Charles Hite Director, Biomedical & Research Ethics

1. Taking the Plunge:Facilitating and Monitoring Collaborative Researchand IRB Authorization Agreements Charles Hite Director, Biomedical & Research Ethics

2. Why Rely on Another IRB? “The federal system for protecting research subjects was designed decades ago, when most research studies took place at a single institution. These days, if a study is conducted at multiple sites, an ethics review by an institutional review board (IRB) may be repeated many times. This practice has been criticized for both wasting resources and leading to inappropriate delays in the conduct of research.” – Jerry Menikoff, Director OHRP

3. Why Worry? “ The decision to rely on another IRB raises a host of issues ranging in complexity from a simple aversion to giving up institutional control over the IRB review process to believing that an institution is more vulnerable to legal and compliance risks when IRB review is conducted by another organization. The decision to rely on another IRB can even be marked by a fear that an external IRB cannot or will not review research at a standard that is equivalent to or above those of one’s own organization.” – “From Resistance to Reliance,” The HRP Consulting Group.

4. What Do Regulations Say? OHRP: “Cooperative research projects are those projects…which involve more than one institution. …[An] institution participating in a cooperative project may enter into a joint review arrangement, rely upon the review of another qualified IRB, or make similar arrangements for avoiding duplication of effort.” 45 CFR 46.114 FDA: “…institutions involved in multi-institutional studies may use joint review, reliance upon the review of another qualified IRB, or similar arrangements aimed at avoidance of duplication of effort.” 21 CFR 56.114

5. To Rely on External IRB Use…  IRB Authorization Agreement (IAA), also called Reliance Agreement, negotiated and executed  Policies and procedures to delineate responsibilities implemented  External IRB ensures process and ability to addresses “local” issues http://www.hhs.gov/ohrp/index.html

7. Factors to Consider in IAA Purpose of IAA To create a single IRB of Record? Protocol-specific reliance Reduce administrative burden Nature of authorization Complete reliance Partial reliance, e.g., recruitment/consent document Dual IRB Review (Collaborative, Independent, or Concurrent?) Scope of review Exempt Research? Minimal risk trials only? Clinical trials? All studies? Just one study?

8. Case: Carilion-Virginia Tech IAA Tech Researchers Interested in Accessing Carilion Patients/Data Carilion Physician Researches Want to Collaborate with Tech Colleagues Launch of VTC Medical School and Research Institute 3 Years Ago

9. Case: Carilion-Virginia Tech Initially IAA done on individual studies As projects grew, IAA was supplemented with a Memorandum of Understanding MOU basically assigns IRB review according to degree of “engagement” in research and where subjects are recruited and consented Both IRBs can choose to review

10. Issues to Consider in IAAs Accreditation: AAHRPP requires accredited organizations using external IRBs to ensure the external IRB meets AAHRPP standards Does relying institution have ability to mandate its consent template language? Make sure there is agreement on identifying and managing financial conflicts of interest.

11. Issues to Consider… Who is responsible for providing approval notification and what is the time frame? Will approving institution allow for rights to attend meetings? Will it provide minutes? Will approving institution have right to access relying institution if it is conducting for cause/not for cause audits, etc.?

12. Issues to Consider… How does the reviewing institution address local context issues? What are the procedures for managing reportable information and in what time frame, e.g. serious or continuing non-compliance and unanticipated risks?

13. Issues to Consider… Will both Institutions “uncheck the box”? If one site has “checked” the box, and another has not, your OHRP reporting requirements are inconsistent. Consider aligning federal-wide assurances to both extend your assurance to non-federally funded research or neither. HIPAA status When reviewing for a covered entity, if your institution is not a covered entity or if your institution is a hybrid entity, your institution must have the ability to comply with HIPAA, HITECH and related privacy laws. Informed Consent Language on Subject Injury Clinical Trial Agreement indemnification terms are often incorporated into the informed consent Will reviewing IRB allow for a modification to the consent form? In rare instances where Sponsor CTA negotiations cannot achieve agreement, how will you notify the other IRB?

14. Other Models of Review “…Joint review arrangements…” Central IRB Review / Facilitated Review Decentralized Facilitated Review Single IRB Common IRB “…Rely upon the review of another qualified IRB…” Commercial IRB IRB Deferral/Reciprocal Reliance “…Or make similar arrangements…” Private/Public Hybrid Federation Model Network IRB Model

15. CENTRAL IRB Central IRB Model Administration/Documentations • IAA • Written procedures to describe how each implements its responsibilities for the process SITE #1 Local IRB SITE #2 Local IRB SITE #3 Local IRB Central IRB • Responsible for review • Local IRB • • Local IRB assumes responsibility for: • Local context • Review consent • Assure compliance with local laws Example: National Cancer Institute IRB (http://www.ncicirb.org/) 15

16. Independent or Commercial IRB Organized in compliance with OHRP/FDA regs Outsource IRB functions Often for-profit Fee based Offer a range of services in negotiated contract Each participating IRB reviews investigator request to determine if commercial IRB review is appropriate Sometimes type of review allowed is limited, e.g. only phase 3, multi-center industry sponsored trials

17. Acknowledgement Some slides and/or concepts courtesy of: Sabune J. Winkler, JD Director, Regulatory Affairs Operations Harvard Cataylst