1. VA Research: IRB and R&D Approval Process From Initial Submission, Through the Informed Consent Process and Continuing Review, To Inactivation Kimberly Summers, PharmD Deputy ACOS for Research South Texas Veterans Health Care System Research & Development Service

2. Overview What needs IRB Approval? Types of Review How to Submit New Application Principal Investigator Responsibilities Summary

3. When is STVHCS R&D Approval Needed? R&D Committee approval is required to conduct any and all VA research What constitutes VA research?

4. Definition of VA Research Research sponsored by the VA Research conducted using any property or facility of STVHCS Research conducted by or under the direction of any salaried or without compensation (WOC) employee of the STVHCS during and in connection with her/his STVHCS responsibilities Funds for the research activities are managed by the STVHCS or Biomedical Research Foundation of South Texas Research which recruits subjects at the STVHCS or uses the STVHCS's nonpublic information to identify or contact human research subjects for research purposes (i.e. CPRS)

5. Types of IRB Review Not research or research not involving “human subjects” Human research eligible for exemption Human research (non-exempt) eligible for expedited IRB review Human research (non-exempt) that is not eligible for expedited review and must be reviewed by a convened meeting of the IRB (full IRB board review)

6. Types of IRB Reviews That Require STVHCS R&D Approval Research NOT involving “human subjects” Human research eligible for exemption Human research (non-exempt) eligible for expedited IRB review Human research (non-exempt) that is not eligible for expedited review and must be reviewed by a convened meeting of the IRB

7. Non-Human Research Form available on IRB website Obtaining aggregate data only with no identifiable information Form I required – –Person releasing the information has access to that information as part of their routine duties – –Person releasing the information verifies all information provided is de-identified Still requires R&D submission

8. Types of IRB Reviews That Do NOT Require STVHCS R&D Approval IRB determined to NOT be research – –Quality Improvement Projects – –Case reports – –Meta-analysis of published studies May still require Privacy Officer approval – –Any VA sensitive information – –Personal Health Information is NOT allowed – –Mary Wohl (VA ext 15602; marywohl@va.gov )marywohl@va.gov

9. Training Requirements

10. IRB Required Training All investigators and research staff conducting human research at institutions using the HSC IRB must complete research ethics training provided by the University of Miami, Collaborative IRB Training Initiative (CITI). Details on IRB website - http://research.uthscsa.edu/irb/training.shtml http://research.uthscsa.edu/irb/training.shtml The VA does not recognize the IRB CITI investigator training

11. R&D Required Training The VA requires completion of a different CITI investigator training course – –Must complete the VA training if conducting VA Research – –The HSC recognizes the VA CITI training – –Must be taken annually Information Security 201 for R&D Personnel – –One time only Training required to maintain VA appt – –VA Cyber Security Awareness – –VHA Privacy Policy Web Training – –Must be taken annually

12. VA Research Privileges are Required in Addition to Training Requirements

13. Research Privileges Research credentialing and privileges are required prior to work on any VA protocol Requirements are different for the following groups – –VA Employees – –Fellows, Residents, and Students – –Non-VA investigators or study personnel – –Exempt study staff

14. http://www.southtexas.va.gov/research/

15. Exempt Personnel Study personnel who are not physically conducting research on VA property, only have access to de-identified data and/or not directly working with research subjects – –Examples: lab personnel, data or administrative personnel Requirements – –VA Data Security 201 Training – –Memorandum from PI denoting what their role in the study will be – –Conflict of Interest Form

16. Submission Process

17. IRB Protocol Submission

18. IRB Submission Form K Pre-Notification of the Intent to Conduct Research that includes other InstitutionsPre-Notification of the Intent to Conduct Research that includes other Institutions Required to submit with your IRB applicationRequired to submit with your IRB application Notifies the R&D office of your intent to conduct VA researchNotifies the R&D office of your intent to conduct VA research R&D office signs Form K and returns with link to VA Research websiteR&D office signs Form K and returns with link to VA Research website

19. http://www.southtexas.va.gov/research/

21. R&D Submission Submit a hard copy of all required forms with appropriate signaturesSubmit a hard copy of all required forms with appropriate signatures Original + 7 copies requiredOriginal + 7 copies required All study related documents and required forms must also be submitted electronically on a CDAll study related documents and required forms must also be submitted electronically on a CD

22. R&D Submission Date Submission prior to the first Monday of each month – –Will be reviewed at the following month’s R&D meeting if all forms are completed and administrative stipulations addressed Protocols requiring review by a convened IRB – –One of the following must have occurred prior to application submission to the R&D office IRB administrative review IRB final resubmission Final IRB approval Protocols eligible for IRB expedited or exempt review – –Application submission to the R&D office should be concurrent with IRB submission

23. R&D Administrative Review An appointment with the investigator and/or study coordinator is required to address any administrative stipulations The intent of the meeting is to address, correct, and finalize any administrative stipulations in real time to shorten the overall approval time Any changes required on IRB forms or informed consents can be incorporated into final IRB submissions, addressed at IRB admin review, or must be submitted as an IRB amendment

24. R&D Final Approval All administrative stipulations must be addressed and resubmitted at least one week prior to the R&D Committee Meeting for the protocol to be placed on the agenda – –IRB approval may still be pending at the time of resubmission Final R&D approval can be granted following R&D Committee review when: – –IRB approval is in place – –All R&D Committee stipulations have been addressed

25. IRB and R&D Initial Submission Summary

26. Full IRB Board Review Protocols

27. Exempt and Expedited Protocols

28. R&D Approval Timelines BASELINE R&D REVIEWS SINCE JAN 2009 Time from IRB approval until R&D approval Median72 days34 days Time from R&D meeting until R&D approval Median89 days26 days

29. STVHCS R&D Approval Must have R&D approval letter prior to any of the following being conducted at the VA – –Recruitment – –Obtaining informed consent – –Enrollment – –Providing patient follow up An IRB approval letter does NOT constitute R&D approval

30. Informed Consent Process An IRB approved and stamped VA Informed Consent document does NOT constitute R&D approval IRB approved and stamped informed consent requiredIRB approved and stamped informed consent required –ONLY the most recent IRB approved and stamped consent form can be used to consent subjects Documentation in the medical record requiredDocumentation in the medical record required Scanning of IC document requiredScanning of IC document required

31. Continuing Review and Protocol Modifications

32. Amendments & Modifications Changes in previously approved studies cannot be made without prior IRB review – –Except when necessary to eliminate immediate hazards to a subject Examples of changes requiring IRB approval – –Number subjects consented and enrolled – –Design, methods or procedures – –Study staff, study sites/locations – –Consent procedures, consent document – –Recruitment advertisements, payments

33. Amendments and Modifications PI is responsible for submission to the IRB STVHCS R&D office is notified by the IRB – –All studies identified as VA Research IRB and R&D reviews are combined Any required changes by the IRB or R&D are forwarded by the IRB to the PI Corrective actions are required prior to IRB approval and initiation at the STVHCS

34. Changes in Personnel Personnel list submitted to IRB – –IRB Form B-2 – –VA Form Personnel List for Human Studies For personnel engaged in research conducted at the VA – –IRB will verify with the R&D office that all study personnel have submitted the required documentation and been assigned research privileges at the VA prior to approval of the amendment

35. Continuing Review IRB may approve a study for a period of no longer than 1 year For re-approval, the IRB must review the protocol, any amendments, and a status report including: – –Number of subjects accrued – –Description of adverse events, unanticipated problems, withdrawal of subjects, complaints – –Summary of relevant information – –Copy of current consent document(s)

36. Continuing Review Process Continuing Review of Research Protocols form must be submitted to the VA R&D office – –Contains VA specific information in addition to IRB continuing review form – –Submission of the IRB continuing review form and/or approval letter to the R&D office is NOT required – –R&D office staff coordinate with IRB continuing review team for VA required changes Exempt research – –IRB requires updates every 3 years – –VA continuing review form required at least annually

37. Continuing Review Process Protocol approval at the STVHCS will expire if – –Continuing review is not completed – –Training requirements for the PI are not up-to-date at the time of continuing review Co-investigators and other study personnel will be removed from active protocols if training requirements are not up-to- date Expiration of approval will be corrected upon receipt and satisfactory review and approval of the required documentation

38. Reporting Requirements

39. Unanticipated Problems Involving Risks to Subjects or Others Any incident, experience or outcome that meets all of the following criteriaincident, experience or outcome – –Unexpected (in terms of nature, severity, or frequency) – –Related or possibly related to participation in the research – –Suggests that the research places subjects or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized May be an adverse event or non-adverse event Events reported to the IRB related to VA research are communicated to the R&D and vice versa

40. Reporting Noncompliance Conducting research in a manner that disregards or violates federal regulations, failure to follow the IRB requirements & determinations, or institutional policies and procedures – –In the case of VA research includes the requirements of the VA Handbook 1200.5 Handled by governing IRB Findings of serious or continuing noncompliance reported to: – –OHRP – –FDA if IND/IDE – –ORO (VA Office of Research Oversight)

41. Protocol Inactivation

42. Inactivation of IRB Approval When is it appropriate to inactivate IRB approval? – –Enrollment of new subjects is permanently closed – –Data, private information, and/or clinical specimens are no longer being collected for research purposes (including long term follow up) – –Subjects are no longer being treated under the research protocol (includes no plan for future research treatment) – –Research assessments or procedures are no longer being performed (includes no plan for future research procedures) – –Federal research funding for this study is closed – –If a multi-center study where UTHSCSA is the study operations center or the UTHSCSA investigator is the Lead Investigator, if the study closed at all participating sites – –Data/specimen analysis has been completed locally, or if analysis continues locally and the data has been permanently de-identified

43. Inactivation of R&D Approval

44. Specific IRB Questions Expedited review new studies: – –Rhonda Barnard, MS, CIP 210-567-2372 Full Board review new studies: – –Debbie Etter, Team Leader 210-567-2356 Modifications/Amendments – –Helen Cavazos, Team Leader 210-567-2353 Progress or Final reports: – –Clara Perkins, Team Leader 210-567- 3086

45. Specific R&D Questions New study submissions and modifications/amendments for VA pending studies : – –Angela Casas, (210)617-5300 VA ext 15523 Progress or final reports and modifications/amendments for VA approved studies: – –Tracy Jackson, (210)617-5300 VA ext 15520

46. Questions? Kimberly Summers, PharmD Office: (210) 617-5300 ext 15969 Email: kimberlyk.Summers@va.gov