Overview of the Federation Model for IRB Review of the National Children’s Vanguard Study P October 19, 2010 Steven Hirschfeld, MD, PhD Julia Slutsman, PhD National Children’s Study Program Office Eunice 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

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

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

Tiers of Participation in Federation of National Children’s Study IRBs 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 Local IRB and, if desired, NICHD IRB 3 Reliance on local review Local IRB NIH Eunice K. Shriver National Institute of Children’s Health and Development (NICHD) intramural IRB is lead IRB for Tier 1 *Adherence to principles in Compact required for all tiers; **For Tier 1 institutions only

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

Reporting of Unanticipated Events by Tier of Participation 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 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 3 Reliance on local review

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

Federated IRB Participation in National Children’s Study Additional Membership from Study Location Hospitals, Birth Centers and Contract Research Organizations is Expected Please note that numbers include institutions that have either submitted signed MOUs or are in the process of submitting MOUs and have indicated their Tier of planned participation with some certainty N=36 Study Centers Participating in National Children’s Study Vanguard Phase

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

Preliminary, Anecdotal Data from Implementation of Federation of NCS IRBs Positive response from most NCS Study Center Institutions and principal investigators Early adapters seems to be choosing participation in Tier 1 Institutions participating in NCI Studies reviewed by the NCI CIRB or Pediatric CIRB seem more comfortable with Tier 1 participation AAHRPP Accreditation status is a barrier for establishing a reliance on the NICHD IRB for some but not all accredited institutions Member institutions interested in knowing tiers of Participation selected by comparable institutions prior to making a decision

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