“OHRS Submit” to “Activation”: Where does the paperwork go and what are the common hold ups in review/activation?

1. “OHRS Submit” to “Activation”:Where does the paperwork go and what are the common hold ups in review/activation? Amanda Hammond, JDDeputy Director Emily EldhAssistant Director for Clinical Research Sara Harnish, JDAssistant Director for Non-Clinical Research

2. Overview • Background on OHRS • Triage, review, approval and activation path for: • New Protocols • Amendments • Continuing Reviews • Pitfalls that slow the time to Approval and Activation

3. OHRS

4. OHRS Organization

5. OHRS Tracks and Processes…

6. OHRS Tracks and Processes… In 2008 OHRS Received ~ 8,650 Submissions (not including IND Safety Reports) ~ 26,500 Documents

7. Coordinate Boards and Activation Agents • At least 194 meetings each year • 4 scientific review committees • 6 institutional review boards • Coordinate Routing for Activation at: • BIDMC / BWH / CHB / DFCI / MGH • Nursing / Pharmacy / Rad Safety / BioSafety / QACT / Research Admin / CRL / CMCF / etc.

8. Intake & Triage

9. Intake and Triage:New Protocols • When New Protocol Application is Complete: • Route “preview” copies to: • Research Administration and Clinical Trials Billing/Budget Offices at participating institutions • Multicenter Coordinating Committee, if PI-initiated Multicenter study • Tumor Imaging Metrics Core, if applicable • Cell Manipulations Core Facility, if applicable • Radiation Safety Officers at participating institutions • Save electronic versions in OHRS Shared File area

10. Intake and Triage:New Protocols • When New Protocol Application is Complete: • Triage for P/SRC & IRB review: • SRC vs. PSRC • Expedited vs. Full P/SRC • IRB A/B vs. IRB D • Expedited vs. Full IRB • Schedule for SRC/IRB meetings, as applicable • Enter into ReX (which is the OHRS protocol database) • Enter into new protocol tracking sheet • Send notice to study primary contact and PI advising of SRC/IRB review path and meeting dates, if applicable

11. Intake and Triage:Sample Intake Checklist for New Protocols

12. Intake and Triage:New Protocols • Problem Spots • Missing required documents • Wrong application form was used • Incomplete forms • Inconsistent information provided on forms

13. Intake and Triage:New Protocols • New Project Applications: • Clinical Trials • Social/Behavioral Research • Medical Record Reviews • Use of Specimens • Request for Exemption or Determination that Research is Not Human Subject Research

14. Required documents Endorsement Form Front Sheet Application Form Staff Signature Pages Protocol Consent Form or Request for Waiver Priority List Electronic Copy Also submit if applicable: Radiation Safety Screening Form Subject/Pill Diary Questionnaires Recruitment Material Grant application Alert Page Investigator’s Brochure Lab Manual Intake and Triage:New Protocols

15. Intake and Triage:New Protocols • Assigned to HRC Team Lead based on: • Clinical Trial vs. Non-Clinical Trial • Disease/Discipline Program

16. HRC Team Assignments

17. Intake and Triage:Amendments • Download from OHRS Submit by saving to OHRS Shared File • Print all associated documents • Problem Spots • Make sure all supporting documents are submitted • If you reference adding study team members in your “general amendment form,” please post your study team update form with the general amendment

18. Intake and Triage:Amendments • Considerations for triaging for SRC/IRB Review: • Nature of changes, e.g. scientific, etc. • Minor vs. Major changes • Expedited vs. Full Review • Activation Agents • Sign-off required vs. Notification

19. Intake and Triage:Amendments • Once triaged: • Schedule in ReX • Enter into Tracking Sheet • Send notice of review path and meeting dates to primary contact and PI • Except for dose escalation/cohort changes, study team updates and add sites • Route to assigned HRC

20. Intake and Triage:Continuing Reviews • Download from OHRS Submit by saving to OHRS Shared File • Print all associated documents • Problem Spots • Make sure all supporting documents are submitted

21. Intake and Triage:Continuing Review • Pull relevant history for IRB review from ReX, OncPro & QACT: • Protocol Summary Report • Deviation Report • Current version of Consent • Prior minutes • Accrual data from QACT

22. Intake and Triage:Continuing Review • Expedited vs. Full Board Review • Eligible for expedited IRB review if meet categories set out in OHRP/FDA List: • Minimal Risk and was originally determined to meet criteria in one of Categories 1 – 7, or • Greater than Minimal Risk but: • Research is permanently closed to enrollment andall subjects have completed all research-related interventions andactive for long-term follow-up only, OR • No subjects have been enrolled locally and no additional risk identified anywhere, OR • Research is active for data analysis only

23. Intake and TriageCRs • Typically expedited if check: • Box 1 * • Box 2 * • Box 5 ** • Box 6 • Box 7 • Typically full board if check: • Box 3 • Box 4 * Note: may require full board review if additional risks identified at other sites ** Note: may require full board review if not permanently closed to enrollment

24. OHRS Pre-Reviews & Board Reviews

25. HRC Pre-Review & Board ReviewsNew Protocols • OHRS Pre-Review • Consistency among forms • Identify missing information • Focus on consent form • Goal is to lessen conditions for IRB approval • Anticipating IRB conditions based on discussions at previous IRB meetings

26. HRC Pre-Review & Board ReviewsNew Protocols

27. HRC Pre-Review & Board ReviewsNew Protocols • OHRS consent form comments: • Suggestions and not required • Based on comments made by IRB at meetings • OHRS comments are forwarded to IRB for consideration

28. HRC Pre-Review & Board ReviewsNew Protocols • Problem spots • Poorly formatted informed consent documents • Language is too technical • Consents are not consistent with protocol • Potentially exculpatory language included • Consent Template is being updated • Standard language for procedures • Reflect recent IRB preferences

29. HRC Pre-Review & Board ReviewsNew Protocols • IRB meeting date is tentatively scheduled 4 weeks from SRC review date • OHRS tries to get SRC minutes ASAP • Provide three meeting dates with submission due dates • Meeting Preparation – at least 1.5 weeks before meeting • Organize all protocol paperwork • Identify and confirm reviewers • Packets need to be printed, collated and posted electronically • Packets delivered/distributed at least 1 week prior to meeting

30. HRC Pre-Review & Board ReviewsNew Protocols • Problem spots • Responses that include changes beyond the scope of SRC or IRB conditions • Requires submission of an Amendment • Late “Add Site” Amendments • May cause delay in activation and need for subsequent amendment if activation agents require changes to IRB approved documents

31. HRC Pre-Review & Board ReviewsAmendments • Dose Escalations/Cohort Change – High Priority • If consistent with protocol, then routed for expedited IRB review • If changes the protocol, then may require full board review • Opening next study Phase – High Priority • Scheduled for earliest full board – typically Tuesday IRB

32. HRC Pre-Review & Board ReviewsAmendments • Regular Amendment affecting Safety – High Priority • Scheduled for earliest full board meeting • Protocol status may be updated prior to meeting • CTEP Amendments – Priority • Must be reviewed with 90 days • IDB Updates • Routed for expedited review

33. HRC Pre-Review & Board ReviewsAmendments • Regular Amendments • Minor changes may be eligible for expedited review • Major changes may require SRC review • Change from single center study to multicenter study requires MCC review prior to IRB review • Study Team Updates • Routed for expedited review • Add Sites • Routed for expedited review

34. HRC Pre-Review & Board ReviewsAmendments • Problem Spots • Justification does not provide enough information • Supporting documentation is not included

35. HRC Pre-Review & Board ReviewsContinuing Review • Expedited Continuing Reviews • If medical review required, routed to medical reviewer room • Given volume of submissions, currently reviewed in order of expiration date • Full Board Continuing Reviews • Attempting to schedule for review in real time (i.e., as close to submission date as possible)

36. HRC Pre-Review & Board ReviewsContinuing Reviews • Problem Spots • Continuing review submitted close to expiration date • Form is not complete or includes inconsistent information

37. HRC Pre-Review & Board ReviewConditions and Approvals • Once responses to conditions are submitted: • HRC reviews to confirm responses are complete and address committee concerns • Verification Record is created and routed to an IRB member for review and approval • Approval memo is generated • ReX is updated • Tracking Sheet, if applicable, is updated • Material is forwarded to the OnLine Team and Activation Coordinators

38. HRC Pre-Review & Board ReviewRouting Verification Records

39. Activation

40. Activations • Activation packets are routed within 1 day of distribution of approval memo • OHRS sends follow up reminders to activation agents at least once every 2 weeks • Advise activation agents of high priority circumstances

41. Activations • Absent justification and approval by the OHRS Senior Director/Deputy Director, studies must first be activated at the leadsite before being activated at any other participating site. • Before activating at a participating site, the lead site Pharmacy must sign off or you must check with the lead site Pharmacy to make sure that it is ok for other participating sites to be active (if it is high priority and needs to be activated ASAP). • DFCI Research Admin sign off is always needed (industry sponsored trials only) unless at BIDMC only. • If BWH is being added as a site (amendment) or if they are the only participating site, you must obtain DFCI Pharmacy, Nursing and Research Admin (industry sponsored trials only). • Pediatric vs. Adult sign off for pharmacy & nursing depends on which clinics are being utilized.

42. Activations • Problem Spots • Activation agents may require changes - “post approval/pre-activation” amendment process • In-services not complete • Waiting for drug • COE / doctor’s orders sheets • Funding issues • Amendment may be ready for activation at one site but not another – can only post one version to OncPro

43. Additional Considerations

44. Additional Considerations • Working on notification to study teams of new protocol assignment to HRC • Working on updating informed consent template • Please remember to use most current versions of forms available at website • If you have a complicated submission, please feel free to call OHRS for guidance • Let us know when changes are good and we are on the right track

45. OHRS Contacts • OHRS website: • www.dfci.harvard.edu/ohrs • OHRS front desk: • (617) 632-3029