Chiari Surgical Chiari Surgical Outcomes TrialOutcomes Trial

PI: Bermans J. Iskandar and PI: Bermans J. Iskandar and Timothy George with collaboration Timothy George with collaboration

from John Kestlefrom John Kestle ASAP-funded pilot studyASAP-funded pilot study

Initially suggested by Drs. Mihorat and BatzdorfInitially suggested by Drs. Mihorat and Batzdorf

Original plan led by Marcy SpeerOriginal plan led by Marcy Speer

Study supported by the American Society of Pediatric Study supported by the American Society of Pediatric Neurosurgeons (ASPN)Neurosurgeons (ASPN)

The University of Wisconsin (UW) Office of Clinical The University of Wisconsin (UW) Office of Clinical Trials is providing scientific, clinical and financial Trials is providing scientific, clinical and financial support in a collaborative effort to bring this trial to a support in a collaborative effort to bring this trial to a successful completionsuccessful completion

Title: Title: Outcomes in Patients Outcomes in Patients Undergoing Surgical Undergoing Surgical

Intervention for Chiari Type 1 Intervention for Chiari Type 1 Malformation with Malformation with

Syringomyelia Syringomyelia

Reasons for Study:Reasons for Study:

ASAP member survey regarding ASAP member survey regarding research needsresearch needs

ASPN member survey regarding ASPN member survey regarding methodologymethodology

Study GoalsStudy Goals

Direct goal:Direct goal: To collect pilot data to To collect pilot data to evaluate surgical approaches and evaluate surgical approaches and outcomes in surgery for patients outcomes in surgery for patients with Chiari I malformation with with Chiari I malformation with SyringomyeliaSyringomyelia

Indirect long-term goals: Indirect long-term goals: To generate preliminary data for a To generate preliminary data for a large federally-funded studylarge federally-funded studyTo initiate an organized To initiate an organized process/database by which Chiari and process/database by which Chiari and Syringomyelia can be studied in an Syringomyelia can be studied in an objective and consistent mannerobjective and consistent manner

Study MethodsStudy Methods

Prospective, multicenter trialProspective, multicenter trial

Surgeons follow their own routine in Surgeons follow their own routine in diagnosis, decision, and treatmentdiagnosis, decision, and treatment

Primary endpoint Primary endpoint Syrinx size postopSyrinx size postop

Secondary endpoints Secondary endpoints Symptom resolutionSymptom resolutionCine MRI and other radiographic Cine MRI and other radiographic outcomesoutcomes

Method Rigor and Method Rigor and Minimizing BiasMinimizing Bias

Independent reviewersIndependent reviewers: Committee of 3 : Committee of 3 (2 surgeons, one neuroradiologist) (2 surgeons, one neuroradiologist) evaluate all scans blindlyevaluate all scans blindly

Participating Centers: Participating Centers: Neither ASAP Neither ASAP Board members nor managing centers Board members nor managing centers (Wisconsin, Texas, Utah) were allowed to (Wisconsin, Texas, Utah) were allowed to participate in patient recruitmentparticipate in patient recruitment

Data gathering and study coordination: Data gathering and study coordination: All managed by a professional office with All managed by a professional office with experience in clinical trials - The UW experience in clinical trials - The UW Office of Clinical Trials (OCT)Office of Clinical Trials (OCT)

UW Office of Clinical UW Office of Clinical TrialsTrials(OCT)(OCT)

Provide professional clinical trial Provide professional clinical trial research experience and support research experience and support to any investigator who requires to any investigator who requires additional expertise to bring a additional expertise to bring a trial from a collaborative trial from a collaborative initiation to a successful initiation to a successful completioncompletion

OCT OCT Services Services ProvidedProvided

FinanceFinance

AdministrationAdministration

Regulatory complianceRegulatory compliance

Clinical study coordinationClinical study coordination

Typical Trial Typical Trial Process: Step IProcess: Step I

Trials originate from investigators or from Trials originate from investigators or from industry sponsors industry sponsors

A Confidential Disclosure Agreement (CDA) A Confidential Disclosure Agreement (CDA) may be initiated may be initiated

A Clinical Trials Agreement (CTA) is executed A Clinical Trials Agreement (CTA) is executed and routed through our university system to and routed through our university system to obtain institutional approvalsobtain institutional approvals

A feasibility review is conducted in A feasibility review is conducted in collaboration with the PI collaboration with the PI

Protocol is sent to Finance, Regulatory and to Protocol is sent to Finance, Regulatory and to the Clinical Coordinatorthe Clinical Coordinator

Typical Trial Process: Typical Trial Process: Step 2Step 2

Budget is negotiated, pricing is confirmed Budget is negotiated, pricing is confirmed and a preliminary budget is preparedand a preliminary budget is prepared

The Oncore database becomes activated The Oncore database becomes activated Protocol and Subject Life Cycle Protocol and Subject Life Cycle

ManagementManagement Subject Safety ManagementSubject Safety Management Protocol and Subject Calendar Protocol and Subject Calendar

ManagementManagement Electronic Data Capture & Data Electronic Data Capture & Data

ManagementManagement Study Information PortalStudy Information Portal Custom Reporting TechnologyCustom Reporting Technology

Typical Trial Process: Typical Trial Process: Step 3Step 3Oncore Database (cont’d)Oncore Database (cont’d) Electronic Data Capture & Data Electronic Data Capture & Data

ManagementManagement Study Information PortalStudy Information Portal Custom Reporting TechnologyCustom Reporting Technology

Oncore goal for the Chiari SurgicalOncore goal for the Chiari Surgical

Outcomes Study: Outcomes Study: To provide for a seamless transition to a larger trialTo provide for a seamless transition to a larger trial

Typical Trial Process: Step Typical Trial Process: Step 44 PI signs Office of Clinical Trials PI signs Office of Clinical Trials

agreement and it is executedagreement and it is executed

Clinical coordinator prepares the source Clinical coordinator prepares the source documents and data collection forms for documents and data collection forms for entry into the Oncore databaseentry into the Oncore database

Budget is finalizedBudget is finalized

Protocol IRB preparation is initiated and Protocol IRB preparation is initiated and submitted for approvalssubmitted for approvals

Typical Trial Process: Step Typical Trial Process: Step 55

IRB study approval is obtained and a recruitment IRB study approval is obtained and a recruitment plan is createdplan is created

A final meeting is scheduled with the PI to A final meeting is scheduled with the PI to confirm accrual, recruitment and accountabilityconfirm accrual, recruitment and accountability

Chiari Surgical Outcomes Chiari Surgical Outcomes TrialTrialStudy Objective: Study Objective: Collect pilot Collect pilot

data to evaluate surgical data to evaluate surgical approaches and outcomes in approaches and outcomes in surgery for patients with Chiari surgery for patients with Chiari I malformation with I malformation with SyringomyeliaSyringomyelia

Current Chiari Trial StatusCurrent Chiari Trial StatusSetup and IRBSetup and IRB

UW School of Medicine and Public Health UW School of Medicine and Public Health received received IRB approval IRB approval to be the data to be the data collection site for this study on 5/4/2009.collection site for this study on 5/4/2009.

Our site has IRB approval to collect data Our site has IRB approval to collect data from up to 12 clinical sites, from up to 12 clinical sites, 120 total 120 total subjectssubjects, no more than 10 subjects per , no more than 10 subjects per clinical site.clinical site.

Oncore research Oncore research database is completedatabase is complete and we are able to enter the data as we and we are able to enter the data as we receive it. We ran a test subject through receive it. We ran a test subject through the data collection process March 2010. the data collection process March 2010. This went smoothly with no glitches.This went smoothly with no glitches.

Current Study StatusCurrent Study StatusEnrollment to-dateEnrollment to-date

We currently have We currently have three active three active clinical sites clinical sites who have signed who have signed Clinical Trials Agreements with our Clinical Trials Agreements with our institution and their own IRB institution and their own IRB approvals are in place. approvals are in place.

Six clinical sites are in the clinical Six clinical sites are in the clinical trials agreement negotiation trials agreement negotiation process. process.

Four enrolled subjects Four enrolled subjects at this time. at this time.

Current Study StatusCurrent Study StatusProgress and ComplicationsProgress and Complications

No subject has withdrawn. No subject has withdrawn.

No subject has completed No subject has completed participation. participation.

No adverse events or protocol No adverse events or protocol violations reported.violations reported.

No changes in research plan, No changes in research plan, method or investigators. method or investigators.

Future Future ExpectationsExpectations

We are anticipating a two-year timeline to We are anticipating a two-year timeline to collect data on 100-120 subjectscollect data on 100-120 subjects

We anticipate collecting enough information We anticipate collecting enough information to achieve the following goals:to achieve the following goals:

Publish a feasibility study that would Publish a feasibility study that would facilitate obtaining NIH funding for a facilitate obtaining NIH funding for a large studylarge studyProvide preliminary but publishable data Provide preliminary but publishable data on differences in outcome between the 3 on differences in outcome between the 3 procedures to decompress a Chiari Iprocedures to decompress a Chiari I