1. Columbia University IRB IRB 101 September 21, 2005 George Gasparis, Executive Director, CU IRB Asst. V.P. and Sr. Asst. Dean for Research Ethics

2. September 21, 2005Page 2 Objectives This session will provide information on: Submission of modifications/amendments to the IRB IRB review of modifications Submission of unanticipated problems involving risks/adverse events to the IRB IRB review of adverse events – IRB oversight monitoring of risks

3. September 21, 2005Page 3 All Human Research at Columbia University Governed by Ethical Principles and the Requirements of HHS and FDA Regulations and NY State Law

4. September 21, 2005Page 4 Declaration of Helsinki, 1964 -Provides ethical principles for human research with emphasis on clinical research -Developed by the World Medical Assembly -Has undergone 8 revisions; the most recent in October 2000 with clarification posted in 2002

5. September 21, 2005Page 5 Declaration of Helsinki, 2002 -Article 16: Physicians should abstain from…research…unless they are confident that the risks…have been adequately assessed and… satisfactorily managed. Physicians should cease any investigation if the risks are found to outweigh potential benefits or if there is conclusive proof of positive and beneficial results.

6. September 21, 2005Page 6 Declaration of Helsinki, 2002 -Article 13: The researcher has the obligation to provide monitoring information to the committee, for review, information regarding funding, sponsors, institutional affiliations, other potential conflicts of interest and incentives for subjects.

7. September 21, 2005Page 7 DEPARTMENT OF HEALTH & HUMAN SERVICES

8. September 21, 2005Page 8 Federal Regulations for the Protection of Subjects from Research Risks 45 CFR Part 46 1981

9. September 21, 2005Page 9 45 CFR 46.103(b)(4) Written procedures which the IRB will follow: (iii) for ensuring prompt reporting to the IRB of proposed changes in a research activity, and for ensuring that such changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval except when necessary to eliminate apparent immediate hazards to the subject.

10. September 21, 2005Page 10 CUMC IRB Approval Letter “Any proposed changes in the protocol must be immediately submitted to the IRB for review and approval prior to implementation, unless such a change is necessary to avoid immediate harm to the participants. Additionally, any serious and unexpected adverse events or other problems that involve risks to subjects must be reported to the IRB in accordance with the CUMC IRB AE Reporting Policy, dated April 13, 2004. All submissions for modifications and adverse events must be submitted through RASCAL.”

11. September 21, 2005Page 11 45 CFR 46.109(a) An IRB shall review and have authority to approve, require modifications in (to secure approval) or disapprove all research activities covered by this policy.

12. September 21, 2005Page 12 As a result modifications may arise from: 1)A request from the IRB as a stipulation for approval. -these are handled in RASCAL within the submission of the new protocol or continuing review as “returns” to the investigator, if done prior approval. IRB does not call these “modifications”, unless they occur after approval. ______________________ 2)A request from the sponsor or “lead Principal Investigator (PI)” when collaborating with other sites. 3)At the discretion of the Columbia PI (e.g., modifying the research procedures, change in research personnel; change in funding source). -items 2 and 3 are handled in RASCAL as a new submission, called a “modification”.

13. September 21, 2005Page 13 IRB Review of Modifications/AEs 1)Expedited Review – “minor changes in previously approved research during the period (of one year or less) for which approval is authorized” OR adverse events that are not believed serious, unanticipated, and related to the study intervention. OR 2) Full Committee Review – all other modifications or serious and unanticipated adverse events

14. September 21, 2005Page 14 Considerations for Modifications 1)Change in Funding Source: -attach complete grant or contract application; -summarize changes in research as a result of grant; -if multicenter and Columbia is the prime awardee: -summarize what each site will do. 2)Changes in Research Personnel: -change in research staff should not only be summarized in the modification, BUT ALSO added in the Personnel Section; ensure that each new “key personnel” member has completed GCP and HIPAA training.

15. September 21, 2005Page 15 Considerations for Modifications 3)If the modification affects the information in the informed consent document OR the subject should be notified of new information that may affect their decision to participate, ensure that the consent form is appropriate revised; mention in the Modification Summary that the consent has been revised accordingly. 4)If consent forms are revised and the submission includes both a RASCAL generated consent form and one attached in RASCAL, explain how the forms are different. If not different, archive the one that is attached in RASCAL, so that the RASCAL generated consent will be the final approved form(s).

16. September 21, 2005Page 16 Considerations for Modifications 3)Ensure that Outdated Attached Documents are Archived in RASCAL 4)Ensure that Attached Documents are clearly and consistently labeled (e.g., “ICF 04022004” for the form attached in 2004 and “Adult consent form 04012005” for the one attached in 2005). -This will eliminate the need for the IRB and research staff to open all/several attachments to identify whether a document was previously attached and not revised, previously attached and revised or a new document will increase efficiency and turnaround time.

17. September 21, 2005Page 17 Considerations for Modifications 5)If the Version Date of the protocol is included in the title or in the Protocol Version Field, ensure to update the information when a modification includes a revised protocol. 6)Ensure that the Modification Summary and the Attached Documents are consistent. - (e.g., Modification Summary states “Spanish consent forms” but the attachments include the Spanish consent forms and a DSMB report)

18. September 21, 2005Page 18 Considerations for Adverse Event Reports Adverse Events and Unanticipated Problems involving risks to Subjects should be submitted either Promptly or at Continuing Review in accordance with the Columbia Adverse Event Reporting Policy (April 13, 2004)

19. September 21, 2005Page 19 Considerations for Adverse Event Reports If the events meet the criteria for prompt reporting, submit the Information using the Adverse Event Report module in RASCAL. All other events should be summarized in a separate report and attached in the submission for Continuing Review