Harvard Catalyst IRB Reliance Agreement Barbara E. Bierer, MD Director, Harvard Catalyst Regulatory Knowledge and Support Program Senior Vice President, Research, Brigham and Women’s Hospital and Sabune J. Winkler, JD Director, Harvard Catalyst Regulatory Affairs Operations Secretary’s Advisory Committee on Human Research Protections October 19, 2010

Overview Development of IRB Reliance Agreement – Initial Business Challenges – Establishing Common Principles – Elements of Reliance – Cede Review Procedures – Ongoing work

Harvard Catalyst Programs Bioinformatics Biostatistics and Research Design Community Engagement Ethics in Clinical and Translational Research Faculty Diversity and Development Health Disparities Research Novel Clinical and Translational Methodologies Participant and Clinical Interactions Resource Pediatrics Pilot and Collaborative Translational and Clinical Studies Regulatory Knowledge and Support Research Education, Training, and Career Development Translational Technologies and Resources 2

REGULATORY KNOWLEDGE AND SUPPORT Regulatory Overview Universal Gaps and Challenges Harvard Regulatory Knowledge and Support Reliance Agreement Regulatory Education Support to and Collaboration with Other Programs Research Subject Advocacy Program

18 Harvard Medical School Affiliated Entities Beth Israel Deaconess Medical Center Brigham and Women’s Hospital/Faulkner Cambridge Health Alliance Children’s Hospital Boston Dana-Farber Cancer Institute Forsyth Institute Harvard Pilgrim Health Care Hebrew SeniorLife Immune Disease Institute Joslin Diabetes Center Judge Baker Children’s Center Massachusetts Eye & Ear Infirmary Massachusetts General Hospital McLean Hospital Mount Auburn Hospital Schepens Eye Research Institute Spaulding Rehabilitation Hospital Veterans Affairs Boston Healthcare System Participating Institutions 4 Harvard University Harvard Business School Harvard Divinity School Harvard Graduate School of Design Harvard Graduate School of Education Harvard Law School Harvard School of Engineering and Applied Sciences Harvard University Health Services Kennedy School of Government Radcliffe Institute for Advanced Study Harvard Medical School Harvard School of Dental Medicine Harvard School of Public Health Harvard Catalyst Participating Institutions Boston College Connell School of Nursing Massachusetts Institute of Technology Broad Institute of MIT and Harvard Color indicates signatories of the Harvard Common Reciprocal Reliance Agreement

Striving to lower legal, regulatory and institutional barriers Consensus-driven by necessity Respectful of financial and legal independence of institutions Investigators “live in” and abide by institution rules To reduce barriers for PIs, by building on the strength of our institutions, Regulatory by necessity has a “bottom-up” approach Challenge: Creation of a centralized process in a decentralized environment, while respecting that each Harvard signatory is a separate legal entity with separate (and mostly accredited) human research protections programs

Participating Institutions – Initial Business Challenges Early Decisions: Definition of participation (all? Former GCRC entities?) Nature of authorization (one IRB? cede review? Joint review by each IRB?) Scope of review (exemptions? Clinical trials?) Definition of institutional stakeholders? (Institute Officials, FWA signatories, IRB Directors, HRPP offices, attorneys) Alignment with Harvard’s NCI-designated cancer center

Development of the Common Reliance Agreement: Early steps After identification of initial participating institutions, common agreement on: 1.Scope of agreement - Reliance agreement: common reciprocal reliance authorization (“relying institution” & “reviewing institution”) Eliminate duplicative IRB review, promote collaborative research Each has FWA 2.Agreement of ‘Jurisdiction of PI” Institution that employs overall PI has responsibility unless ceded 3.Process for request of reliance and selction process Overall PI and site PI(s) initiate requests via on line Cede Review form Determination of appropriate IRB to review (e.g. IRB expertise, complexity of Rx, liability) Notification to overall PI Authority once ceded (may withdraw for cause) and limits of authority (e.g. medical staff privileges) 4.Duties and Responsibilities to investigators, of reviewing and relying IRB Coordination Reports of amendments, adverse or unantiicpated events, protocol violations, etc Conflict of Interest review HIPAA Notification of IRB decisions, of deadlines for renewals and lapses

Development of the Common Reliance Agreement: Early steps 5. Integrate contracting offices by defining IRB Approval and Activation Agreed that IRB approval is not alone the basis for activation of the Study. Each institution could request delay of the activation of a study for any reason including the need for an executed clinical trial agreement. 6.Procedures for Managing Serious or Continuing Non-Compliance Agreed to notifications based on the timeline of discovery (ie. Discovery, Investigation, Suspension, Disapproval or Termination, Findings, etc.) Who would investigate what, and expectation of cooperation Findings and reporting Access to records and corrective actions Audits Record keeping Confidentiality 7.Subject injury and unanticipating problems Reviewing and relying IRBs obligation to report Management of injuries 8.Term and termination

Development of the Common Reliance Agreement: Early steps Further agreement upon: 1.“Uncheck the box” - Aligned federalwide assurances to ensure consistent OHRP reporting requirements 2.Align human research protection to three year renewals Aligned requirements for human research protection (ie. CITI) continuing education for re-credentialing of researchers to every three years instead of the disparate approaches ranging from annual renewal to none. 3.Agree Upon Conflict of Interest Disclosure – Zero dollar Agreed to harmonize IRB conflict of interest disclosure policies to “zero dollar” instead of the disparate conflict of interest approaches ranging from “zero dollar” to the Harvard Medical School rules and/or the federal rules. 4.Address various HIPAA status Harvard institutions are covered, hybrid and not covered. Agreed to review requirements to harmonize regulatory processes among institutions when research involves the use of Protected Health Informatio

Development of the Common Reliance Agreement – Ongoing Work 1.Expand the common IRB Reliance Agreement to additional Harvard teaching affiliates and entities 2.Harmonize Informed Consents - Subject Injury Language 3.Harmonize Informed Consents – HIPAA Authorizations 4.Common Conflict of Interest Policy for Human Research Protocols 5.Creation and adoption of electronic “cede review” form 6.Utilization of database to share “cede review” requests and info 7.SOPs: Audit, Breach, Data Security, Industry supported Clinical Trials, Subject Injury, Substantial Equivalency Process, IRB COI 8.Harmonize regulatory processes among institutions regarding regulatory interpretations by creating uniform definitions and reviews for various categories of study (discarded tissue, exempt, expedited, full board, medical record review).

Resources: Cede Review Form

Most Prevalent Reasons Cited by Investigators for Requesting Reviewing IRB: Institution of Primary Employment Patient Population Other Clinical Research Infrastructure Considerations Cede Review Form Metrics The Cede Review Form is available to all Harvard faculty to request single IRB review

Resources: Regulatory Atlas

Resources: PI Binder

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