1. Human Research Protection Program & IRB Responsibilities Marisue Cody, PhD Director Center on Advice & Compliance Help

2. Objectives  Describe the shared responsibilities of a facility Human Research Protection Program  Describe the responsibilities for Human Subjects Protection  Explore risks, privacy, & confidentiality review by the IRB

3. HRPPP (Human Research Participant Protection Programs)  Institute of Medicine report 2001 Preserving the Public Trust  Broader system with multiple functional elements  Advocated accreditation of the HRPPP

4. Human Research Protection Program (HRPP)  Shared responsibility Organization Leadership Research Office R&D Committee IT, Privacy, Ethics IRB Investigators and research staff

5. Old model R&D IRB New model: HRPP Director Patient Advocates HPA RCO Radiation Safety ACOS/Education AO DSMB QA/QI Pharmacy Subjects Grants & Contracts Chief of Staff Medical Records Public Affairs R&D Committee IRB Investigators Study Coordinators Conflict of Interest Committee Privacy Office Clinical managers ACOS/R ISO

6. AAHRPP Accreditation Standards Domains  Organization  Research Review Unit  Investigator  Sponsored Research  Participant Outreach Obligations of Obligations to

7. How does accreditation work? Application Site Visit Council on Accreditation Self Evaluation Expert site visitors Tailored to setting Determines Accreditation category

8. Categories of Accreditation  Full AAHRPP accreditation  Qualified AAHRPP accreditation  Accreditation-pending  Accreditation withheld

9. AAHRPP Accreditation Update  74 applications (94 FWAs)  72 site visits (92 FWAs)  53 applications reviewed by AAHRPP Council (65 FWAs)  35 HRPPs accredited (40 FWAs)

10. Institutional Responsibilities

11. Regulatory Guidelines for the Institution  Dept of Health & Human Services – FWA  FDA – none  VA VHA Directive 2003-031 (funding of the facility HRP) VHA Directive 1200 (Facility R&D program) VHA Handbook 1200.1 (R&D Committee)

12. Federalwide Assurance (FWA)  This documents your institutional commitment to comply with the Common Rule.  It is required from each institution “engaged” in covered research: http://www.hhs.gov/ohrp/policy/index.html#engagement

13. Assurance of Compliance (38 CFR part 16.103)  Statement of principles governing the institution  Designation of one or more IRBs  List of IRB members  Written procedures the IRB will follow  Written procedures for reporting unanticipated problems involving risk, and any suspension or termination of IRB approval  Executed by individual authorized to act for the institution

14. Review by institution (38 CFR part 16.112)  Research approved by an IRB may be subject to further review by official of the institution  Those officials MAY NOT approve the research if it is not approved by the IRB

15. IRB Requirements

16. Federal Policy for the Protection of Human Subjects  Originally issued in 1974 as Part 46 of Title 45 of the Code of Federal Regulations (Subpart A) by DHEW  Adopted in 1991 by 17 federal agencies 38 CFR part 16 refers to the VA 45 CFR part 46 refers to DHHS 21 CFR parts 56 (IRB) and 50 (informed consent) refers to the FDA

17. Common Rule and VHA Handbook 1200.5 Common Rule = Regulation Establish IRBs and responsibilities Ensure Informed Consent of Subjects VHA Handbook 1200.5 = Policy Medical Center Responsibilities IRB Composition & Responsibilities Investigator Responsibilities Investigational Drugs & Devices in VA Handbook and Federal Regulations Same regulatory weight (not optional)

18. What is covered?  All research involving human subjects conducted, supported or otherwise subject to regulation by any federal department or agency which takes action to make this policy application. (38 CFR part 16.101)  In the VA, that is all research involving human subjects conducted completely or partially in VA facilities, approved off-site locations, facilities, and/or by VA researchers while on official VA duty time (VHA Handbook 1200.5, p. 6).

19. … a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to “generalizable” knowledge. (38 CFR part 16.102d) Research

20. Human subject … means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual, or (2) identifiable private information

21. IRB Review of Research (38 CFR part 16.109)  Authority to: Approve, require modifications to seek approval, or disapprove  Require that information given to subjects is in compliance with informed consent regulations  Shall require documentation of informed consent or waive documentation  Notify investigators in writing of its decision  Conduct continuing review and have authority to observe consent process and research

22. Additional VHA 1200.5 requirements Prior to initiating research: Research MUST be reviewed and approved by IRB AND R&D, approval must be in writing If approval is contingent on substantive modifications, subsequent review must be by the convened IRB If approval is contingent on specific minor conditions, the IRB chair or designee may approve it on behalf of the IRB

23. Criteria for IRB Approval (VHA Handbook 1200.5) 1.Risks to subjects are minimized 2.Risks are reasonable in relation to benefits 3.Selection of subjects is equitable 4.Informed consent will be sought prospectively 5.Informed consent is appropriately documented 6.Research plan makes adequate provisions for safety monitoring 7.There are adequate provisions to protect privacy and confidentiality 8.Protection of vulnerable subjects 9. Conflict of interest 10. Ensure investigator educational requirements and certifications

24. Criteria for IRB Approval (VHA Handbook 1200.5) 1.Risks to subjects are minimized 2.Risks are reasonable in relation to benefits 3.Selection of subjects is equitable 4.Informed consent will be sought prospectively 5.Informed consent is appropriately documented 6.Research plan makes adequate provisions for safety monitoring 7.There are adequate provisions to protect privacy and confidentiality 8.Protection of vulnerable subjects 9. Conflict of interest 10. Ensure investigator educational requirements and certifications

25. Risk: What is it?  The probability of harm or injury occurring as a result of participation in a research study  Prediction of some future occurrence of harm  Consideration of probabilities: what has happened before?

26. Benefit: What is it?  A valued or desired outcome; an advantage  The probability of hoped for benefits

27. Risk/Benefit Analysis  Risks and benefits are not parallel ideas Risks: often individual, immediate, measurable Benefit: often elusive, future, potential  Need to maintain a favorable balance

28. The Role of the IRB  Review potential risks, discomforts, hazards, or inconveniences of protocol Probability, magnitude, duration, reversibility of risks  Separate risks of research from standard of care risks e.g. Risks of surgery already scheduled  Give special consideration to risks for research involving vulnerable populations Children, mentally impaired, prisoners, others

29. The Role of the IRB (cont.)  Consider hoped for benefits Benefits can take the form of therapy, education, information, resources or empowerment Benefits can be directed at participants, their community, society, medical knowledge, medical technology  Consider if risks reasonable in relation to possible benefits Balancing potential risks to participant/others against possible benefits to participant/society

30. VHA DIRECTIVE 2007-040 November 30, 2007  All human subjects research conducted at the facility is reviewed prior to the research being initiated by an ISO and a Privacy Officer who have been appointed to either the IRB of record or the R&D Committee of record.

31. Privacy & the IRB (VHA Handbook 1605.1) All VHA Investigators conducting VHA- approved research must obtain the authority to use individually-identifiable information as follows: VHA individually-identifiable health information involving non-employee research subjects may be used by a VHA Investigator for research purposes provided there is a prior written authorization. A prior written authorization may be incorporated into an informed consent.

32. Privacy & the IRB (2) VHA individually-identifiable health information involving non-employee research subjects may be used by a VHA Investigator for research purposes when there is an IRB or Privacy Board waiver of authorization in accordance with 45 CFR 164.512(i).

33. Privacy & the IRB  Authorizations  Recruitment

34. Data Security & the IRB (VA Handbook 6500)

35. Data Security & Research  The security policies, procedures, and controls in this handbook apply to all VA employees, contractors, researchers, students, volunteers, representatives of Federal, State, local, or Tribal agencies, and all others authorized access to VA facilities, information systems or information in order to perform a VA authorized activity.

36. Confidentiality  Collection of data  Data transfer  Data storage  Granting access to data

37. Key Points Related to Privacy & IT Security  http://www.research.va.gov/resources/ data-security/docs/Key_Points.pdf http://www.research.va.gov/resources/ data-security/docs/Key_Points.pdf

38. Checklists, Certification Forms & Other Responsibilities  http://www.research.va.gov/resources/data- security/checklists.cfm http://www.research.va.gov/resources/data- security/checklists.cfm  Check these links for specific information for:  Principal Investigators (PIs) Principal Investigators (PIs)  Associate Chief of Staff for Research & Development (ACOS/R&D) or Research Coordinator Associate Chief of Staff for Research & Development (ACOS/R&D) or Research Coordinator  Medical Center Directors Medical Center Directors  VISN Directors VISN Directors