1. Annual Meeting 2011 Clinical Trial Development Clinical Trial Development: OEWG, RA’s Role, and Activating Trials on Deadline Martha Heckel Protocol Associate II, ACRIN Dept. of Protocol Development & Regulatory Compliance

2. Annual Meeting 2011 Clinical Trial Development Overview of Discussion Points 1.Introducing the OEWG Timeline 2.The RA in Early Trial Development 3.Trial Activation and Ramp-Up Phase

3. Annual Meeting 2011 Clinical Trial Development Introduction to OEWG 1. Introducing the OEWG Timeline: What is the OEWG? What is this about a timeline? How is it impacting ACRIN … the sites?

4. Annual Meeting 2011 Clinical Trial Development OEWG … What? What is the OEWG? OEWG = Operational Efficiency Working Group Established in 2008, the OEWG assessed how the cooperative groups function … and suggested changes.

5. Annual Meeting 2011 Clinical Trial Development OEWG … Why? Studies of timelines within the cooperative group structure show our processes can be improved … Dilts DM, Sandler AB. Activating and Opening Oncology Clinical Trials: Process & Timing Analysis. Available at: www.iom.edu/~/media/Files/Activity%20Files/Disease/NCPF/Dilts.pdf; accessed September 7, 2011. www.iom.edu/~/media/Files/Activity%20Files/Disease/NCPF/Dilts.pdf

6. Annual Meeting 2011 Clinical Trial Development OEWG Timeline The OEWG and CTEP have implemented target and absolute deadlines for concept development through actual trial activation. Trial activation is defined as one site ready to accrue participants.

7. Annual Meeting 2011 Clinical Trial Development OEWG Timelines: Target The OEWG guidelines include hard drop-dead dates depending on the phase of the treatment trial. Trial PhaseTarget DeadlinesAbsolute Deadlines Phase I210 Days540 Days Phase II210 Days540 Days Phase III300 Days720 Days

8. Annual Meeting 2011 Clinical Trial Development OEWG Timelines: Phases I and II Target Milestones

9. Annual Meeting 2011 Clinical Trial Development OEWG and ACRIN ACRIN will adhere to the same timelines, regardless of whether the trial is NCI funded or funded by another source (ACRIN Foundation, PA DoH, AHRQ). ACRIN will always have to work within OEWG structure for cooperative trials with other groups (e.g., ECOG, GOG, or RTOG).

10. Annual Meeting 2011 Clinical Trial Development OEWG Timelines: Impact Implications for ACRIN Procedures: More complete trial design prior to CTEP submission. Less complex trial designs. Forms and ancillary documents must be completed prior to activation. –Medidata RAVE and standardization

11. Annual Meeting 2011 Clinical Trial Development OEWG and ACRIN What changes have ACRIN and NCI introduced to meet the target deadlines? A.Shift in timing (earlier, earlier, earlier) B.Site membership C.Scanner qualifications D.Focus on activation/recruitment

12. Annual Meeting 2011 Clinical Trial Development OEWG and ACRIN A.Shift in timing (earlier, earlier, earlier) Delivery of materials to sites (protocol summary, PSA, etc) Streamlined development/ completion of forms Advanced oversight of contract negotiations

13. Annual Meeting 2011 Clinical Trial Development OEWG and ACRIN B.Site membership Centers for Quantitative Imaging Excellence, or CQIE Program (advanced imaging qualification program—NCI-designated Cancer Centers only) ECOG/ACRIN and ECOG membership

14. Annual Meeting 2011 Clinical Trial Development OEWG and ACRIN C.Scanner qualifications CQIE (CT, MR, PET) ACRIN will be working with sites to qualify imaging scanners using CQIE standards

15. Annual Meeting 2011 Clinical Trial Development OEWG and ACRIN D.Focus on activation/recruitment Earlier description of trial to sites; allow as much time as possible to review and consider joining the trial Consideration of the multidisciplinary team needed to perform the trial ECOG involvement will facilitate the connection between oncology and radiology as we join with treatment trials

16. Annual Meeting 2011 Clinical Trial Development OEWG and ACRIN D.Focus on activation/recruitment con’t Better understanding of sites’ processes, and how ACRIN can help … How many committees at your sites must review the protocol? On what timeline? How can ACRIN help?

17. Annual Meeting 2011 Clinical Trial Development OEWG and ACRIN D.Focus on activation/recruitment con’t Review of PSAs by multiple ACRIN departments and the trial PIs— plans for accrual Make sure sites aware of all open ACRIN trials

18. Annual Meeting 2011 Clinical Trial Development After Trial Activation TRIAL ACTIVATES!

19. Annual Meeting 2011 Clinical Trial Development 2. The RA in Early Trial Development: –Design: Consider Role of RA Committee Rep (Scientific and Procedural Input) Review of Protocol Contents –Implementation at sites: Anticipate Obstacles to Avoid Protocol Violations Ponder: What Tools Would Help Trial Process? During Early Trial Development

20. Annual Meeting 2011 Clinical Trial Development Trial assigned to a representative from the RA Committee RA Committee reps instrumental in forms development, which will have greater impact going forward … RA Committee Rep’s Role

21. Annual Meeting 2011 Clinical Trial Development Every RA has a role in trial development: Translation to local implementation Reasonable timelines for procedures Identifying pitfalls (obstacles to study compliance) And let us know at any time when you see areas for improvement Development and Implementation

22. Annual Meeting 2011 Clinical Trial Development Representative reviews the protocol/forms from data collection/operations perspective: How well are the procedures defined? Is the protocol consistent? What might be confusing to an RA (missing details)? During Trial Development

23. Annual Meeting 2011 Clinical Trial Development During Trial Development How Can ACRIN Help You? Help the Trial? During trial development, chime in with ideas to assist the trial: Eligibility flip charts Patient handouts Screening log

24. Annual Meeting 2011 Clinical Trial Development During Trial Development “I have ideas! Who’s my contact?” ACRIN’s Project Managers and Communications team leads the development of recruitment and other study-related materials. Call Nancy Fredericks to get started!

25. Annual Meeting 2011 Clinical Trial Development 3. Trial Activation and Ramp-Up Phase: Once the initial protocol is approved, ACRIN requests for local IRB submission no more than 30 days from receipt … maybe less depending on OEWG timeline! For amendments, ACRIN allows 60 days for protocol approval. Submitting to Local IRBs

26. Annual Meeting 2011 Clinical Trial Development During Trial Development Trial Development Is an Ongoing Process The conduct of the trial is important! We hope you will join our Site t-con calls and training. Contact us any time if you have specific feedback, e.g., see trends within a specific trial or across ACRIN trials.

27. Annual Meeting 2011 Clinical Trial Development “Why the push? Don’t we have 60 to 90 days for approval?” Yes, technically … But amendments are often in response to site feedback to eliminate accrual barriers or provide clarification. So, the sooner, the better! Submitting to Local IRBs

28. Annual Meeting 2011 Clinical Trial Development ACRIN trials would not be successful without our dedicated RAs. Thank you all for your commitment to ACRIN trials and the people who participate. We couldn’t do it without YOU! Thank You

29. Annual Meeting 2011 Clinical Trial Development Questions?