ORD Human Research Protection Strategy and Direction: The Single IRB Review Mandate

1. ORD Human Research Protection Strategy and Direction: The Single IRB Review Mandate Molly Klote, MD Office of Research and Development IRB-RDC Workshop 20 August 2019

2. WRITING POLICY – CHOKE

3. Front Lines • You are the first line protectors of human subjects in the VHA; in addition: • Researchers • Study Team members • IRB members • RCOs • External Auditors • Research Volunteers and family members

4. Psychological Safety • YOU need to feel like you can say something • YOU cannot assume that someone has thought of the concern you have • YOU need to be educated in the history of research issues • So you can feel justified in speaking up ”Those who do not learn history are doomed to repeat it.” Edmund Burke

5. BE A SME Be the fisherman

6. Constant Evolution of Research Protections Timeline of Events NIH Office of Extramural Research. “Protecting Human Research Participants: History.” https://phrp.nihtraining.com/history/07_history.php (February 2016)

7. CONTEXT & HISTORY 1946-47: Nazi medical studies war crimes trials

8. CONTEXT & HISTORY Studies involving prisoners in the U.S.

9. CONTEXT & HISTORY 1932-1972: PHS Tuskegee Syphilis Study

10. CONTEXT & HISTORY National Research Act (1974)

11. CONTEXT & HISTORY • Radiation experiments report 1986

12. Human Research Protections in the DoD Checkered past - “Atomic Soldiers” • injurious exposures • absence of controls • no informed consent • poor record-keeping LSD experiments • CIA at Fort Detrick • Army at Edgewood Incapacitating Agents • Army Chemical Center • Volunteer participants

13. “Common Rule” • 1991 • IRB review is mandated • Categories established • 1998 Federal register of expedited categories • 2017 • Delay implementation until Jan 2019 • Delay of Single IRB mandate until Jan 2020

14. WHY Single IRB Review??

15. National Movement to Improve Regulatory Efficiencies

16. Applying Risk in Pediatric Research n=188 IRB Chairs Shah et al 2004. “How do IRBs Apply the Federal Risk and Benefit Standards in Pediatric Research?” JAMA 291(4): 476-482.

17. National Movement to Improving Regulatory Efficiencies

18. Single IRB Review Mandate Effective 20 Jan 2020, the 2018 Common Rule requires that, unless adequately justified*, all collaborative research studies, will designate a single IRB to provide the ethical review and ongoing review of a study. Federal agencies may establish the requirements for justification. Justification may also include tribal (Native American) law requirements and/or international norms. VA is struggling with IT requirements to share FISMA mod data outside of VA

19. Opportunity To position VA as the model of effective, compliant, and efficient review of multisite research in US. - Policy Change - Infrastructure Change - Education Overarching system review and changes to benefit all human research review systems and investigators.

20. All Research Review is NOT the “IRB” • Mistaken terminology to call all required review the “IRB” • Data from DOD showed that most delays are investigator delays in response to requests for information

21. 19 VA Facility Visits • IRB is not the rate limiting step to most projects • HR, IT, ISSO, PO, Contracting, and Agreements (OGC) • The role and timing of the R&D committee review needs to be relooked. • Institutional vs RDC vs IRB responsibilities are not clear • Determinations and research oversight as institutional responsibilities • Research Education and Training is needed • FAQs and Guidance are top priority

22. Role of the IRB • Ethical review of a study • 7 or 1(8) in .111 criteria • Waivers of consent • Waivers of HIPAA Authorization • Review of reportable events • Approve, require modifications to secure approval, or disapprove

23. IRB is not the Only Review ISSO Privacy IBC Radiation Safety • RDC • SSRS • Administrative Review

24. Various Institutional Responsibilities

25. Policy Changes • VHA Directive 1200.01: Adjust language to encourage single IRB review; role and timing of R&D committee review and approval; clarify the review of ISSO and Privacy in research; allow electronic determinations • VHA Directive 1200.05: Remove restriction on use of commercial IRBs; allow for use of any non-affiliated IRB where the requisite medical expertise is present to approve biomedical or behavioral research

26. Need IT, Privacy, and ISO to support Project 012020 “Moonshoot” Single IRB Review Efficiency, compliance, interoperability, oversight, trust VHA is Nation’s leader in multisite review 01/20/20 Risk, Variability, Stovepipes Master Agreements with at least 2 commercial IRBs - Oct 2019 Legislative language change RRI VA Electronic Determination Aid – beta version in development 1200.05 and 1200.01 Staffing – Sep 2019 Regional Regulatory Support Network - Operational since March 2019 Strategic Education/Communications – Web site enhancement CIRB feasibility analysis Expand Panels of CIRB 21 Jan 19 New Common Rule Define and socialize institution vs RDC vs IRB roles (THIS EVENT) SMART IRB platform review Analysis of low volume IRBs (<50/year) – review complete Education and Training plan Use of exception to policy to rely on commercial IRB for pharma sponsored trials Release of 1200.05 – Jan 7, 2019 – revision needed Mini “moonshoot” HRPP/IRB SOP harmonization - 21 Dec 2018

27. Single IRB Research Pathway Model Resulting Reviews Prioritization Enabling Effective, compliant and efficient review Standard Review and Approval Identify components Multisite IRB Network Admin Identify Single IRB Priority and Feasibility • -Multisite Training • -Necessary competence • -Assesses IRBs for volume/capacity • -Assign and follows review • Does VA want to do the study? • Is VA capable with right investigators and subjects? • Are other similar/competing projects happening? -Standard form/template/ process • Identify sites to participate in a multisite study • SMART IRB platform • Necessary Agreements - Streamlined review process Electronic Platform (21 CFR 11 compliant) Adapted from the VA Innovation Ecosystem Phase Gate Model and Center for Translation of Rehabilitation Engineering Advances and Technology Commercialization Process

28. VHA Directive 1200.01: ChangedOVERSIGHT of Committees Own IRB Reviews will differ depending upon whether it is a subcommittee or an external committee. National Cancer Institute IRB Subcommittee/Internal IRB External committee/ External IRB MOU VA Facility with Human Subject Program R&D Committee Affiliated IRB The VA Central IRB External committee/ Internal IRB External committee/ External IRB MOU MOU MSA Commercial IRBs External committee/ External IRB

29. Education • Institutional Responsibilities vs IRB responsibilities • Preparing institutions to “let go” of review and re-review • Offloading work from the IRBs to determination algorithms and designated/trained “determination officials” • Creating a network of regulatory support across the VA • Personnel and FAQs

30. Questions? • Are you ready to embrace the changes coming? • Are you willing to be open to new ideas and new ways of doing business? Fasten your seatbelts!!

31. Questions?? Molly Klote, MD 202-443-5605 Mary.klote@va.gov