The NCI Central IRB InitiativeThe NCI Central IRB Initiative

Jacquelyn L. Goldberg, J.D.

VA IRB Chair Training

April 8, 2004

The NCI CIRB InitiativeThe 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

BackgroundBackground

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

Board CompositionBoard Composition

One Chair and 14 Voting Members

PATIENT ADVOCATES 21% (3)

ETHICISTS 8% (1)

PHYSICIANS 43% (6)

Other Health Professionals 28% (4)

ONCOLOGY NURSES 2

PHARMACIST 1

STATISTICIAN 1

Selecting a CIRB ModelSelecting 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/guidance/local.htm

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

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.

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?

Division of Responsibilities 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

How does the NCI CIRB How does the NCI CIRB model work?model work?

CIRB approves protocolLocal investigator is notified of

protocol via– Routine Group activation

announcement– CIRB e-mail

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

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.

Adverse Event ReportingAdverse 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

Informed ConsentInformed 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.

Current Status of InitiativeCurrent Status of Initiative

Number of Participating LIRBSTarget of 100 LIRBs159 LIRBs have joinedRepresents 254 research sites

(potential of 1500-2000)

Use of Facilitated Review101 of the 159 LIRBs have used

facilitated review at least onceEstimated 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

NCI goal for 2003 to show use of facilitated review in 70-80 LIRBs

NCI goal for 2004 is expansion to 500 sites

Evaluation PlanEvaluation 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

Benefits to InvestigatorsBenefits to InvestigatorsNo advance preparation for IRB review at

the local site– no IRB application to complete, just download the IRB

packet from the CIRB websiteNo 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

6 Easy Steps6 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

www.ncicirb.org