings per month (usually the 2nd and 4th Thursday of each month) • The Social/Behavioral IRB holds meetings once per month (usually on the last Tuesday of the month) • Tulane’s IRBs are made up of physicians, PhDs, pharmacists, nurses, non-scientists, and community members who volunteer their time to review human subject research proposals.

13. Accreditation of the Human Research Protection Program • Tulane University is currently seeking accreditation of our human research protection program from AAHRPP (The Association for the Accreditation of Human Research Protection Programs, www.aahrpp.org) • This accreditation seeks to accredit the entire human research protection program for all of Tulane University, not just the IRBs.

14. Part 2: Human Research Protections Office

15. Tulane University’s Human Research Protection Program Hierarchy: • Dr. Laura Levy, Sr. VP of Research Institutional Official • Roxanne Johnson, MSPH Director, HRPP • Brian Weimer, JD Research Compliance Officer • Mark A. James, PhD. Chair, Biomedical IRB • C. Chrisman Wilson, PhD. Chair, Social/Behavioral IRB

16. Who are we and what do we do? The HRPO is made up of Coordinators who: • Perform preliminary reviews of all submissions to the office for completeness and accuracy (Initial Submissions, Continuing Reviews, Adverse Events, Amendments, etc) • Process, maintain, and update all submissions within the HRPO database system • Acts as a communication liaison between the IRBs and Investigators • Prepare the IRB meeting agendas and distribute review materials to IRB members • Transcribes the IRB meeting minutes and follows up with investigators with IRB requests for approval • Serve as a resource to the research community of Tulane University

17. Part 3: Researcher Responsibilities

18. Responsibility of the Primary Investigator: • All research personnel are required to complete the online Human Subjects CITI Training Course at www.citiprogram.org. • Recertification of this Training is required every 3 years. • It is also the responsibility of the PI to know and understand the regulations and policies prior to initiating any human research. • The PI must acknowledge and accept their role to protect the rights and welfare of research subjects by complying with all applicable Regulations.

19. Additional Responsibilities of the Primary Investigator: • Ensure that the research activities are carried out according to the IRB approved protocol • Protect subject confidentiality by storing electronic research data on password protected computers, and paper data in locked cabinets within locked offices • Follow HIPAA regulations when the research involves the use or disclosure of Protected Health Information (PHI) and obtain authorization from prospective subjects • Ensure that only IRB approved recruitment materials and research authorizations are used • Provide signed copies of consent and authorization forms to research subjects and keep the originals in secured research files • When appropriate, place a copy of the consent form and authorization in the subject’s medical record

20. Part 4: The Submission Process

21. Submission to the IRB: This section will cover: • Initial Submissions • Continuing Reviews • Amendments • Unanticipated Problems/Adverse Events • Protocol Deviations

22. Submission to the IRB: • Tulane University has adopted an electronic, Internet based submission system entitled IRBNet • Researchers are required to register at www.irbnet.org • All Forms can be found on this website for submission A Users Guide to using IRBNet is on our website at: http://tulane.edu/asvpr/irb/irbnet-electronic-submission-system.cfm • Here, you can access the Users Guide, watch a tutorial video of how to submit an initial submission, and access policies and procedures on the use of IRBNet

23. How to submit an Application to the IRB: 1. DEVELOP A RESEARCH PROTOCOL This may come from a grant, an Industry Sponsored protocol, or may be Investigator Initiated. Tips for Writing a Protocol are located on IRBNet. 2. OBTAIN THE REQUIRED TULANE IRB FORMS Fill out either the Biomedical or Social/Behavioral Application Form for IRB Review. Adhere to the Initial Submission Checklist on IRBNet to complete the submission. 3. DETERMINE WHEN THE APPLICATION IS DUE Deadlines for are posted on the IRB website.

24. How to submit an Application to the IRB: 4. DO YOU NEED FULL BOARD, EXPEDITED, OR EXEMPT REVIEW? Full board review is needed for protocols that are greater than minimal risk and Exempt/Expedited review is for protocols of minimal risk. More detail concerning the Regulations is on our website. Reminder: Exempt/Expedited protocols do not have a deadline; they are reviewed on an ongoing basis. 5. SUBMIT THE COMPLETED APPLICATION TO THE HUMAN RESEARCH PROTECTIONS OFFICE Register and submit the Application and all other applicable information via IRBNet at www.irbnet.org

25. The IRB Review Process: What happens after an Application is submitted? • The IRB staff reviews the Application for accuracy and completeness and after the application is accepted, it is processed for review. • Exempt/Expedited protocols are reviewed by the Director of the IRB, one of the IRB Chairs, or any member of one of the two IRBs. The PI will be contacted with either a Decision Letter (usually an Approval Letter or a Deferral Letter stating the changes needed to the Submission before Final Approval can be granted). • Full Board protocols are placed on the next applicable IRB Meeting for discussion and a decision is voted on.

26. The IRB Review Process: What happens after an Application is submitted? • After the IRB Meeting, the IRB staff prepares the Minutes from the Meeting and sends out Decision Letters. If Approved, the Research can begin after receipt of the Approval Letter. • If Deferred, Investigators have 3 months to make the committee required changes and return any requested information/clarifications to the Human Research Protections Office. • Depending upon the Deferral, (for Minor or Major Modifications) the Modifications may be Expedited or may have to be reviewed again by the Convened IRB.

27. INVESTIGATORS CANNOT BEGIN ANY PROJECT INVOLVING HUMAN SUBJECTS UNTIL IRB APPROVAL HAS BEEN GRANTED.

28. Continuing Review: • Projects are typically approved for a period up to 12 months. The IRB may require a more frequent continuing review depending on the level of risk. • Before IRB approval expires, a courtesy notice of expiration is sent to the PI. • It is ultimately the PIs responsibility to submit the continuing review report in a timely fashion to endure a lapse in IRB approval does not occur.

29. Continuing Review: • Continuing Review Forms and are available on IRBNet. • If the IRB does not receive a complete and accurate Continuing Review Submission, the protocol will go into a Lapse period and will be permanently closed after 30 days.

30. Amendments: Revisions to Approved Protocols Steps of Submission: • Determine which aspects of the study will be revised (e.g. protocol, consent form, advertisements, personnel, etc.) • Obtain the Amendment Form for IRB review from IRBNet and submit with required attachments.

31. Amendments: Revisions to Approved Protocols If the revision includes information that must be communicated to currently enrolled subjects (such as altered schedules, revised compensation, newly identified side effects), then you must describe the plan for notifying enrolled subjects and attach any documentation that will be used for this purpose.

32. Amendments: Revisions to Approved Protocols Most minor amendments can be processed via Expedited review. Changes which substantially alter the protocol, or change the Risk/Benefit Ratio require review by the full board. Note: The reviewer of the Amendment has the authority to refer any item to the Convened IRB for review.

33. Reporting Unanticipated Problems: The Principal Investigator must report to the IRB those unanticipated problems/adverse events occurring locally or at another site, that are: specific to a study approved by a Tulane IRB, and that: involve risk to human subjects or others (i.e. subject family members, research staff) and are: Unanticipated, serious, and related to the research activity; Or are: Expected but occurring at a greater frequency or severity than anticipated. Or, The AE indicates an increase in the risk to participants, regardless of severity. • The guidelines for reporting unanticipated problems/adverse events can be found on the IRB website. The Forms can be found on IRBNet.

34. Protocol Deviations: The Principal Investigator must also report to the IRB: • Any deviations from the protocol or an accidental or unintentional change to the protocol taken without prior approval to eliminate apparent immediate hazard to a research participant. • A breach in confidentiality that may involve risk to that individual or others. • A complaint of or from a participant that indicates an unanticipated risk or which cannot be resolved by the research staff. • The Instructions for reporting Protocol Deviations are found on the IRB website. The Form can be found on IRBNet.

35. Part 5: Informed Consent It’s a process…not a form

36. History of Informed Consent: The requirement that researchers obtain informed consent from research subjects originates with Principal 1 of the Belmont Report: Respect for Persons

37. Respect for Persons: • Individuals are treated as autonomous agents. This means that the subjects are not controlled by others and are able to make independent decisions • Persons with diminished autonomy are given protection (e.g. vulnerable subjects such as children, prisoners, mentally disabled) • Consent to participate in research is voluntary and informed

38. Informed Consent Process: Informed consent is a process that begins when you first approach the potential research subject and continues throughout the course of the study.

39. Informed Consent Process: The first contact with research subjects may be through any of the following: • Direct Advertising • Medical Record review to screen for eligible subjects • Physician Referral

40. Informed Consent Process: Obtaining informed consent involves: • Providing information to the subject in a language that is understandable to the subject or their representative • Ensuring that the subject understands what they are being asked to do • Answering any questions that the subject may have • Allowing enough time for the subject to think about the research before consenting to participate • Obtaining voluntary agreement of the subject to participate in the study

41. Informed Consent Process: The consent process continues each time that an investigator has contact with a research subject. The consent dialogue is renewed every time that the study is revised, or if new information becomes available that would impact upon a subject’s decision to participate.

42. Informed Consent Process: Elements of informed consent include: • Information that the study involves research • Risks or Discomforts • Benefits • Alternatives • Confidentiality • Compensation • Contact for additional information • Contact information for research subjects rights • Statement that participation is voluntary

43. Informed Consent Process: Waivers of Informed Consent: Federal regulations allow for some types of research to be conducted without obtaining written informed consent from research subjects. Typically, waivers are only granted for studies that present no greater than minimal risk. The most frequent types of studies that are eligible for waivers are chart reviews and survey studies.

44. Resources for Research and IRBs: www.citiprogram.org www.hhs.ohrp.gov www.fda.gov Contact for Tulane IRB: If you have any questions, you can contact the Tulane HRPO atirbmain@tulane.edu Or, call the office at 504-988-2665.