1. Continuing Review Presented by: Karen Jeans, PhD, CCRN, CIP Program Analyst, COACH

2. Objectives Describe what is meant by “continuing review” Describe VA requirements for continuing review Calculate dates for continuing review expiration

3. What is Meant by Continuing Review? Term is undefined in the Federal Regulations

4. What is Continuing Review? Monitoring on-going projects thru continuing review at intervals appropriate to the degree of risk, but not less than once per year. VHA Handbook 1200.05, Paragraph 7.(g) page 15 “An IRB shall conduct continuing review of research covered by these regulations at intervals appropriate to the degree of risk, but not less than once per year...” {21 CFR 56.109(f) and 38 CFR 16.109(e)}

5. Criteria for IRB Approval (.111) A. Required determinations: 1. Risks to subjects are minimized (i) By using procedures consistent with sound research design… (ii) When appropriate, using procedures already being performed… 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 B. When appropriate, additional protections for Vulnerable Subjects

6. Continuing Review Decisions Made by the IRB at Continuing Review: Are subjects adequately protected through the current approved protocol? Informed consent issues The informed consent process is appropriate Written informed consent document is accurate and complete Any significant new findings are provided to the subject

7. Continuing Review What is required to be submitted to the IRB by a Principal Investigator at Continuing Review?

8. Continuing Review – VHA Handbook 1200.05 Requirements Brief summary of the research methodology and procedures; Number of subjects entered and withdrawn (including the reason for withdrawal) for the review period and since the inception of the research project; The gender and minority status of those entered into the protocol; Number of subjects considered as members of specific vulnerable populations; A copy of the proposal and all approved amendments; A copy of the current consent document for the IRB to review; A copy of the current HIPAA Authorization document, if separate from the informed consent;

9. Continuing Review – VHA Handbook 1200.05 Requirements Information that may impact on the risk benefit ratio such as AEs, unanticipated problems, and complaints regarding the research; Research findings to date, if available; Summary of the DSMB or DMC meetings (if applicable) or findings based on information collected by the data and safety monitoring plan submitted in the initial proposal; An assurance that all SAEs and UAEs have been reported as required; and New scientific findings in the literature, or other relevant findings, that may impact on the research.

10. Continuing Review – Lapses in IRB Approval - VHA Handbook 1200.05 If the continuing review does not occur within the timeframe set by the IRB, the research is ‘automatically suspended.” NOTE: For suspended research, enrollment for new subjects cannot occur; continuation of research interventions or interactions in already enrolled subjects should only continue when the IRB or IRB Chair, in consultation with the Chief of Staff (COS), finds that it is in the best interest of individual subjects to do so.

11. Continuing Review – Lapses in IRB Approval - VHA Handbook 1200.05 Once notified of the suspension, the PI must immediately submit to the IRB Chair, a list of research subjects for whom suspension of the research would cause harm. The IRB Chair, with appropriate consultation with the Chief of Staff, determines if the subject may continue in the research. If the study is FDA-regulated, the Chief of Staff and IRB Chair must follow FDA requirements in 21 CFR 56.108(b)(3) in making their decision.

12. Continuing Review – VHA Handbook 1200.05 Whose responsibility is it to make sure a protocol does not lapse? Both the Investigator and IRB have different roles

13. Continuing Review – VHA Handbook 1200.05 Notification of Lapse of Approval Sponsoring agent, private sponsor, ORD, ORO, or other Federal agencies must be informed, as appropriate When is it appropriate to notify these agencies?

14. Continuing Review – VA vs. Everyone Else What is the difference between a lapse in approval and a suspension of IRB approval? A lapse in approval is a passive process. A suspension of IRB approval is an active process.

15. Lapse of Approval Following Expiration of Continuing Review Interval Issue #1:What about the investigational pharmacist? Issue #2:What happens to subjects entered into a study during a period when the study’s continuing review approval period lapsed? Issue #3:What happens to subjects enrolled during a period when the study’s continuing review approval lapsed and it was due to an administrative error within the IRB (study requiring review by a convened IRB left off the agenda)?

16. Determination of Continuing Review Dates When Does Continuing Review Expire? The convened IRB meets on March 1, 2007 and approves Study A for a continuing review period of one year pending minor revisions. The revisions are approved by expedited review of the IRB Chairperson on March 7, 2007. The convened IRB meets on March 1, 2006 and approves Study B for a continuing review period of one year pending major revisions. The revisions are reviewed and approved by a convened IRB on April 1, 2006.

17. Determination of Continuing Review Dates Continued… The convened IRB meets on March 1, 2005 and approves Study C for a continuing review period of one year pending major revisions. The revisions are reviewed and approved by a convened IRB on March 1, 2007. The convened IRB meets on March 1, 2006 and approves Study D for a continuing review period of one year pending minor revisions. The revisions are reviewed and approved by a convened IRB (the IRB does not allow expedited review procedures) on April 1, 2007.

18. Annual Revision Date – Keeping the Same Date If continuing review occurs annually, and the IRB performs the continuing review evaluation 30 days before the IRB approval period expires, the IRB may retain the anniversary as the date by which the continuing review must occur.

19. Annual Revision Date – Keeping the Same Date 1.The IRB approves a protocol requiring full board review on March 1, 2006. Continuing review expires on March 1, 2007. 2.The convened IRB reviews the protocol for continuing approval on February 15, 2007 and approves the study for one year. Continuing review expires on March 1, 2008. 3.The convened IRB reviews the protocol on January 27, 2008 and approves the study for one year. Continuing review expires on January 27, 2009.

20. Guidance on Continuing Review Office for Human Research Protections: Guidance on Continuing Review dated January 15, 2007: http://www.hhs.gov/ohrp/humansubjects/guidance/contrev0107.htm