0. Developing the 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
CTSA Champions of Change
June 22, 2009

1. Overview Whirlwind overview of Harvard Catalyst
Connections
Enabling research At the cutting edge of discovery
Nurturing C/T investigators
Development of IRB Reliance Agreement
Initial Business Challenges
Establishing Common Principles
Elements of Reliance
Ongoing work
Talking Points: Overview will be a quick introduction to Harvard Catalyst and then a deeper focus on the story of the Harvard Catalyst IRB reliance agreement

2. Cambridge Health Alliance
Harvard School of Public Health
Harvard School of Dental Medicine
Harvard Medical School
Radcliff Institute for Advanced Study
Beth Israel Deaconess Medical Center
Brigham and Women’s Hospital
Kennedy School of Government
Children’s Hospital
Harvard University Health Services
Dana Farber Cancer Institute
Harvard School of Engineering and Applied Sciences
Forsyth Institute
Harvard Law School
Harvard Graduate School of Education
Harvard Graduate School of Design
Immune Disease Institute
Joslin
Harvard Divinity School
Judge Baker Children’s Center
Harvard Business School
Massachusetts Eye and Ear Infirmary
Harvard University
Massachusetts General Hospital
Broad Institute of MIT and Harvard
MIT
McLean Hospital
Boston College Connell School of Nursing
Schepens Eye Research Institute
Mount Auburn Hospital
Veteran Affairs
Boston Healthcare
System
Spaulding
Rehabilitation Hospital

3. 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
Harvard Catalyst comprises 13 programs, each addressing a key component of translational research, from accessing and assessing data to designing trials, developing new technologies to clinical education, addressing regulatory requirements to understanding community needs.

4. Participating Institutions
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
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
Talking points: The IRB Reliance Agreement has 9 signatories representing 20 entities. Harvard Catalyst touches nearly every part of Harvard engaged in biomedical research. We are a shared enterprise between Harvard University, its 10 schools, 18 Academic Health Centers, and numerous other community and healthcare partners as well. Our resources are available to all investigators with a Harvard faculty appointment, regardless of their institutional affiliation.

5. Participating Institutions – Initial Business Challenges
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
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
Talking points: The complex decentralized regulatory environment of C/T research remains a challenge as Harvard and the Harvard-affiliated hospitals are legally and financially distinct entities, each individually responsible for contractual and regulatory aspects of research. The existence of multiple, legally independent institutions within the Harvard system continues to add a layer of complexity, often multiplying the institutional policy requirements and require navigating multiple IRBs, multiple grants and contract offices and management.

6. Development of the Common Reliance Agreement: Early steps
After identification of initial participating institutions, common agreement on:
Scope of agreement -
Reliance agreement: common reciprocal reliance authorization (“relying institution” & “reviewing institution”)
Eliminate duplicative IRB review, promote collaborative research
Each has FWA
Agreement of ‘Jurisdiction of PI”
Institution that employs overall PI has responsibility unless ceded
Process for request of reliance and selction process
Overall PI and site PI(s) initiate requests via on line Cede Review form (in development)
Determination of appropriate IRB to review (e.g. IRB expertise, patient number or complexity of Rx, liability)
Notification to overall PI
Authority once ceded (may withdraw for cause) and limits of authority (e.g. medical staff privileges)
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
Policy compliance responsibility
Sponsored research agreements and contracting

7. 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
Subject injury and unanticipating problems
Reviewing and relying IRBs obligation to report
Management of injuries
8. Term and termination

8. Development of the Common Reliance Agreement: Early steps
Further agreement upon:
“Uncheck the box” -
Aligned federalwide assurances to ensure consistent OHRP reporting requirements
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.
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.
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

9. Development of the Common Reliance Agreement – Ongoing Work
Common Reliance Agreement was fully executed on March 31, 2009 and the work continues:
Expand the common IRB Reliance Agreement to additional Harvard teaching affiliates and entities
Harmonize Informed Consents - Subject Injury Language
Harmonize Informed Consents – HIPAA Authorizations
Draft Conflict of Interest Policy
Create electronic “cede review” form
Create of database to share “cede review” requests and info
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).

10.
More information on all of our resources and programs is available at the Harvard Catalyst website….catalyst.harvard.edu