CCOP, MBCCOP Research Base Meeting

1. CCOP, MBCCOP & Research Base Meeting September 17-18, 2007 Joan K. Mauer, Chief Linda McClure, Clinical Trials Monitoring Specialist Clinical Trials Monitoring Branch Cancer Therapy Evaluation Program Division Of Cancer Treatment and Diagnosis NCI, NIH

2. INTRODUCTION CTEP/NCI sponsors approximately 135 active INDs at any given time Clinical trials are conducted through clinical Cooperative Groups and Cancer Centers Approximately 28,000 new patients are enrolled annually in treatment trials

3. Overview NCI�s Clinical Trials Cooperative Group Program (the �Groups�) is distinctive among NIH-supported clinical trials programs: A standing clinical trials infrastructure that is continuously available to test new therapeutic strategies Consists of researchers at institutions affiliated with the Groups who jointly develop and conduct trials in multi-institutional settings Flexible research agenda allows change of strategy in response to changing scientific opportunities and new discoveries

5. NCI Cooperative Group Program 2007: 10 Groups - 9 adult and 1 pediatric Multimodality: Cancer and Acute Leukemia Group B (CALGB) Eastern Cooperative Oncology Group (ECOG) North Central Cancer Treatment Group (NCCTG) Southwest Oncology Group (SWOG) NCI of Canada � Clinical Trials Group (NCIC-CTG)** Specialty: American College of Surgeons Oncology Group (ACOSOG) National Surgical Adjuvant Breast & Bowel Project (NSABP) Gynecologic Oncology Group (GOG) Radiation Therapy Oncology Group (RTOG) Children�s Oncology Group (COG) ** NCIC-CTG funding limited to participation in Intergroup trials

6. Cooperative Group QC and QA Program Groups have well established QC programs for monitoring data through statistical office 1982 on-site audit required for Cooperative Group Program with NCI oversight NCI standardized guidelines used to conduct audits Each Group institution audited at least once every 3 years

7. Data Monitoring Continuous process through-out the trial Off-site Includes all patients on the trial Auditing Independent review at one point in time On-site Based on PI & Institution, subset of patients on trial Data Monitoring vs Auditing

8. NCI Cooperative Group On-Site Audit Program Audit Program is Based on Institutions NOT specific trials Purpose of the on-site Audit Program: Document accuracy of data submitted to Groups with independent verification of study data with source documents Verify investigator compliance with protocol & regulatory requirements Serves as an educational tool opportunity for audit team to share with institution staff information on data quality, data management, & other aspects of QA

9. NCI Cooperative Group On-Site Audit Program 3 Components of Audit: IRB/Regulatory (IRB documentation; Content IC; AE & Safety Reports) Pharmacy (NCI DARFs; shipping/returns; shelf count, check pt records) Patient Case Review (Source Data Verification � Protocol Compliance) Informed Consent Eligibility Treatment Toxicity Data Timeliness - Quality

10. NCI Cooperative Group On-Site Audit Program Audit program based on institutional performance under a Principal Investigator for Cooperative Group at that site Auditing program is a independent review process with an educational component NCI standard guidelines for conduct of audits & requires all institutions be audited at least once every 36 months but all sites at risk for audit at any time (e.g., special audits) Clinical Trials Monitoring Branch (CTMB) at NCI/CTEP has direct oversight responsibility for the audit system Conducts Co-site visits on about 10% of all audits CTMB Auditing Guidelines publicly available at: http://ctep.info.nih.gov/monitoring/guidelines.html