ORPP&E Workshop: Continuing Review Tools

1. Dial in: (415) 930-5321 Access Code: 638-844-832 Slides in “Handout” Tab ORPP&E Workshop:Continuing Review Tools Soundia A. Duche, MA, MS Chief, Education and Training ORPP&E (formerly PRIDE) January 25, 2019

2. Overview of Session Dial in: (415) 930-5321 Access Code: 638-844-832 Slides in “Handout” Tab • Brief review of continuing review requirements • Why does the IRB conduct continuing review • Frequency of continuing review • Lapses in IRB approval • Substantive and meaningful continuing review • Research that does not require continuing review • Examples of forms • Study closures Cyberseminar on Continuing Review conducted in April 2018: https://www.research.va.gov/pride/cyberseminars/pride-042418.cfm

3. Dial in: (415) 930-5321 Access Code: 638-844-832 Slides in “Handout” Tab Review of Continuing Review Requirements

4. Why Does the IRB Conduct Continuing Review? • Monitoring mechanism that assures that continued safeguards are in place to protect the rights and welfare of study participants • The Common Rule requires it for certain categories of research • Research subject to the pre-2018 Requirements: “An IRB shall conduct continuing review of research covered by this policy at intervals appropriate to the degree of risk, but not less than once per year…” (38 CFR 16.109(e)) • Research subject to the 2018 Requirements that does not fall into one of the categories of research that do not require continuing review (38 CFR 16.109(e)) • FDA regulations require continuing review of all FDA-regulated research (21 CFR 56.108(a))

5. How often must Continuing Review be Conducted? An IRB shall conduct continuing review of research…at intervals appropriate to the degree of risk, not less than once per year, except as described in 38 CFR 16.109(f). (38 CFR 16.109(e))

6. Lapses in IRB Approval If Approval Expires: • Local research office must promptly notify the investigator • Investigator must stop all research activities including, but not limited to • Enrollment of new subjects • Continuation of research interventions or interactions with currently participating subjects • Data analysis (VHA Directive 1200.05, Paragraph 5(g)(19))

7. Lapses in IRB Approval (continued) • Investigator must immediately submit to the IRB Chair a list of research subjects who could be harmed by stopping study interventions or interactions • IRB Chair determines if subjects on the list may continue participating in the research interventions or interactions • Once study approval has expired, IRB re-review and re-approval must occur before the study can resume • The IRB cannot retrospectively grant approval to cover a period of lapsed IRB approval

8. What constitutes Substantive and Meaningful Continuing Review? • All approval criteria continue to be met • Primary focus on whether risks continue to be minimized • The risks to subjects are reasonable in relation to anticipated benefits • The safeguards in place at the time of the original approval are, in fact, adequate to ensure the safety of subjects • Informed consent is accurate and complete • Significant new findings that may affect the subject’s willingness to continue participation are provided to subjects

9. What has to be submitted at Continuing Review? ORD’s Guidance Document on Continuing Review states the following materials should be available to the IRB for review

10. Research that does not require Continuing Review

11. What are the Categories of Research that do not Require Continuing Review by the IRB? • Exempt research • Research subject to the 2018 requirements that is eligible for expedited review • Research subject to the 2018 requirements that has progressed to the point that it only involves one or both of the following: • Data analysis, inclusive of analysis of identifiable private information or identifiable biospecimens; and/or • Access to follow-up clinical data obtained from procedures that subjects undergo as part of clinical care (38 CFR 16.109(f)(1))

12. Conducting Continuing Review on Research that does not require Continuing Review IRBs must document the rationale for conducting continuing review of research that does not require continuing review (38 CFR 16.115(a)(3)) • Project-specific justifications • Justifications for categories of projects • Policy exceptions

13. When should an IRB assess whether a study requires Continuing Review? • At Initial Review • Include justification on reviewer forms or meeting minutes when determining that a project must undergo continuing review even though it falls into one of the categories of research that does not require continuing review • At Continuing Review • Will need to assess each study at the time of continuing review to see if it still requires continuing review • Include justification on review forms or in meeting minutes when determining that a project must continue to undergo continuing review even though it falls into one of the categories of research that does not require continuing review

14. Forms

15. Examples of Continuing Review Forms • Continuing Review Investigator Application • Continuing Review Reviewer Form

16. What options are available for the IRB to track Research that no longer requires Continuing Review? • Request status updates from Investigators • Continuing Review IRB approval criteria do not have to be met as far as content and frequency • IRB approval does not lapse if reports are not submitted and reviewed by a specified date • Status Report Update Form

17. Study Closures

18. Study Closures • The Common Rule and FDA regulations are silent on closing human subject studies • If the study as approved by the IRB or R&D Committee (for exempt studies) is completed, the study should be closed. • How do you determine if closing a study is appropriate? • All research-related interactions and interventions with subjects have ended • Identifiable information and/or identifiable specimens are no longer being obtained, accessed, or analyzed • Any remaining data analysis or manuscript preparation only involves de-identified information • Study closure form

19. Questions

20. Important Links • Revised Common Rule (published January 19, 2017) • Pages 7259 to 7274 contain the Text of the Final Rule • Current Common Rule • VHA Directive 1200.05 • ORD Policies and Guidance Documents • ORD Guidance on Continuing Review (October 22, 2014) • ORPP&E Cyberseminars