1. Human Research Protection Program CHR Post-Approval Event Reporting Wednesday, April 11, 2012 Beth Shields, MA, CIP, CCRA Quality Assurance Coordinator Human Research Protection Program Quality Improvement Unit Beth.Shields@ucsf.edu 415-514-3823

2. Human Research Protection Program Outline for Today Types of Post-Approval Events What and How to submit to CHR CHR/QIU role in review of Events Tips for Reporting Using iMedRIS to submit reports Q & A 2

3. Human Research Protection Program Post Approval Event Reporting to CHR – Why? Federal regulations and HRPP policies require reporting of any post-approval event that may meet the HRPP’s definitions of an Unanticipated Problem or Serious and/or Continuous Noncompliance. The CHR determines whether these definitions apply when evaluating post- approval reports. 3

4. Human Research Protection Program Types of Post-Approval Event Reports Serious and/or Unexpected Adverse Events Protocol Violations/Incidents Safety Information: –Investigator Brochure/Package Insert updates –DSMB/DMC Report –Audit Reports –Study Holds Study Close-Out Reports 4

5. Human Research Protection Program Adverse Events (AEs) & Serious Adverse Events (SAEs) Definitions and Determining What To Report and What NOT To Report 5

6. Human Research Protection Program Definition of “Adverse Event” An Adverse Event (AE) is defined as: any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. (emphasis mine)ICH E6 (1.2) However… 6

7. Human Research Protection Program Not all AEs – or even SAEs – need to be reported to the CHR! The CHR has specific criteria describing and defining specifically which AEs should be reported. These criteria are available on the HRPP’s website at http://www.research.ucsf.edu/chr/Guid e/Adverse_Events_Guidelines.asp http://www.research.ucsf.edu/chr/Guid e/Adverse_Events_Guidelines.asp 7

8. Human Research Protection Program Determining What to Report Note: Study sponsors and the FDA have expanded reporting requirements. The VAMC has a shorter timeline (5 days) than UCSF for reporting certain categories of post-approval events (see http://www.research.ucsf.edu/chr/VA/chrV A.asp#considerations) http://www.research.ucsf.edu/chr/VA/chrV A.asp#considerations 8

9. Human Research Protection Program Adverse Events – Internal vs External “Internal” AEs occur in subjects enrolled by a UCSF investigator or at a UCSF- affiliated site. “External” AEs occur in study participants who are enrolled in the same study but at a site not under the control of a UCSF investigator. 9

10. Human Research Protection Program Adverse Events – Internal If … The PI determines event to be : –Definitely; –Probably; or –Possibly Related and –Serious or Unexpected Then… Report the event to the CHR within 10 working days of learning of it 10

11. Human Research Protection Program An AE is “Serious” if it results in one of the following: Death Life-threatening event Inpatient hospitalization or prolonged existing hospitalization (>24 hrs) Persistent or significant disability/incapacity Congenital anomaly/birth defect, or cancer Significant medical, surgical, or other intervention/precaution required to prevent one of the outcomes listed above Event occurred in a gene therapy study 11

12. Human Research Protection Program An AE is Unexpected if it is: More serious than expected More frequent than expected Due to overdose of study medication Due to a protocol violation or AE results in participant’s unexpected withdrawal from study 12

13. Human Research Protection Program Adverse Events – External If… The UCSF PI determines that the event: –Changes the study risks or benefits And/Or –Requires a modification to the CHR Application or the Consent form Then… Report event to CHR within 10 working days of learning of it 13

14. Human Research Protection Program AE’s that do not meet CHR 10-day reporting criteria –Do not submit using AE Reporting Form –For Internal Interventional Studies only, any unrelated death should be reported using the AE Summary Log –If Sponsor requires reporting an event that does not meet CHR criteria, use the AE Summary Log –Attach Log to Continuing Review Submission Form as an “Other Study Document” 14

15. Human Research Protection Program Protocol Violations & Incidents Determining What To Report and What NOT To Report 15

16. Human Research Protection Program Major Protocol Violations and Incidents – Examples Incorrect research treatment or intervention given Enrollment of participant ineligible per CHR-approved protocol Procedure/lab required by protocol not done Procedure/lab done outside the study window Problem with the informed consent or recruitment process 16

17. Human Research Protection Program Major Protocol Violations and Incidents - Examples Significant concern or complaint received Lapse in study approval Loss of adequate resources to conduct study Unauthorized disclosure of private information (e.g. stolen or lost research data, privacy incident) Report any Major Violation/Incident to the CHR within 10 working days of learning of it 17

18. Human Research Protection Program Minor Protocol Violations and Incidents Also known as Protocol Deviations Unapproved changes, deviations, or departures from study design that: –Have not been reviewed and approved by the CHR but –Do not affect participants’ rights, safety, or well-being or impact study data Document in study regulatory binder and develop a Corrective Action Plan (CAP) Do not need to be reported to CHR 18

19. Human Research Protection Program Other Safety Information Determining What To Report and What NOT To Report 19

20. Human Research Protection Program Other Safety Information Updated Investigator Brochure/Package Insert DSMB/DMC Reports Audit Reports with findings Hold on Study Activities Other Safety Information or Updates that may impact UCSF participants Report to the CHR within 10 working days of learning of new information 20

21. Human Research Protection Program Study Close-Out Report Updates the CHR on conduct of the study since the last renewal Required for all studies Report within 10 working days of receiving Sponsor’s Close-Out letter or PI’s decision to close study 21

22. Human Research Protection Program Study Close-Out Report Do not close out a study if: Local enrollment to the study is ongoing Local research-related interventions are ongoing Local participant follow-up is ongoing Data analysis or manuscript preparation requiring use of or access to individually identifiable information is ongoing External sponsor has not given permission to close the study with the CHR. 22

23. Human Research Protection Program CHR Review Process Chair Review & acknowledgement –Chair may request additional information, require a modification, or forward to convened Meeting Convened Committee Review –Determine if the report is an Unanticipated Problem, Serious Non-Compliance and/or Continuing Non-Compliance 23

24. Human Research Protection Program Unanticipated Problem - definition Involves risk to participants or others; Is unexpected and research-related; and The risk exceeds the nature, severity, or frequency described in the –Protocol, –Study consent form, –Investigator’s Brochure, or –Other study information previously reviewed and approved by the CHR. 24

25. Human Research Protection Program Serious Noncompliance Failure to follow state or federal regulations for protection of the rights and welfare of study participants, University policies, or the requirements or determinations of the CHR and that, results in, or indicates a potential for: a significant risk to enrolled or potential participants or others or compromises the effectiveness of the UCSF HRPP or the University 25

26. Human Research Protection Program Continuing Noncompliance A pattern of noncompliance that continues to occur after a report of noncompliance and a corrective action plan have been reviewed and approved by the CHR. –The pattern suggests the likelihood that instances of noncompliance will continue without intervention. 26

27. Human Research Protection Program CHR Regulatory Reporting Requirements Federal Agencies –Office for Human Research Protection (OHRP) –FDA SF Veterans Affairs (if VA study) Associate Vice-Chancellor for Ethics and Compliance UCSF Legal Affairs UCSF Privacy Office Other offices or groups as required by the nature of the study 27

28. Human Research Protection Program Top Tips for Submitting Post Approval Event Reports 28

29. Human Research Protection Program Tips for Post-Approval Event Reporting Before reporting, make sure the event meets CHR 10-day reporting requirements Ask your PI or mentor for guidance Submit using appropriate iMedRIS form Answer all questions on the form completely Include supporting documents, if relevant 29

30. Human Research Protection Program Tips for Post-Approval Event Reporting Explain the context Provide details - dates, lab values, what caused the event, etc Explain the potential consequence, even if nothing happened Provide a comprehensive CAP Do not include PHI in reports Call QIU Analyst of Day and document your QIU consultation If a Privacy Breach, contact the Privacy Office and provide documentation of that communication 30

31. Human Research Protection Program Using iMedRIS to Submit Post Approval Events 31

32. Human Research Protection Program Using iMedRIS to Submit Post- Approval Events Submissions Dashboard & creating Submission Forms Using Submissions History Review by affiliated offices: –Privacy Office –Research Risk Mgmt –SFVAMC 32

33. Human Research Protection Program Provides immediate confirmation of submission Documents CHR review and acknowledgment Links follow-up AE reports to initial event reports Using iMedRIS to Submit Post- Approval Events 33

34. Human Research Protection Program Quality Improvement Unit Lisa Denney, MPH, CIP Assistant Director Quality Improvement Unit Lisa.Denney@ucsf.edu (415) 514-2152 Lisa.Denney@ucsf.edu Beth Shields, MA, CIP, CCRA Quality Assurance Coordinator Beth.Shields@ucsf.edu (415) 514-3823 Beth.Shields@ucsf.edu Laurie Herraiz, RD, CCRP Quality Assurance Coordinator Laurie.Herraiz@ucsf.edu (415) 514-9246 Laurie.Herraiz@ucsf.edu 34

35. Human Research Protection Program Resource Information Guidance for Reporting Post-Approval Events to CHR: –http://www.research.ucsf.edu/chr/Guide/hsppGP.asp#Re portinghttp://www.research.ucsf.edu/chr/Guide/hsppGP.asp#Re porting QIU section of HRPP Website: –http://www.research.ucsf.edu/chr/Qip/hsppQip.asphttp://www.research.ucsf.edu/chr/Qip/hsppQip.asp SFVAMC Guidance: –http://www.research.ucsf.edu/chr/VA/chrVA.asp#consider ationshttp://www.research.ucsf.edu/chr/VA/chrVA.asp#consider ations –Clinical Research Office (415) 221-4810 x6425 Clinical Research Coordinators Website: –http://www.research.ucsf.edu/chr/Train/CRC_Group.asphttp://www.research.ucsf.edu/chr/Train/CRC_Group.asp Affiliate Privacy Office Contact Information: –SFVAMC Elaine Tran, (415) 221-4810; Ext: 2135 –SFGH Philip Katzenberger (415) 206-6210 or main # 206-8000 –SFDPH Privacy Office (415) 206-2354 35

36. Human Research Protection Program Upcoming HRPP Classes “ Recruitment: What Methods Are Appropriate?” Friday, May 4, 1:00 – 3:00 pm iMedRIS Training Classes Managing Approved Studies in iMedRIS (advanced) Thursday, April 12, 10:00 – 11:30 am Introduction to iMedRIS Thursday, April 26, 10:00 am – 12:00 pm See HRPP Website for more education opportunities: http://www.research.ucsf.edu/chr/Train/chrTrain.asp 36

37. Human Research Protection Program Questions? 37