Surgical Outcomes in Patients with Chiari Type 1 Malformation and Syringomyelia

1. Chiari Surgical Outcomes TrialPI: Bermans J. Iskandar and Timothy George with collaboration from John Kestle • ASAP-funded pilot study • Initially suggested by Drs. Mihorat and Batzdorf • Original plan led by Marcy Speer • Study supported by the American Society of Pediatric Neurosurgeons (ASPN) • The University of Wisconsin (UW) Office of Clinical Trials is providing scientific, clinical and financial support in a collaborative effort to bring this trial to a successful completion

2. Title: Outcomes in Patients Undergoing Surgical Intervention for Chiari Type 1 Malformation with Syringomyelia Reasons for Study: • ASAP member survey regarding research needs • ASPN member survey regarding methodology

3. Study Goals • Direct goal: To collect pilot data to evaluate surgical approaches and outcomes in surgery for patients with Chiari I malformation with Syringomyelia • Indirect long-term goals: • To generate preliminary data for a large federally-funded study • To initiate an organized process/database by which Chiari and Syringomyelia can be studied in an objective and consistent manner

4. Study Methods • Prospective, multicenter trial • Surgeons follow their own routine in diagnosis, decision, and treatment • Primary endpoint • Syrinx size postop • Secondary endpoints • Symptom resolution • Cine MRI and other radiographic outcomes

5. Method Rigor and Minimizing Bias • Independent reviewers: Committee of 3 (2 surgeons, one neuroradiologist) evaluate all scans blindly • Participating Centers: Neither ASAP Board members nor managing centers (Wisconsin, Texas, Utah) were allowed to participate in patient recruitment • Data gathering and study coordination: All managed by a professional office with experience in clinical trials - The UW Office of Clinical Trials (OCT)

6. UW Office of Clinical Trials(OCT) Provide professional clinical trial research experience and support to any investigator who requires additional expertise to bring a trial from a collaborative initiation to a successful completion

7. OCT Services Provided • Finance • Administration • Regulatory compliance • Clinical study coordination

8. Typical Trial Process: Step I • Trials originate from investigators or from industry sponsors • A Confidential Disclosure Agreement (CDA) may be initiated • A Clinical Trials Agreement (CTA) is executed and routed through our university system to obtain institutional approvals • A feasibility review is conducted in collaboration with the PI • Protocol is sent to Finance, Regulatory and to the Clinical Coordinator

9. Typical Trial Process: Step 2 • Budget is negotiated, pricing is confirmed and a preliminary budget is prepared • The Oncore database becomes activated • Protocol and Subject Life Cycle Management • Subject Safety Management • Protocol and Subject Calendar Management • Electronic Data Capture & Data Management • Study Information Portal • Custom Reporting Technology

10. Typical Trial Process: Step 3 Oncore Database (cont’d) • Electronic Data Capture & Data Management • Study Information Portal • Custom Reporting Technology Oncore goal for the Chiari Surgical Outcomes Study: • To provide for a seamless transition to a larger trial

11. Typical Trial Process: Step 4 • PI signs Office of Clinical Trials agreement and it is executed • Clinical coordinator prepares the source documents and data collection forms for entry into the Oncore database • Budget is finalized • Protocol IRB preparation is initiated and submitted for approvals

12. Typical Trial Process: Step 5 • IRB study approval is obtained and a recruitment plan is created • A final meeting is scheduled with the PI to confirm accrual, recruitment and accountability

13. Chiari Surgical Outcomes Trial • Study Objective: Collect pilot data to evaluate surgical approaches and outcomes in surgery for patients with Chiari I malformation with Syringomyelia

14. Current Chiari Trial StatusSetup and IRB • UW School of Medicine and Public Health received IRB approval to be the data collection site for this study on 5/4/2009. • Our site has IRB approval to collect data from up to 12 clinical sites, 120 total subjects, no more than 10 subjects per clinical site. • Oncore research database is complete and we are able to enter the data as we receive it. We ran a test subject through the data collection process March 2010. This went smoothly with no glitches.

15. Current Study StatusEnrollment to-date • We currently have three active clinical sites who have signed Clinical Trials Agreements with our institution and their own IRB approvals are in place. • Six clinical sites are in the clinical trials agreement negotiation process. • Four enrolled subjects at this time.

16. Current Study StatusProgress and Complications • No subject has withdrawn. • No subject has completed participation. • No adverse events or protocol violations reported. • No changes in research plan, method or investigators.

17. Future Expectations • We are anticipating a two-year timeline to collect data on 100-120 subjects • We anticipate collecting enough information to achieve the following goals: • Publish a feasibility study that would facilitate obtaining NIH funding for a large study • Provide preliminary but publishable data on differences in outcome between the 3 procedures to decompress a Chiari I