Overview of the Federation Model for IRB Review of the National Children’s Vanguard

Study

POctober 19, 2010

Steven Hirschfeld, MD, PhDJulia Slutsman, PhDNational Children’s Study Program OfficeEunice Kennedy Shriver National Institute of Child Health and Human Development

Overview of Presentation

• A Brief History and Background of the Federation Model

• Introduction to the National Children’s Study (NCS) Vanguard Study

• Description of Federation Model as implemented in the NCS Vanguard Study

• Status of Federation of NCS IRBs• Membership• Evaluation

• Resources for Developing a Federation IRBs • Generic Federation of IRBs Toolkit

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Brief History of the Federation Model of IRB Review

• The Federation of NCS IRBs is modeled after an approach to centralized review for multi-site studies proposed by institutions receiving Clinical and Translational Science Awards (CTSA)

• The Federated model was first presented to the Secretary's Advisory Committee on Human Research Protections (SACHRP) during its July 2009 meeting

• Federation model MOU and compact have been reviewed by OHRP

• This model of IRB review of multi-site studies will be implemented as a pilot effort with institutions participating in the NCS as well as the possibility of additional institutions with CTSA awards and NICHD networks

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What are the guiding principles for the Federated Model?

• Transparency & Communication: Determinations and documentation are shared across all reviewing IRBs

• Flexibility: Level of participation in Federation IRBs is determined by each local FWA holding institution at a given Study Location.• Tiers of participation specified in Memorandum of Understanding

(MOU)

• Coordination: The Federation is managed by the NCS Federation IRB Operations Center within the NCS Program Office• Operations center creates submission packages, FAQs, standard

operating procedures, templates

• Trust: Shared commitment to protection of NCS participants• Codified in Federation Compact

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Tiers of Participation in Federation of National Children’s Study IRBs

Tier* Review Responsibilities of Local IRB Review Responsibilities of Lead IRB

IRB of Record (NICHD or Local IRB)

MOU Required (Y or N)

1 Reliance on NICHD IRB as IRB of Record

Communication of local context issues to NICHD IRB via NCS IRB Operations Center.

Initial reviews Continuing reviews Protocol amendments initiated

by NCS Program Office Protocol amendments initiated

by local Principal Investigator**

Serious Adverse Events**

DMC (Data Monitoring Committee) reports

Unanticipated event reporting to OHRP**

NICHD Yes

2 Facilitated or full local review

Review of materials (initial reviews, amendments, continuing reviews) approved by NICHD IRB

Communication of local context issues to NICHD IRB via NCS IRB Operations Center

Local implementation review and oversight Protocol amendments initiated by local Principal

Investigator (if local IRB is IRB of record) Unanticipated event reporting to OHRP Serious Adverse Events DMC (Data Monitoring Committee) reports

Local IRB and, if desired, NICHD IRB

Yes

3 Reliance on local review

Review of materials (initial reviews, amendments, continuing reviews) approved by NICHD IRB

Local implementation review and oversight Protocol amendments initiated by local Principal

Investigator (if local IRB is IRB of record) Unanticipated event reporting to OHRP DMC (Data Monitoring Committee) reports Serious Adverse Events DMC (Data Monitoring Committee) reports

Local IRB Yes

*Adherence to principles in Compact required for all tiers; **For Tier 1 institutions only 4

IRB(s) of Record by Tier of Participation

Level of Participation

Reliance/IRB of Record

Tier 1 Reliance on NICHD IRB as the IRB of Record

Tier 2 Routine local review and option to designate

NICHD IRB as the IRB of record, in addition to the local Institution’s IRB, to allow a facilitated review

Tier 3 Local institutions IRB is the IRB of record

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Reporting of Unanticipated Events by Tier of Participation

Tier Reviewing Responsibilities Unanticipated Events

Reporting Responsibilities of Unanticipated Events to HHS and OHRP

Reporting Responsibilities of Study-Wide Unanticipated Problems to HHS and OHRP

1 Reliance on NICHD IRB as IRB of Record NICHD IRB NCS Study Director

NCS Study Director

2 Routine local review and option to designate NICHD IRB as the IRB of Record in addition to the local Institution’s IRB Local Institution Local Institution

3 Reliance on local review

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What are the advantages to an institution/IRB/investigator of participating in this model?

• The advantages of the Federation vary depending on the level of participation an institution accepts

• As a central goal of the Federation of IRBs, there will be a reduction in duplication of review and a reduction of administrative burden at the local level while maintaining the highest standard of human subject protections review and oversight

• Attention to local context is maintained and becomes the priority of the IRB. Mechanism to provide local context is set up between local institution/IRB and Operations Center

• With less responsibility to provide a duplicative review at the local level, approval turnaround is anticipated to improve

• Over time, enhanced communication and trust across disparate IRBs

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Federated IRB Participation in National Children’s Study

N=36 Study Centers Participating in National Children’s Study Vanguard Phase

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Evaluation of Performance of Federation of NCS IRBS

• Formal evaluation of the performance of the Federation of NCS IRBs will be conducted jointly by the NCS Program Office and the NICHD Office of Science Policy, Analysis & Communication

• Mixed Methods Approach: Quantitative and Qualitative methods will be used to assess membership and variation in process among tiers of participation, barriers to participation, stakeholder and member experiences with Federation

• Examples of Planned Analyses:• Perceptions of stakeholders about the value and functioning of the

Federation, barriers to participation• Length of IRB submission review cycle• Content of stipulations raised in approval letters from Federation member

IRBs

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Preliminary, Anecdotal Data from Implementation of Federation of NCS IRBs

1. Positive response from most NCS Study Center Institutions and principal investigators

2. Early adapters seems to be choosing participation in Tier 1

3. Institutions participating in NCI Studies reviewed by the NCI CIRB or Pediatric CIRB seem more comfortable with Tier 1 participation

4. AAHRPP Accreditation status is a barrier for establishing a reliance on the NICHD IRB for some but not all accredited institutions

5. Member institutions interested in knowing tiers of Participation selected by comparable institutions prior to making a decision

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Resources

• The Federation of IRBs Toolkit• Customizable materials that are required for creating and executing memorandums of understanding necessary to establish a Federation of IRBs that works collaboratively to centralize high quality human subject protections review for multi-site research protocol(s)

• Inquiries: hirschfs@mail.nih.gov

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