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

4. U.S. Clinical Trials Treatment Sites(# of Sites by State that Currently have Patients Enrolled on Open Trials) United States (AK & HI Inset ) by Sites Total Sites = 1,878 2004 Data 1Dot = 5 sites

5. NCI Cooperative Group Program2007: 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 Both include expert Medical Review within the NCI Cooperative Group System with On-going Education for all Group Members

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