James T. McDeavitt, M.D.
Senior Vice President
Education and Research
Carolinas Medical Center
Carolinas HealthCare System
P.O. Box 32861
Charlotte, North Carolina 28232-2861
Dear Dr. McDeavitt:
My thanks to you and Dr. Herbert Bonkovsky for your April 13 letter. As your letter noted, the Food and Drug Administration’s March 2006 guidance document, Using a Centralized IRB Review Process in Multicenter Clinical Trials, states that “The Agency hopes that sponsors, institutions, institutional review boards (IRB), and clinical investigators involved in multicenter clinical research will consider the use of a single central IRB (centralized IRB review process), especially if using centralized review could improve the efficiency of IRB review.” I want to assure you that the Office for Human Research Protections fully agrees with FDA’s position on the benefits of relying on a single central IRB for multicenter research.
In fact, the advance notice of proposed rulemaking (ANPRM) on IRB accountability that OHRP issued on March 5, 2009, was proposed precisely to address this issue. As you indicated in your letter, concerns about regulatory liability under the Department of Health and Human Services human subject protection regulations appear to be one of the main reasons inhibiting institutions from exercising the regulatory flexibility that currently permits institutions to rely on the review of an IRB operated by another institution or organization. The ANPRM sought public comment on whether OHRP should pursue a notice of proposed rulemaking to enable OHRP to hold IRBs and the institutions or organizations operating the IRBs directly accountable for meeting certain regulatory requirements of the HHS regulations for the protection of human subjects. You can view the Federal Register notice. The majority of public comments we received supported this regulatory change, and we are continuing to consider whether to pursue this change in order to further encourage institutions to rely on IRBs that are operated by another institution or organization, when appropriate.
However, even in the absence of new regulation, OHRP is taking steps to address institutions’ concerns about relying on an IRB external to the institution. For example, as you indicated, we have archived prior guidance documents that suggested OHRP favors local IRB review over review by a non-local IRB, a position that OHRP no longer holds. (The reviewing IRB should nonetheless have appropriate knowledge of the local context.) Also, in our recent compliance evaluations, we have taken into consideration whether a single central IRB external to the
institution was responsible for any identified regulatory noncompliance with 45 CFR part 46. In cases where an external central IRB is found to be responsible for any identified regulatory noncompliance with 45 CFR part 46, we will continue to clearly indicate this in our compliance determination letters and will communicate directly with the external IRB as appropriate. An example of how OHRP addresses this issue can be found in a recent compliance determination letter, section A(2) [PDF - 58 KB] regarding the discussion of corrective actions.
Again, thank you for asking for clarification about this important issue. I have sent an identical response to Dr. Bonkovsky.
Jerry Menikoff, M.D., J.D.
Office for Human Research Protections
cc: Dr. Joanne Less, FDA