1. NIH Proposed Use of a Central IRB (C-IRB) for NIH-funded multi-site studies Committee on Clinical Research January 26, 2015 1

2. Clinical Research Program submission of MGH faculty comments on NIH’s draft policy requiring NIH-funded multi-site clinical studies carried out in US mandated to use Central IRB (C-IRB) exceptions for site to use local IRB require justification MGH comments summarize the collective opinions of MGH clinical investigators. 2

3. Define Responsibilities of C-IRB and the Institution. Additional responsibilities delegated to IRBs over years – educate investigators about federal regulations (FDA, HIPAA, COI, etc.), – document investigator’s chief approval to conduct a study, – document approval by key ancillary department(s) – investigate allegations of misconduct. IRB primary role per federal regulations: Protecting human subjects involved in research. Suggested faculty recommendation to NIH – Final Rule present models of allocation of responsibilities to the C-IRB and those to be retained by the institution – define the entities to be held accountable for IRB and investigator infractions / misconduct 3

4. The Central IRB Business Model: Final NIH rule should clearly state – how the C-IRB will be paid for initial protocol review, continuing review, amendment review, AE/SAE reports, etc. – what, if any, administrative documentation the local IRB will be required to maintain. – the indirect costs included award are intended to cover IRB administrative costs. Currently, IRB does not charge for initial or continuing review for NIH-funded studies. 4

5. Information technology considerations: Currently, there are no specific data security protections for IRB- reviewed research. – regulations require IRB’s to determine for each study “when appropriate [that] there are adequate provisions to protect the privacy and to maintain the confidentiality of data.” Recommendation: NIH should - address a minimum standard for data protection. – offer a secure site located on an institution’s intranet where the local IRB, site investigators, and CTSA, if applicable, can access IRB-approved documents, correspondence, meeting minutes 5

6. Tracking and publishing metrics: Recommendation: NIH should track and make publically available on a published schedule metrics on all C-IRBs which reports – time to initial approval of the protocol and study documents by the central IRB; – time to approval for submission of protocol amendments and other actions for which the central IRB will be responsible; and – time to approval from the time local site PIs submit information/documents required by the central IRB, and – the methodology for data collection from C-IRBs Currently, no metrics on time to IRB approval of a protocol from submission time. 6

7. Opportunity to Acquire Important New Data Currently there is no information on AEs/SAEs reported on studies approved by C-IRBs and Academic IRBs. Final Rule provides an opportunity to assess differences in risk assessment which may exist between C-IRBs and Academic IRBs. Recommendation: - while maintaining anonymity, develop a case mix adjusted methodology for tracking injury to subjects - set standards for safety/injury reporting 7

8. Harmonizing the rule across federal agencies: Recommendation: – FDA regulations should be revised prior to mandating the use of a single IRB for multicenter studies. This would address multicenter studies sponsored by other federal agencies (DOD, AHRQ, etc.) Currently FDA regulations for device studies link the local IRB to the parent institution. 8