1. Human Subjects Protection: Creation and Maintenance of an IRB Regulatory Requirements & Recommendations 45 CFR part 46 Freda E. Yoder Office for Human Research Protections (OHRP) Department of Health and Human Services (HHS) March 30, 2005 NARCH Researchers - PI & PD Meeting Indian Health Service November 9, 2005

2. Outline Regulatory Background Regulatory Background IRB Membership & Responsibilities IRB Membership & Responsibilities Written IRB Procedures Written IRB Procedures IRB Records IRB Records Resources Resources

3. in Research Regulations for Protection of Human Subjects in Research HHS regulations at Title 46 CFR part 46 – –Subpart A – common rule or federal policy – –Subparts B, C, & D provide additional protections to certain vulnerable classes of subjects

4. Applicability of Regulations Protections apply to all non-exempt human subject research – –conducted or supported by a Federal Department or Agency that has adopted the regulations, OR – –covered by an Assurance

5. Prerequisite for HHS Conduct or Support of Research HHS will conduct or support covered research only if: the institution has an applicable assurance, and only if the institution certifies to the department or agency [conducting/supporting research] that – –IRB has reviewed and approved the research, and – –research will be subject to continuing review 46.103(b)

6. Assurance of Compliance Documentation of institutional commitment to comply with regulation Principal method of compliance oversight for OHRP Other Federal Departments and Agencies accept a Federalwide Assurance on file with OHRP, in lieu of requiring their own Assurance

7. Assurance of Compliance Includes Statement of principle governing conduct of research Statement of principle governing conduct of research Designation of one or more IRB Designation of one or more IRB –established in accordance with the regulations and –for which provisions are made for meeting space meeting space sufficient staff to support the IRB’s review and record keeping duties sufficient staff to support the IRB’s review and record keeping duties List of IRB members & relevant information List of IRB members & relevant information Written IRB & institutional procedures Written IRB & institutional procedures§46.103(b)

8. When is an Assurance Required? Each institution engaged in research, covered by the [Federal] policy, which is conducted or supported by a Federal Department or Agency shall provide written assurance, satisfactory to the Department or Agency head that it will comply with the requirements of the policy. §46.103(a)

9. IRB Membership & Responsibilities

10. Institutional Review Board (IRB) A committee charged with review of covered human subjects research to assure that the subject’s rights and welfare are adequately protected.

11. IRB Members Regulatory criteria for membership: minimum of 5 members minimum of 5 members background & expertise appropriate to review research conducted by institution background & expertise appropriate to review research conducted by institution qualification & diversity … to promote respect for its advice and counsel qualification & diversity … to promote respect for its advice and counsel ability to ascertain acceptability of research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice ability to ascertain acceptability of research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice representation for vulnerable subjects, when appropriate representation for vulnerable subjects, when appropriate §46.107(a) §46.107(a)

12. IRB Members (cont) Regulatory criteria for membership: not entirely of same sex and may not consist entirely of members of one profession not entirely of same sex and may not consist entirely of members of one profession at least one with primary concerns in scientific areas & at least one in nonscientific areas at least one with primary concerns in scientific areas & at least one in nonscientific areas at least one not affiliated and not immediate family member of anyone affiliated with institution at least one not affiliated and not immediate family member of anyone affiliated with institution may not participate in review of any project in which member has a conflicting interest may not participate in review of any project in which member has a conflicting interest invite other expert to supplement review §46.107(b-f) invite other expert to supplement review §46.107(b-f)

13. Scientist vs. Non-Scientist Scientists include: individuals whose training, background, and occupation would incline them to view scientific activities from the standpoint of a behavioral or biomedical research discipline Non-Scientists include: anyone whose primary concerns are in non-scientific areas

14. IRB Responsibilities, among others Review covered research Must be substantive Criteria for approval at §46.111 (and if applicable, subparts B, C, and D) must be satisfied for all covered research Authority to approve, require modifications, or disapprove all covered research §46.109(a) Authority to suspend or terminate approval of research – –not conducted in compliance – –associated with unexpected serious harm to subjects

15. IRB Responsibilities, among others Type of Review Review at convened meeting of IRB – –majority of members present, including non- scientist – –review & vote on each protocol separately – –majority present must vote in favor, to approve – –notify investigators & institution in writing of IRB action/determinations

16. IRB Responsibilities, among others Type of Review, cont. Expedited review consistent with §46.110 – –may be used for minor modifications to approved research research no greater than minimal risk & fits category on list (see resource slide) – –review by chair or by one or more experienced IRB member – –authority to approve - may not disapprove – –advise all members of approvals – –notify investigators & institution in writing of IRB action/determinations

17. IRB Responsibilities, among others (cont) When must IRB review research? – –initial review – –continuing review – –prior to initiation of changes to approved research When may expedited review be used? – –initial review – categories 1 through 7 – –continuing review – categories 8 & 9 – –minor changes to approved research

18. Written IRB Procedures § 46.103(b)(4-5) OHRP Guidance at: http://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702.htm

19. Required Elements Procedures IRB will follow for: conducting initial review of research conducting initial review of research conducting continuing review of research conducting continuing review of research reporting the IRB’s findings and actions to investigators and the institution reporting the IRB’s findings and actions to investigators and the institution§46.103(b)(4)(i)

20. Operational Details Initial & continuing review - description of: any primary reviewer system any primary reviewer system documents distributed for review & timing documents distributed for review & timing expedited review procedure expedited review procedure any processes supplementing IRB review any processes supplementing IRB review range of possible actions by the IRB range of possible actions by the IRB

21. Operational Details Reporting IRB actions - description of: how notify investigator & how address investigator response how notify investigator & how address investigator response which institutional official is notified & how accomplished which institutional official is notified & how accomplished

22. Required Elements Procedures for: determining which projects require review more often than annually determining which projects require review more often than annually determining which projects need verification from sources other than the investigator that no material changes have occurred since previous IRB review §46.103(b)(4)(ii) determining which projects need verification from sources other than the investigator that no material changes have occurred since previous IRB review §46.103(b)(4)(ii)

23. Required Elements Procedures for: ensuring prompt reporting to the IRB of proposed changes in a research activity ensuring prompt reporting to the IRB of proposed changes in a research activity ensuring that such changes in approved research may not be initiated without IRB review and approval, except when necessary to eliminate apparent immediate hazards to the subject §46.103(b)(4)(iii) ensuring that such changes in approved research may not be initiated without IRB review and approval, except when necessary to eliminate apparent immediate hazards to the subject §46.103(b)(4)(iii)

24. Required Elements Procedures for: ensuring prompt reporting to the IRB, appropriate institutional officials, the Department of Agency head, and OHRP of any ensuring prompt reporting to the IRB, appropriate institutional officials, the Department of Agency head, and OHRP of any –unanticipated problems involving risks to subjects or others –any serious or continuing noncompliance –any suspension or termination of IRB approval §46.101(b)(5)

25. Suggested Additional Elements Among others, any further review by institution any further review by institution procedures for determining exemptions procedures for determining exemptions procedures for implementing other relevant federal, State, & local laws/regulations procedures for implementing other relevant federal, State, & local laws/regulations training and education programs for IRB members, investigators, & staff training and education programs for IRB members, investigators, & staff procedures for selecting IRB members & chairs procedures for selecting IRB members & chairs procedures for dealing with conflict of interest procedures for dealing with conflict of interest

26. Suggested Additional Elements (Cont.) IRB review of research in emergency situations & settings IRB review of research in emergency situations & settings procedures for ensuring IRB knowledge of local research context procedures for ensuring IRB knowledge of local research context description of required elements of informed consent and criteria for altering or waiving these requirements description of required elements of informed consent and criteria for altering or waiving these requirements consideration for date stamping informed consent documents consideration for date stamping informed consent documents procedures for documenting required IRB findings/determinations procedures for documenting required IRB findings/determinations

27. IRB Records – Regulatory Requirements 45 CFR 46.115

28. IRB Records - Regulatory Requirements 1.Copies of –research proposals reviewed –scientific evaluations, if any –approved sample consent documents –progress reports submitted by investigator –reports of injuries to subjects §46.115(a)(1) §46.115(a)(1)

29. IRB Records - Regulatory Requirements (cont.) 2.Minutes of IRB meetings - in sufficient detail to show –attendance at meetings –actions taken by the IRB –votes on actions [separately for each protocol] –basis for requiring changes in or disapproving research, and –a written summary of controverted issues & their resolution §46.115(a)(2) §46.115(a)(2)

30. IRB Records - Regulatory Requirements (cont.) 3.Records of continuing review activities 4.Copies of all correspondence between the IRB and the investigators 5. List of IRB members in the same detail as described in §46.103(b)(3) §46.115(a)(3–5)

31. List of IRB Members Members identified by: name name earned degree earned degree representative capacity representative capacity indication of experience such as board certification, licenses, etc., sufficient to describe each members expected contribution to IRB deliberations, and indication of experience such as board certification, licenses, etc., sufficient to describe each members expected contribution to IRB deliberations, and any employment or other relationship between each member and the institution any employment or other relationship between each member and the institution §46.103(b)(3) §46.103(b)(3)

32. IRB Records - Regulatory Requirements (cont.) 6. Written procedures for the IRB in the same detail as described in §46.103(b)(4) & (5) 7.Statements of significant new findings provided to subjects as required by §46.116(b)(5) §46.115(a)(6–7) §46.115(a)(6–7)

33. OHRP recommends the IRB records also include documentation of any actions, determinations, findings, or requirements made by the IRB

34. IRB Records - Regulatory Requirements (cont.) Retention of records: Records required by the HHS regulations shall be retained for at least 3 years, and records relating to research which is conducted shall be retained for at least 3 years after completion of the research. §46.115(b) §46.115(b)

35. Records Retention (cont.) Some state or local jurisdictions, professional organizations, and institutions may have policies requiring longer retention of research records.

36. IRB Records - Regulatory Requirements (cont.) Accessibility All records shall be accessible for inspection and copying by authorized representatives of the Department or Agency at reasonable times and in a reasonable manner All records shall be accessible for inspection and copying by authorized representatives of the Department or Agency at reasonable times and in a reasonable manner §46.115(b) §46.115(b)

37. Human Subject Protections Subjects Sponsor Advocates IRB Research Team Institutions GovernmentPublic Family Investigator

38. Resources Significant Findings of Noncompliance http://www.hhs.gov/ohrp/compliance/findings.pdf Significant Findings of Noncompliance http://www.hhs.gov/ohrp/compliance/findings.pdf http://www.hhs.gov/ohrp/compliance/findings.pdf Expedited review categories: http://www.hhs.gov/ohrp/humansubjects/guidance/expedited 98.htm Expedited review categories: http://www.hhs.gov/ohrp/humansubjects/guidance/expedited 98.htm http://www.hhs.gov/ohrp/humansubjects/guidance/expedited 98.htm http://www.hhs.gov/ohrp/humansubjects/guidance/expedited 98.htm Institution’s written IRB procedures are posted at web pages http://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702. htm Institution’s written IRB procedures are posted at web pages http://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702. htm http://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702. htm http://www.hhs.gov/ohrp/humansubjects/guidance/irbgd702. htm OHRP educational conferences/meetings OHRP educational conferences/meetings http://www.hhs.gov/ohrp/education/conference.html http://www.hhs.gov/ohrp/education/conference.htmlhttp://www.hhs.gov/ohrp/education/conference.html IRB Guidebook http://www.hhs.gov/ohrp/irb/irb_guidebook.htm IRB Guidebook http://www.hhs.gov/ohrp/irb/irb_guidebook.htm http://www.hhs.gov/ohrp/irb/irb_guidebook.htm

39. Resources Visit OHRP website: http://www.hhs.gov/ohrp http://www.hhs.gov/ohrp Join List Serve: http://www.hhs.gov/ohrp/news/index.html http://www.hhs.gov/ohrp/news/index.html E-mail OHRP: ohrp@osophs.dhhs.gov ohrp@osophs.dhhs.gov Phone #: (240) 453-6900 Fax #:(240) 453-6909