Responsible Conduct of Research: Research Regulations

1. Responsible Conduct of Research: Research Regulations Rachel Sheppard, MBA, CCRC, CCRA

2. Goals • Know the resources the University of Louisville offers to help you stay in compliance. • Gain a basic understanding of the regulations governing clinical research. • Learn to ask permission and not forgiveness.

3. Investigator Responsibilities • Gain written IRB approval • Keep a research file and case report for each subject • Conduct study according to written protocol • Be knowledgeable about all interventions • Records of use of drug/device (accountability) • Personally supervise the investigation • Ensure proper billing as it relates to research

4. Investigator Responsibilities (cont.) • Ensure subjects understand what is investigational about the protocol • Ensure all personnel are qualified/trained • Reporting any event that affects research to IRB • Ensure that IRB is compliant with regulations • Maintain approval of study • Record retention

5. Training required • HIPAA fundamentals and security • CITI Biomedical Course • CITI GCP Training (recommended) • Annual SFI disclosure • Blood-borne pathogen Training • Basic Safety Laboratory Training (BSL 1/2) • Additional training

6. Case Reports • Defined as medical information collected and presented on three or fewer patients to highlight an interesting treatment, presentation, or outcome • Authorization if identifiers are present (18 HIPAA) • Done without prior “research” intent • Does not meet the university definition of research • IRB review is required

7. Observational research • Documents required • Complete Waiver • IRB application/approval • Protocol • Data collection forms • Billing Compliance Table (BCT) • Hospital approval (if applicable) • Retrospective or prospective research • If prospective, many other forms…similar to interventional research

8. Interventional research • Documents required • Partial Waiver • Informed Consent Form • Protocol • Research Authorization • IRB application • IBC application (if applicable) • Data collection forms • Billing Compliance Table (BCT) • Hospital approval (if applicable) • If sponsored, many other forms…

9. Documents for Screening and Enrollment • Informed Consent Form (ICF) • Research Authorization (RA) • Partial Waiver • Complete Waiver • What are these documents and their purpose? • Rule of 50 • Documentation of Consenting process

10. Consent Documentation in Records • Name of person obtaining consent • Date of consent • A thorough discussion/explanation of the study was provided and with whom, i.e. subject family members, LAR. • Potential subject and/or LAR was allowed time to ask questions • All questions were answered • Potential subject verbalized understanding of the information provided • Subject or LAR agreed to participate in the study • Subject or LAR signed the ICF and Research Authorization • Study procedures were not performed prior to consent

11. Goals/Responsibilities: Informed Consent Process • Give subject information about the research • Make sure there is adequate time • Determine ability to give informed consent • Cognitive status • Ability to read • Free of undue influence by others • Primary language spoken • Answer all questions • Determine understanding of subject • Obtain voluntary consent; free of coercion • Continue to inform subject

12. Legally Authorized Representative • The individual that has the legal right to consent for the treatment/research • Kentucky State Statute • When to use • Protocol allow • IRB/local law • Call IRB for Guidance • Document, document, document!!!

13. Re-consenting Reasons • Protocol changes • New safety information • New alternative treatments • Pediatric patient reaches 18 • Original consent process not done properly • Potential for capacity to consent may fluctuate • Substantial period since consent elapsed • Other changes mandated by IRB or sponsor

14. Data collection guidelines • Always write with ink; not pencil • Record all data requested or indicate ND or NA • Only make justifiable changes by doing the following: • One line through entry • Record new value • Initial and date • Do not record data outside fields or write on the back • Record data on forms; not on napkins or scrubs • Try to collect specific data; not open-ended fill in the blank • Be consistent

15. Protocol Violations • What is a protocol violation? • Reported based on major and minor • Major – Affects subject rights, safety, wellbeing and/or the completeness, accuracy and reliability of data

16. Reportable to IRB • FDA, OHRP or other agency arrives/notifies for audit • Termination or suspension of research • SAEs/AEs • Protocol violations • New findings • Changes in personnel/procedures • DSMB reports • Breach of confidentiality of data • Incorrect labeling/dosing of test article

17. Reportable to IRB • Discrepancy in accountability of test article • Unauthorized use of PHI • Subject complaints • Incarceration of a subject • Unexpected pregnancy of a subject or partner • Suicide attempt of subject while in research • Death of healthy volunteer within 30 days of participation • Injury of study personnel • Any problem that is unanticipated, related and affects the safety and welfare of subjects

18. Billing Compliance Example • Examples of contingent procedure billing • Schedule of Events important tool

19. What is purpose of HIPAA

20. Using Health Information without Authorization • Treatment, Payment and Operations (TPO) • De-Identified Data • Limited data set with Data use agreement • Activities preparatory to research • Deceased Individuals • Waiver of authorization

21. Waiver of Authorization • 45 CFR 164.512(i) • No more than minimal risk • Plan to protect identifiers • Destroy at earliest opportunity • PHI will not be reused or disclosed except by law • The research cannot be “practicably” conducted without waiver • The research cannot be “practicably” conducted without PHI

22. Texting and Research • Very easy to violate the HIPAA regulations! • Privacy Office can advise on the use of Tigertext app

23. Common IRB findings • Incorrect versions of stamped documents signed • Unapproved versions of documents signed • Lack of documentation of consent process • PI signature after time limit • Failure of PI to sign/date documentation • Incorrect/omitted signatures/dates on documents • LAR not well documented (identity, reason)

24. More common findings • Lapse in IRB approval • Unreported SAEs/protocol violations • Assents signed by parents and not child • No re-consent of 18 year old • Personnel added to study without IRB approval • Missing source documentation • Enrollment numbers not accurate with IRB reports • Lack of policies and procedures for research conduct

25. Governing Authorities for Research

26. Federal Regulatory Agencies • DHHS overarching agency for the following: • FDA (device and drug research) • NIH (peer reviewed research) • OHRP (oversees both FDA and NIH research) • CMS (approval of billing for research procedures) • Code of Federal Regulations • Title 21, Food and Drugs • Title 45, Public Welfare • FDA has adopted ICH Guideline E6 Good Clinical Practice (recommendation) • Office of Civil Rights (enforces HIPAA regulations)

27. Research Structure at UofL and HSC

28. OCRSS assists in the approval process

29. Resources • HSPPO Website http://louisville.edu/research/humansubjects • U of L Investigator Guide • Generic SOPs • ICF process documentation form • Auditors available for educational sessions • 24-hr Hotline: 1-877-852-1167 • Clinical Trial Networks website https://www.ctnbestpractices.org • FDA website http://fda.gov • Association of Clinical Research Professionals http://acrpnet.org • OCRSS Glossary of Terms (handout)

30. Common Initialisms in Research