1. An Introduction to Research Compliance AHIA Northwest Regional Conference May 7, 2010 Nicole Jacobs, CHRC Seattle Children's Research Institute

2. Objectives Provide a broad overview of seven different research compliance categories. Describe various topics within each category. Review the structure of federal research oversight of research. Identify key regulations governing research. Highlight research compliance program elements and current compliance issues.

3. Research Compliance Environment Health & Safety Conflicts of Interest Human Subjects Financial Stewardship Research Integrity Research Administration Animal Subjects

4. Research Compliance Conflicts of Interest Research Misconduct Data Management Authorship & Publication Peer Review Mentor/Trainee Relationships Collaborative Relationships Conflicts of Interest Human Subjects Animal Subjects Research Integrity Office of Institutional Assurances Human Subjects Protection Program Institutional Review Board Consent & Assent HIPAA Compliance HIPAA Training & Monitoring Privacy & Security Issues Investigator Initiated Studies FHCRC studies at SCH IRB Protocol & Grant Harmonization Conduct of the Research Office of Animal Care Institutional Animal Care & Use Committee (IACUC) IACUC application review and follow-up Vivarium User Training & Education Regulatory Agency Reporting IACUC Protocol & Grant Harmonization Protocol Deviation Institutional COI Individual Financial COI Conflicts of Commitment IRB Conflict of Interest Intellectual COI (mostly peer review) Personal COI (mostly peer review) Institutional Biosafety Committee (IBC) Radiation Safety Regulated Materials Hazardous Materials Biological Agents All training related to above Accurate PI reporting to IBC Increased Irradiator Controls Pre-Award Proposal Narrative & Budget Agreement Financial Study Document Harmonization Post-Award Subcontractor Monitoring Compliance with Special Terms and Conditions Financial Post Award Monitoring (FPAM) Research Administration Environment Health & Safety Effort Reporting Allowable Costs Cost Sharing Cost Transfers Cost Documentation/Expense Authorization Accurate Direct & Indirect Charges Service/Recharge Centers (Cores) Facilities & Administrative Rate Clinical Research Billing Financial Stewardship

5. Introduction to Research Compliance Research Misconduct Data Acquisition & Management Authorship & Publication Peer Review Mentor/Trainee Relationships Collaborative Relationships Conflicts of Interest Research Integrity Research Integrity is the Responsible Conduct of Research

6. Introduction to Research Compliance Research Misconduct Definition: Fabrication, falsification, plagiarism or other practices that seriously deviate from those that are commonly accepted within the scientific community, in proposing, performing or reviewing research or in reporting research results. It does not include honest error or differences of opinion. Federal Regulations: 42 CFR 93 Define misconduct Require all institutions receiving PHS funding have adequate policies on research misconduct to ensure proper inquiry and investigation of misconduct allegations. Require institutions to provide reports to Office Research Integrity (ORI) Federal Oversight: Office of Research Integrity (ORI) in the Dept. of Health & Human Services (HHS)

7. Introduction to Research Compliance Institutional COI Individual Financial COI Conflicts of Commitment Institutional Review Board (IRB) COI Intellectual COI (mostly peer review) Personal COI (mostly peer review) Conflicts of Interest The focus on Conflicts of Interest is to ensure objectivity in research.

8. Introduction to Research Compliance Conflict of Interest Generally exist when any interest, financial or otherwise, has the potential to compromise or bias professional judgment or objectivity. More specific definitions of conflicts of interest are contained with federal regulations. Federal Regulations: Define conflicts of interest Different thresholds set by PHS and FDA Establish reporting requirements Provide general guidelines for managing conflicts of interest Public Health Service (PHS) Food & Drug Administration (FDA) 42 CFR 50 Subpart F (grants) 21 CFR 54 (investigators) 42 CFR Part 94 (contracts) 21 CFR 56.107 (IRB members) 45 CFR 46.107 (IRB members) Federal Oversight: PHS awarding component (NIH) and/or FDA, depending on funding source and nature of the research.

9. Introduction to Research Compliance Human Subjects Protection Program Institutional Review Board (IRB) Consent & Assent HIPAA Compliance HIPAA Training & Monitoring Privacy & Security Issues Investigator Initiated Studies IRB Protocol & Award (grant or contract) Harmonization Conduct of the Research Protocol Adherence Regulatory Documentation, etc. Human Subject Research

10. Introduction to Research Compliance Belmont Report – Three Key Principles 1. Respect for Persons Informed Consent Privacy & Confidentiality Additional protections for vulnerable populations 2. Beneficence Risks of research are justified by potential benefits to participant or society Maximize benefit, minimize risks 3. Justice Equitable selection of subjects No systematic exclusion of subject who may benefit from the research Human Subject Research

11. Introduction to Research Compliance Human Subject Research Federal Regulations HHS - 45 CFR 46 FDA 21 CFR 50 (informed consent) 21 CFR 56 (institutional review boards) 21 CFR 312 (investigational drugs) 21 CFR 812 (investigational devices) Health Insurance Portability and Accountability Act (HIPAA) HITECH Act in ARRA Also… Other federal privacy laws State Laws IRB Policies Other Institutional Policies may apply

12. Introduction to Research Compliance Human Subject Research Compliance Oversight HHS Office for Human Research Protections (OHRP) FDA Institutional Review Board Institutional Official Federal-wide Assurance Investigator Institutions are required to comply with all regulations that pertain to a study, so if a study falls under jurisdiction of OHRP and FDA, then all regs. must be followed…and they are not always parallel.

13. Introduction to Research Compliance Animal Subject Research Office of Animal Care Institutional Animal Care & Use Committee (IACUC) IACUC application review and follow-up Vivarium User Training & Education Regulatory Agency Reporting IACUC Protocol & Award (grant or contract) Harmonization Protocol Adherence Animal Subjects must be protected to ensure their appropriate care as well as their appropriate use in research.

14. Research Compliance Areas Animal Subject Research Federal Regulatory Agencies 1.U.S. Department of Agriculture 2.Office of Laboratory Animal Welfare (OLAW) (part of PHS) Key Regulations 1.Animal Welfare Act (AWA) USDA oversees and enforces AWA through it Animal & Plant Health Inspection Service (APHIS) 2.PHS Policy on Human Care and Use of Laboratory Animals OLAW oversees and enforces the PHS Policy Key Guidance Guide for the Care and Use of Laboratory Animals

15. Research Compliance Areas Animal Subject Research AWA and PHS Policy Similar in general, different in details Differing applicability, although sometimes both regulations apply Define Institutional Inspection and Reporting requirements Require Institutional Animal Care and Use Committees (IACUC) to provide oversight Define requirements for IACUC’s IACUC Oversight Ongoing review of animal research protocols Semi-annual Review of facility’s program Semiannual inspection of the facility Report findings from reviews and inspections to the Institutional Official (IO) Annual reports to Federal agencies (USDA and OLAW) through the IO

16. Introduction to Research Compliance Pre-Award Proposal Narrative and Budget Agreement Financial Study Document Harmonization Post-Award Subcontractor Monitoring Compliance with Special Terms and Conditions Financial Post Award Monitoring (FPAM - Financial Stewardship) Research Administration There are rules and regulations regarding the administration of PHS funded research.

17. Introduction to Research Compliance Financial Stewardship Effort Reporting Allowable Costs Cost Sharing Cost Transfers Cost Documentation/Expense Authorization Accurate Direct & Indirect Charges Financial Reporting Service/Recharge Centers (Cores) Facilities & Administrative (F&A) Rate Clinical Research Billing All about the proper use of PH research funds, and the appropriate documentation of that use.

18. Introduction to Research Compliance Financial Stewardship Effort Reporting: tool used to enable the proper allocation of salaries to federal awards Allowable Costs: costs charged to federal awards must meet certain criteria. Research studies consist of direct (allowable) costs and indirect (unallowable) costs. Cost Sharing: when a portion of the research projects costs are born by the institution and not the federal government. Any cost sharing must be tracked & documented.. Cost Transfers: moving costs from one award to another after the expense has been incurred. There are restrictions regarding cost transfers. Cost Documentation/Expense Authorization: costs charged to federal awards must be authorized by appropriate individual and documented as allowable Facilities & Administrative (F&A) Rate: F&A costs are considered “overhead” or “indirect” costs. The F&A rate is the indirect costs divided by direct costs. There are specific guidelines as to which costs can be used in calculating this rate.

19. Introduction to Research Compliance Financial Stewardship Regulations Federal Cost Principles OMB Circulars A-21 (2 CFR Part 220) – Universities OMB Circulars A-122 (2 CFR Part 230) – Non-profits 45 CFR Part 74, Appendix E – Hospitals Policies NIH Grants Policy Statement HHS Grants Policy Statement NSF Grants Policy Manual Others Federal Acquisitions Regulation Part 31 (contract cost principles) NIH Policy Notes

20. Introduction to Research Compliance Institutional Biosafety Committee (IBC) Radiation Safety Regulated Materials Hazardous Materials Biological Agents All training related to above Accurate Investigator reporting to IBC Increased Irradiator Controls Research Environment Health & Safety Ensuring a safe research environment, while also protecting the environment from the research materials.

21. Introduction to Research Compliance Regulations are federal, state and local Some of the Regulatory Agencies include: NRC: Nuclear Regulatory Commission DHS: Department of Homeland Security DEA: Drug Enforcement Administration EPA: Environmental Protection Agency OHSA: Occupational Health & Safety Organization State Department of Health State Department of Transportation County Department of Health … and there are many, many more. Research Environment Health & Safety

22. Compliance Area Research Integrity Human Subjects Animal Subjects Conflicts of Interest Research Environment Health & Safety Research Admin. Financial Stewardship Office or Agency ORI NIH OER OHRP FDA OLAW USDA WA Dept of Fish & Wildlife NIH FDA OBA, OSHA, EPA, DEA, CDC, APHIS, US DOT, IATA, US Nuclear Regulatory Commission OPERA CommitteesAd HocIRBIACUC COI Review Board IBC Authority/ Individual Responsible RIO President, Research Institute RIO President and Safety Officer Vice President, Research Ops & Logistics CFO Policies & Regulations 42 CFR 93 45 CFR 689 42 CFR 52h 45 CFR 46 21 CFR 50 21 CFR 56 21 CFR 312 21 CFR 812 HIPAA Privacy Act PHS Policy on Human Care & Use of Laboratory Animals Animal Welfare Act 42 CFR 50 Subpart F 42 CFR 94 60 FR 35820 21 CFR 54 45 CFR 46.107 21 CFR 56.107 42 CFR 73 43 FR 60108 10 CFR NUREG 1556 Sections 817(1) & (2) of USA Patriot Act IFC 45 CFR 74 NIH & HHS Grants Policy Statements 45 CFR 74 OMB A-122 OMB A-21 OMB A-133 OMB A-110 Clinical Trial Policy False Clams Act

23. Introduction to Research Compliance Elements of a Research Compliance Program 1.Ensure compliance with federal, state, and local regulations regarding research and Institution policies 2.Develop and implement policies and procedures as needed for compliance with regulations 3.Conduct effective training and education programs on the responsible conduct of research and current compliance issues 4.Perform compliance risk assessment and internal compliance auditing and monitoring 5.Respond promptly to detected problems and undertake corrective action 6.Enforce compliance standards through well publicized disciplinary guidelines 7.Provide effective lines of communication regarding compliance

24. Introduction to Research Compliance Recent Research Compliance Issues & Risks Effort Reporting Cost Allocation (Proper charging of Direct and Indirect Costs) Cost Sharing Cost Transfers Clinical Research Billing Conflicts of Interest – Individual and Institutional Sub-recipient Monitoring Recharge centers

25. Thank you! Questions?