Cooperative IRB Review Arrangements for Multicenter Research: Central IRB Perspective

1. Cooperative IRB Review Arrangements for Multicenter Research: Central IRB Perspective Workshop on Challenges in the Review of Pediatric Research for Institutional Review Boards (IRBs) Felix Khin-Maung-Gyi, PharmD, MBA, CIP, RAC CEO Chesapeake Research Review, Inc. NIH CTSA Web Conference September 11, 2007 Bethesda, MD

2. Agenda • Overview of CRRI IRB • Challenges in reviewing pediatric research • Potential solutions • Questions

3. Types of IRBs • Academic Medical Centers • Community Hospital • Government Agency • Associations/Advocacy Groups • Independent • “Central”

4. Regulations Governing IRB Activities • 45 CFR 46 – NIH/PHS/HHS • 21 CFR 50 & 56 – FDA • ICH Guidelines (E6) • Common Rule • 21 CFR 11 – FDA • (? IRB Involvement with 21 CFR 54?) • HIPAA

5. CRRI’s IRB • Academic medical center based model • Primary reviewer system to lead protocol and investigator discussion of reviews • Reviews full range of research (45 CFR 46; 21 CFR) • Experience includes with sponsors, CROs; as investigators; and on institutional IRBs • Clinical/non-clinical scientists, Ethicists, Lay Members • In-house, non-staff/consultant IRB designee

6. CRRI’s IRB • Multiple weekly meetings: 3 Panels of 7 Members • Three pediatricians; one pediatric nurse • practitioner (as well as PhD neuroscientist) • Specialty Consultants called on as needed • Strong non-scientist representation • Key IRB staff attend IRB meetings • Members attend; Alternates PRN • Team support of all IRB meetings/members

7. CRRI’s IRB • One integrated IRB Administrative Support • Routine training sessions (for both staff and IRB) • Staff to IRB Member ratio: > 2:1 • Sub-Committee: SAEs & Safety Reports • IRB Executive Committee (IEC, policy setting) • External Conflict of Interest Committee • Internal IRB Member Performance Evaluation • Subcommittee of IEC

8. Reporting Responsibilities PI/SITE IRB REGULATIONS SPONSOR / REPRESENTATIVE

9. Human Subject Protection Regulations Nuremberg Code Declaration of Helsinki BELMONT PRINCIPLES

10. Belmont Report April 18, 1979 • Basic Ethical Principles • Respect for Persons  Consent/Assent • Beneficence  Risk:Benefit (46.407/56.54) • Justice  Subject Selection www.hhs.gov/ohrp/humansubjects/guidance/belmont.htm

11. Challenges for CRRI IRB in Reviewing Pediatric Research • Poor protocol design • Determination of “risk” category • Therapeutic Misconception • Poor site selection/Training • Variable execution and implementation/SOP • Investigator/Institutional Over-delegation • Lack of Institutional “will” • Confusion regarding “who’s in charge” • Poor patient/public understanding of research

12. Ethical Concerns • Conflicts of interests (interest of subject vs. interest of PI/institution) • Autonomy (e.g., assent and age of majority) • Coercion (e.g., subject recruitment/payment) • Privacy/confidentiality (e.g. genetics research)

13. “These are the regulations…”

14. “…and these are the interpretations.”

15. How CRRI Addresses Issues • Escalating Review Process • Non-binding review • Staff review at intake • Regulatory review as necessary • Designee review (may be binding) • Full-board review (multiple options) • Executive/IO Action • Staff/IRB training and corrective actions • Policy Review/Modification • Ongoing QA/AC Activity

16. How CRRI Addresses Issues • AAHRPP Accreditation Standardized/Documented Approach • Implementation of new technology “smart form” • Assume collaborative responsibility/authority • Workflow processes for institutional partners “shared responsibilities for HRP”

17. HSP HSP HSP HSP HSP Agencies Agencies IRB Better Medicines for Patients A Better Approach High Quality Data Subjects Research Settings & PI Sponsor CRO Sponsor The Partnership for Human Subject Protection