Use of a Central IRB: McDeavitt to Menikoff, April 13, 2010

Dear Dr. Menikoff:

Carolinas HealthCare System is a large integrated health care system, headquartered in Charlotte, NC, with our own local IRB. We own and operate healthcare facilities throughout North and South Carolina and have an extensive network of full-time faculty and affiliated physicians. Like many institutions we are considering the possible implications of outsourcing portions of IRB oversight to some sponsor-selected IRBs, especially for Phase III/IV industry-sponsored device and drug trials. We write seeking your counsel on the status of the current regulations/guidance regarding such "central" or "external" IRB's, as we understand them.

The FDA has held the IRB-of-record, irrespective of the relationship of that IRB with the research institution/site, accountable for compliance with regulations governing IRB activities. The Office of Human Research Protection (OHRP), on the other hand, has held the "institution" ultimately responsible for IRB activities, and this has led to the concern that an institution using an "external" IRB would be held regulatorily "liable" for non-compliance on the part of an independent external IRB. In our vetting process of several external IRBs, we are receiving mixed messages on their interpretations of the current status of the views of OHRP's on this issue.

The archiving of "Local IRB Review of Multicenter Clinical Trials" and "Local Institutional Review Board (IRB) Review of Multicenter Clinical Trials Sponsored by the Division of Aids (DAIDS) National institute of Allergy and Infectious Diseases (NIAID)" appears to us to suggest that OHRP's policy regarding local IRB review has changed or is changing. Although, OHRP states that "review by a local IRB is not favored over review by a non-local IRB," it does not provide the same level of endorsement that the FDA provided when it stated that the "Agency hopes that sponsors, institutions, institutional review boards (IRBs), and clinical investigators involved in multicenter clinical research will consider the use of a single central IRB." Although the prior guidance documents referenced above have been archived, the signed Federal Wide Assurance [FWA] states that the institution is responsible for ensuring that the "designated IRB(s) will comply with the Terms of the Federal Wide Assurance for Institutions within the United States and possess appropriate knowledge of the local context in which this Institution's research will be conducted."

Additionally, OHRP "Guidance on Engagement of Institutions in Human Subjects Research" states that ''the institution must ensure that the IRB(s) designated under its FWA reviews and approves the part(s) of the research in which the institution is engaged." The OHRP guidance requires a written agreement between IRBs to achieve this level of institutional oversight and places the onus on the institution to ensure that the independent IRBs review "will meet the human subject protection requirements." Absent new guidance from OHRP, the existing guidelines thus seem to indicate that OHRP holds the local institution ultimately accountable for IRB oversight. Without some modification of OHRP expectations, the willingness of local IRB's such as ours to be held fully accountable for decisions and actions taken by external IRB's will likely be low and variable.

Thus, we write asking you to inform us of your current views on this and the likelihood and time frame that OHRP may issue revised guidance pertaining to use of external IRB's and issues of legal liability between central and local IRB's.

Thank you in advance for your anticipated consideration and response.

Sincerely yours,

/SIGNED/

James T. McDeavitt, M.D.
Senior Vice President
Education and Research

/SIGNED/

Herbert L. Bonkovsky, M.D.
Vice President
Research