Central Institutional Review Board (CIRB) Initiative

1. Central Institutional Review Board (CIRB) Initiative NCRR-CTSA-NICHD Workshop on Comparing IRB Models for Multisite Pediatric Studies Jacquelyn Goldberg, JD Head, NCI CIRB Initiative goldberj@mail.nih.gov

2. Topics • Background of the CIRB Initiative • How the CIRB model works • Profile

3. The NCI CIRB Initiative - Background Established in 1999 as recommended in the Armitage Report from the NCI's Clinical Trials Program Review Group: • Help NCI create a more efficient and effective clinical research effort • Streamline or eliminate redundant processes and procedures http://deainfo.nci.nih.gov/ADVISORY/bsa/bsa_program/bsactprgmin.htm

4. The NCI CIRB Initiative Goals: • To reduce the significant local administrative burdens for multi-site trials 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

5. Adult and Pediatric Boards • Adult CIRB • Started reviewing protocols November 2001 • Menu is all adult Cooperative Group Phase 3 treatment trials • 16-18 members with adult oncology expertise • 25% patient advocates • Pediatric CIRB • Started reviewing protocols January 2004 • Menu is all COG phase 2, 3 and pilot protocols • 16-18 members with pediatric oncology expertise • 25% patient advocates

6. Selecting a CIRB Model • OHRP 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/guidance/local.htm • Model B– Central IRB review with some local IRB review • More appropriate where local IRB exists • Value of this model: LIRB provides understanding of local context • CIRB provides full Board review at no charge

7. Division of Responsibilities • CIRB and LIRB share regulatory responsibilities • The CIRB’s primary function is initial and continuing review of studies • The local institution’s primary function is consideration of local context, oversight of local performance, review of locally occurring adverse events

8. How does the NCI CIRB model work? • Institution must formally enroll • Modify FWA • Sign Authorization Agreement • Local investigator is notified of new study via • Routine Group activation announcement • CIRB semi-monthly Study Activity Update email • If the local investigator decides to open study • All the CIRB initial review documents are downloaded from the website: the completed CIRB application, the protocol, the CIRB approved consent, CIRB meeting minutes, approval letters, etc.; PI/CRA and/or the LIRB can do this

9. Contact the NCI CIRB

10. Local chair/subcommittee assesses CIRB review and decides whether to accept it or not • If accepts CIRB review - assure their local concerns are addressed (“facilitated review”) • If does not accept CIRB review – decide to review study per local procedures • Full Board does not meet; approval can occur in days • If LIRB accepts, they notify CIRB via CIRB website. • The CIRB becomes the IRB of record for that study at that site and is responsible for reviewing amendments, continuing reviews, adverse events distributed by the Group, recruitment materials, etc.

11. Consideration of Local Context • Examples • No prisoners • Assent requirement CIRB; whether and how to document LIRB • Translated consents are local • Consent template approved by CIRB; Ok for LIRB to add local boilerplate involving institutional policy and state law; Ok to tweak consent as per OHRP-Cooperative Group agreement • HIPPA • Local PI and IRB notified of all CIRB actions

12. Operations • A single contractor Operations Office supports both Boards and participating institutions and recruitment of new institutions; 2 NCI FTEs and contractor has 14 staff • Volume of protocols on Pediatric side est. 25 new protocols a year max; COG phase 2,3 and pilot • Contract close to $3 million annually; have not separated out peds costs; NCI covers cost; no fee for institutions • Pursuing AAHRPP accreditation 2009-2010

13. Total Number of Institutions Enrolled: 341 Number of Institutions using Adult CIRB only: 223 Number of Institutions using Pediatric CIRB only: 52 Number of Institutions using both Adult/Peds: 66 Estimate of Potential Pool of Institutions Enrolled Adult CIRB: 55+% of 2,000 research sites Pediatric CIRB: 63% of 189 COG institutions Number of Total Studies Available for Facilitated Review 216 Adult 136 Pediatric 80 CIRB Initiative Profile Current as of 03/31/2009

14. Facilitated Review Conducted by Institution (Pediatric Studies) Current as of 03/31/2009

15. U.S. Clinical Trials Treatment Sites vApr,2009 CTEP Total Sites = 2,097 (# of Sites that Currently have Patients Enrolled on an Open Trials) CIRB Total Sites = 341 CIRB enrolled Signatory Institutions (Adult and Pediatric) United States (AK & HI Inset) By sites

16. Challenges When began in 2001 was radical; less so 2004; less so now Managing expectations: the stakeholders who clamor for a new model may not be prepared for what that actually means Adult has 9 Groups/Peds has 1 Group Don’t underestimate complexity and therefore cost

17. Website: http://www.ncicirb.org Email: ncicirbcontact@emmes.com CIRB Toll-free Number: 888-657-3711 Fax Number: 301-560-6538 Mailing address: NCI CIRB C/O The EMMES Corporation 401 N. Washington Street, Suite 700 Rockville, MD 20850