1. The NCI Central IRB Initiative Jacquelyn L. Goldberg, J.D. VA IRB Chair Training April 8, 2004

2. The NCI CIRB Initiative Purpose: To establish a Central IRB for NCI Phase 3 multi-center trials – To eliminate the significant administrative burdens on local investigators and IRBs while maintaining a high level of human subjects protection – To enhance the protection of research participants by providing consistent expert IRB review at the national level before the protocol is distributed to local investigators

3. Background Armitage Report NCI holds an FWA NCI Director appoints diverse Board Meeting monthly since January 2001 Menu includes all Phase 3 Adult Cooperative Group protocols (20-30 new per year), some Phase 2, plans for peds Daily administrative operations managed by contractor

4. Board Composition One Chair and 14 Voting Members PATIENT ADVOCATES21% (3) ETHICISTS 8% (1) PHYSICIANS43% (6) Other Health Professionals28% (4) ONCOLOGY NURSES 2 PHARMACIST 1 STATISTICIAN 1

5. Selecting a CIRB Model OHRP (OPRR) allows for different centralized IRB models See Guidance of August 27, 1998 (updated July 21, 2000) entitled “Knowledge of Local Research Context” http://ohrp.osophs.dhhs.gov/humansubjects/guid ance/local.htm http://ohrp.osophs.dhhs.gov/humansubjects/guid ance/local.htm

6. Model A– Central IRB review only – Appropriate where no local IRB exists – Understanding of local context obtained via site visits, audits, teleconferences – Large expenditure in time and money to understand local context

7. Model B– Central IRB review with some local IRB review – More appropriate where local IRB already present – Value of this model: Can utilize LIRB for understanding of local context and forego expense of site visits, etc.

8. NCI chose Model B for practical reasons – Unlike many other CIRBs, the NCI CIRB does not exist in lieu of a local IRB – Local IRBs already exist and NCI must interface with them – Who better to understand local research context than local IRB chair/members?

9. Division of Responsibilities CIRB and LIRB share regulatory responsibilities The CIRB’s primary function is initial and continuing review of protocols The local institution’s primary function is consideration of local context and oversight of local performance

10. How does the NCI CIRB model work? CIRB approves protocol Local investigator is notified of protocol via – Routine Group activation announcement – CIRB e-mail

11. If the local investigator decides to open protocol, – OPTION 1: Investigator or CRA downloads the completed IRB application, protocol and consent from the CIRB website and submits documents to local IRB; LIRB downloads remaining documents – OPTION 2: PI/CRA downloads all the documents and submits them to the LIRB

12. Local IRB chair or a subcommittee reviews for local concerns and decides whether to approve (“facilitated review”) If LIRB accepts, they notify CIRB. The CIRB becomes the IRB of record. It handles amendments, continuing reviews, adverse events etc. If LIRB does not accept, LIRB can decide to review the protocol themselves as per their own local procedures.

13. Adverse Event Reporting Local site/PI does not report AEs to CIRB (local PI must still report local event to LIRB) CIRB accesses NCI’s adverse event reporting system – CIRB notified of AEs reported to FDA CIRB decisions posted on Web for local IRB use

14. Informed Consent Local boilerplate additions to the informed consent dealing with state and local law, institutional requirements, or IRB policies Minor word changes which do not alter the meaning of the CIRB approved contents Revisions/changes to the local consent form other than those described above require local full board review and facilitated review may not be used.

15. Current Status of Initiative Number of Participating LIRBS Target of 100 LIRBs 159 LIRBs have joined Represents 254 research sites (potential of 1500-2000)

16. Use of Facilitated Review 101 of the 159 LIRBs have used facilitated review at least once Estimated lag time of six months between joining and first facilitated review – High turnover of IRB coordinators – Attention elsewhere (HIPAA) – Not yet developed internal SOPs – IRB culture

17. NCI goal for 2003 to show use of facilitated review in 70-80 LIRBs NCI goal for 2004 is expansion to 500 sites

18. Evaluation Plan Measure local utilization of facilitated review Quantify CIRB effect on local site time frames Assess the CIRB experience: – Local IRB Chair – LIRB Coordinator – Site Principal Investigator for protocol – CIRB members Evaluate the quality of CIRB reviews Demonstrate CIRB compliance with federal regulations

19. Benefits to Investigators No advance preparation for IRB review at the local site – no IRB application to complete, just download the IRB packet from the CIRB website No waiting for the next meeting of the full board – investigators can enroll patients in trials much faster potentially as quickly as 24-48 hours – greater menu of clinical trials available to patients – improves patient access to NCI sponsored trials No need to submit continuing reviews, amendments or AE reports (except for AEs at local site) to the LIRB or the CIRB - CIRB becomes IRB of record

20. 6 Easy Steps Modify institution’s FWA to include the CIRB Sign authorization agreement Create a local IRB SOP for utilizing the CIRB – Determine the composition of the LIRB subcommittee that will conduct facilitated review Notify local investigators of the new process Copy the CIRB office on the notification (which will show that the process is complete) Provide CIRB office with LIRB and PI site contact information

21. www.ncicirb.org