1. New IRB Guideline Changes and Converting to eIRB - Suggestions for Maintaining Compliance. Ramesh Ghodgaonkar, BPHARM, MSITS, MSB, MBA Betsy Johnson, BA Frederick W. Luthardt, MA, MA, CCRP Barbara L. Starklauf, MAS, CIP The Office of Human Subjects Research’s Compliance Monitoring Program Educational Seminars: November 3, 2010 JHBMC Carroll Auditorium November 10, 2010 BRB G-01

2. Session Objectives Give updates about the Monitoring Program Highlight recent IRB guideline announcements Provide recommendations and tips to maintain compliance Discuss why “Compliance Matters” Engage in open Q & A

3. What’s been happening in the Compliance Monitoring Program? Introducing our new Monitor: Betsy Johnson Our pre-enrollment visits for investigator-held IND/IDE studies are increasing, especially in the last 6 months! New SOPs added to the Researcher’s Tool Kit http://www.hopkinsmedicine.org/institutional_review_board/about/compliance_monitoring/research ers_tool_kit/index.html http://www.hopkinsmedicine.org/institutional_review_board/about/compliance_monitoring/research ers_tool_kit/index.html Monitoring focus on new investigators and changing monitoring trends Clinicaltrials.gov registration and Compliance Worksheet, FDA Form 3674 requirements

4. Recent Communiqués Dr. Dan Ford, Vice Dean for Clinical Investigation, issued two announcements of interest to investigators: – March 23, 2010 regarding study-team members and changes in research – October 15, 2010 regarding the transition requirement for “paper studies” to eIRB The first announcement has its roots in recent compliance findings The second is the follow-up to the September notice

5. Announcement #1: Research Personnel “All study team members who conduct human subjects research must be listed on the IRB application…” When adding or deleting a study team member, “Only when the change in research is approved by the IRB may they start to participate in the research.”

6. Compliance Suggestions eIRB Study Team roster Keep track of study team member status and record any changes using a Responsibility Log …

7. Announcement #1: Changes in Research “…all changes in IRB approved research must be reviewed and approved by the IRB before the changes may be implemented.” “The only exception to this requirement is that an emergency change may be made without prior IRB review and approval.” “Emergency changes to eliminated a hazard to a subject must be reported promptly to the IRB for review.”

8. Compliance Suggestions eIRB Change in Research Tracking To keep in compliance, the PI must assure that… Spontaneous protocol deviations must be reported to the IRB, at least annually Planned deviations must be reported to the IRB as a Change in Research, which must be IRB approved Exceptions or Exemptions (e.g., to an inclusion/exclusion criterion) must be reported to the IRB as a Change in Research That an emergent Change in Research is fully documented

9. Announcement #2: The eIRB Conversion All “paper studies” (those with an “RPN” application number) must be converted before January 1, 2011. “JHM IRB will stop accepting paper continuing reviews of changes in research on Jan. 1, 2011.” “For studies that are still enrolling or in follow-up, you will need to complete the full [eIRB] application.”

10. Tips for the eIRB Conversion Do not make any changes to the protocol (which includes changes to the study team roster) Mark “no” for question 7.0 in section 1 and “yes” for question 8.0 Add the “paper study” number (RPN#) for question 9.0 and upload a progress report using the form supplied in eIRB in section 10.0 Upload all applicable study documents in MS- Word, which allows for IRB staff to make changes, if necessary.

11. Major Compliance Differences in eIRB: Improvements that can help eliminate historical compliance problems Informed consent forms receive the IRB approval logo on each page, and barring changes to the consent and/or protocol, the consent does not expire. Deviations, Events, and Unanticipated Problems are reported via eIRB (i.e., the paper forms are not to be submitted) All hard-copy documentation is to be scanned and uploaded to eIRB Communication with the IRB for protocol issues

12. Compliance considerations for the eIRB conversion Take the opportunity to review any compliance problems in the past, so as not to continue problems in the future: – Documenting informed consent – Assuring subject eligibility – Reporting deviations, changes in research, protocol events or problems – Study personnel roster is up to date and study team members are trained, etc.

13. Compliance Matters New and revised guidelines can emerge from common compliance problems identified by the monitoring team Repeated instances of non-compliance, observed serious disregard for research regulations and requirements, or sentinel events, may trigger an audit. The Vice Dean for Clinical Investigation or the IRB can order an audit…

14. Audits and their ramifications… Internal audits, which are qualified as either “for-cause” or “directed,” require the monitoring team to investigate the reported or discovered areas of serious non-compliance In some cases, depending on the nature of the protocol (NIH funded, under FDA IND/IDE authority, etc.), the Vice Dean must report the audit findings to – The Office of Human Research Protection (OHRP) at the Department of Health and Human Services – The US Food and Drug Administration (FDA) The DHHS has the authority to initiate audits and FDA to conduct inspection FDA inspection findings (e.g., FDA 483 Warning Letters) are posted to the FDA website and are part of the public domain In some cases, Institutional disciplinary action may be taken.

15. How to contact us The monitors may be contacted at the OHSR office at 410-955-3008 for questions and assistance. Reed Hall, Suite B-130 – The monitors may also be contacted directly by email: – rghodga1@jhmi.edu rghodga1@jhmi.edu – fluthar1@jhmi.edu fluthar1@jhmi.edu – ejohns95@jhmi.edu ejohns95@jhmi.edu – Regulatory questions concerning recordkeeping requirements may be directed to: Regulatory Affairs Specialists or the Assistant Dean for Human Subjects Research Compliance.