Human Subjects Working Group Spring Workshop May 7 th , 2008

1. Human Subjects Working Group Spring WorkshopMay 7th, 2008 Department of Health and Human Services (HHS) Office for Human Research Protections (OHRP) Division of Education and Development Lyndi Lahl, MS, RN Michelle Feige, MSW

2. Overview • OHRP’s QIP • Assurance of Compliance • IRB Membership • Investigator Responsibilities

3. OHRP’s Quality Improvement Program (QIP)

4. OHRP’s QI Program (QIP) • OHRP initiated QIP 2002 to assist institutions in assessing and improving their human research protections program • QIP includes two separate components: • A Guided Self Assessment Tool • OHRP QA Consultation – Division of Education and Development staff

5. Goals of OHRP’s QIP • Provide tools to help an institution identify strengths and areas for improvement • Provide detailed review of IRB written procedures and meeting minutes • Clarify regulatory requirements • Explore ways to improve the quality, efficiency, and effectiveness of the human research protection program

6. Attributes of OHRP’s QIP • Voluntary • No Cost • Choice of components: 1) independent self assessment • online guided self assessment tool 2) consultation with OHRP • modes of interaction: on-site visit, videoconference or teleconference

7. QA Self Assessment Tool

8. QA Self Assessment Tool • EVALUATES: Human Research Protection Program • General information about the program including organizational structure • Disclosure and management of conflicts of interest • Handling noncompliance • Workload of the IRB, staffing and resources • General information about the IRB • Education of Chair, members, staff, & investigators

9. QA Self Assessment Tool • EVALUATES: The Institutional Review Board • Review process • Minutes • Post IRB review processes • Approval • Written procedures • Submission process for IRB review • Preparation for full committee review • Preparation for continuing review

10. OHRP QA Consultation

11. Why Seek an OHRP QA Consultation? • A site has made improvements to their HRPP and seeks an OHRP consultation to assess the current status of their program • A site has reached the level of continuing quality improvement of their HRPP and plans to seek accreditation

12. Agenda for an On-Site Consultation DAY 1: DATA COLLECTION • Interviews - Institutional Official - IRB members, Chair(s) - IRB office director(s), administrator, staff - Investigators • Records review - Written policies & procedures & IRB minutes - Research protocol files

13. Agenda for an On-Site Consultation DAY 2: OHRP FEEDBACK • Detailed review of written procedures, IRB minutes, and IRB records • Question and answer period • Exit interview with Institutional Official

14. Agenda for a Video/Teleconference Consultation • Detailed records review • Written policies & procedures and IRB minutes • Limited interaction with personnel • Debriefing of Institutional Official & staff

15. Frequently Discussed Topics • IRB written procedures • IRB minutes • Continuing review • Expedited review, use of exempt categories • Informed consent: documentation of waiver • IRB review of adverse events for multicenter trials • Review of Subparts B, C, D

16. How the OHRP QA Team Handles Noncompliance • Procedural non-compliance - QA team clarifies regulatory requirements and works with institution to develop its corrective action plan - QA team may offer a follow-up interaction • Serious or systemic noncompliance that has or may put the rights and welfare of subjects at risk - Same Steps as above - Recommend self-reporting to OHRP - Notification of Institutional Official & OHRP Director

17. Key Points OHRP’s QIP • Available to all institutions engaged in HHS conducted or supported nonexempt human subjects research • Various methods of conducting consultation • Helps institution to identify areas to improve current human research protections progarm

18. Assurance of Compliance

19. HHS Regulations (45 CFR part 46) HHS will conduct or support non-exempt human subject research only if: • the institution has an OHRP-approved assurance, and • the institution has certified to HHS • research was reviewed and approved by IRB, and • the research will be subject to continuing review §46.103(b) & (f)

20. Institution is Generally Engaged in Human Subjects Research • When employees or agents obtain, for research purposes: • data about the subjects of the research through intervention or interaction with them; or • identifiable private information about them §46.102(d) & (f) • Draft Guidance at:http://www.hhs.gov/ohrp/requests/engage.html

21. Institutions Generally Engaged, Examples: • Administer research interviews or questionnaires • Perform invasive or non-invasive procedures • Manipulate a subject’s environment • Receive or access identifiable private information

22. Institutions Generally Not Engaged, Examples: • Release individually identifiable private information/specimens to another institution • Permit investigators from another institution to use their facilities for research • Provide information about research to prospective subjects • Perform commercial or non-collaborative service

23. Institutional Responsibilities Protect Human Subjects in Research Responsibilities shared by Institutional Officials, IRBs, and Investigators

24. Institutional Assurance • Documentation of institution’s commitment to comply with applicable regulations §46.103(b) & (f) • Generally recognized by other federal departments & agencies • Method of compliance oversight for OHRP • Federalwide Assurance (FWA) – only assurance option

25. Assurance Applications – Extending FWA • Individual Investigator Agreement • independent investigators • investigators at another institution • Assured institution responsible for oversight of research Sample agreement and guidance available at the OHRP website

26. IRB Authorization Agreement • Detail which institution responsible for: • project(s) that will be reviewed by external IRB • monitoring and oversight • Consider including details on termination of agreement • Signed by each institution’s authorized official • Document kept by institutions – must be made available to OHRP, if requested

27. FWA Covers Institutional components Institution’s employees and agents, including students Under limited circumstances, FWA may be extended to individual investigators

28. Assurance Applications - Relying on External IRB Institution responsibility • Written agreement • IRB authorization agreement http://www.hhs.gov/ohrp/humansubjects/assurance/iprotsup.rtf • Ensure research conducted per IRB approved plan • Procedures for reporting to OHRP

29. Institutional Official’s Responsibilities Assure compliance with the: Terms of the Federalwide Assurance

30. Institutional Official’s Responsibilities (cont’d) • Set the "tone" for an institutional culture promoting ethical conduct of research • Support IRB actions & determinations • Ensure that investigators fulfill their responsibilities • Support training/education opportunities for staff

31. Additional Administrative Considerations • Applicability of assurance • Staffing and support • Administrative conflict of interest • Review by additional committees

32. Key PointsAssurance of Compliance • There are many institutional responsibilities when engaged in human subjects research • OHRP holds FWA-holding institution responsible for compliance • Read and understand the terms of FWA assurance • Protecting human subjects is a shared responsibility

33. IRB Membership

34. Members • Minimum of 5 members • Experience and Expertise • Diversity of Members

35. Regulatory Membership Requirements • Minimum one scientist member • Minimum one non-scientist member • Roles of scientist vs. non-scientist • Minimum one nonaffiliated member

36. Special IRB Members • Prisoner representatives • Alternate members • identify pairing of alternate and primary member(s) • appropriate expertise • substitute for entire meeting or any portion of meeting • Expert Consultant

37. IRB Member Conflict of Interest • Investigators on the protocol, financial conflict, other • Conflicted members do not contribute to the quorum • May provide information requested by the IRB • Recusal from IRB’s deliberations and voting

38. IRB Membership Selection & Retention • Who makes selection • Length of tenure • Reasons for termination • Retention strategies

39. IRB Roster (IRB Registration) Members identified by: • Name • Earned degree • Representative capacity • Indication of experience • Employment or other relationship between member and institution §46.103(b)(3)

40. Key PointsIRB Membership • Meet regulatory membership requirements • Alternate member paired to primary member • IRB member conflict of interest must be addressed • Update IRB Roster with OHRP

41. Investigator Responsibilities

42. Protecting Human Subjects is a Shared Responsibility Institution IRB Investigator Subjects Research Team Sponsor Advocates Family Government Public

43. Investigator Responsibility #1 Comply with relevant Federal regulations

44. Regulations for Protection of Human Subjects 45 CFR part 46 • Subpart A – basic HHS Policy - “The Common Rule” or Federal Policy • Other federal departments & agencies have adopted • Subpart B - Pregnant Women, Human Fetuses, and Neonates • Subpart C - Prisoners • Subpart D - Children 6

45. Investigator Responsibility #2 Recognize when the regulations apply to planned activities

46. Investigator Responsibility #3 Initial Review

47. Materials Submitted to the IRB • Protocol, grant proposal, informed consent(s) • Recruitment materials and plan • Any IRB mandated or other related documents

48. Understand IRB expectations and policies Provide sufficient information and materials Recognize and manage conflicts of interest Comply with IRB decisions and requirements Respond to IRB requests in a timely fashion Considerations for IRB Review and Approval

49. Investigator Responsibility #4 Prospective IRB review of proposed changes to research No Changes to Research Without IRB Review and Approval

50. Investigator Responsibility #5 Continuing Review