Cooperative group adoption of TBPT tools Barriers and Solutions Face to Face October 9, 2007

1. Cooperative group adoption of TBPT tools Barriers and Solutions Face to Face October 9, 2007 William G Richards, PhD Dave Billiter, PMP

2. Clinical Trials Cooperative Groups Program • 12 Cooperative groups • 1700 institutions • 22000 participants per year on treatment trials • Ideal source of cancer biospecimens • Large numbers of patients, representative of general population • Cohorts of patients uniformly treated and carefully followed • Prospective data collection, central data management • Central repositories, uniform handling, economies of scale • Logistical challenges to specimen banking • Participant institutions geographically dispersed • Shipping, tracking, quality assurance

3. Diverse sources of accrual to cooperative group trials Main Member Institutions Community Clinical Oncology Program Cooperative Group Trial Affiliate Institutions Institutions affiliated with Other Cooperative Groups Clinical Trials Support Unit

4. Barriers to using TBPT applications within Cooperative Group environment. • CAE • Difficult to implement centrally (isolated from institutional EMR) • Existing annotation and audit process • CRFs > DMC (error prone) • caTIES • No electronic access to Institutional Pathology reports • caTissue Core • Registration, consent, inventory, Q/C, and tracking data maintained in separate DBMS at separate sites • High-volume processing at repositories requires customized workflow management, minimal data entry, time efficiency • Group policies may limit annotation data that can be exposed • caTissue duplicates existing infrastructure that is “trusted” by IRBs • registration, consent monitoring, security, staff roles, PHI protection, blind correlative science, data monitoring, data sharing, etc.

5. Lung Cancer Tissue Bank (LCTB) • Use Case • 18 collecting sites, 1 Repository Lab, 1 Protocol • Collection events • Baseline blood >> LCTB • DNA > aliquots • Serum > aliquots • Frozen Tissue >> LCTB • Tumor > aliquot sets (variable #, +/- OCT) • Normal > aliquot sets (variable #, +/- OCT) • FFPE Tissue >> PCO • Tumor > block or 10 unstained slides • Follow-up blood >> LCTB • Serum > aliquots • Plasma > aliquots • Buffy coat

6. Data flow for CALGB Lung Cancer Tissue Bank Use Case Lung Cancer Tissue Bank Receive samples Data management center CALGB IS Inventory/QC Q/C Labtrak Collection site PCO Ship samples Receive samples Register Registration Inventory/QC Consent CRFs Protocol Data Leukemia Tissue Bank Inventory/QC

7. Lung Cancer Tissue Bank Inventory QC DBMS Lung Cancer Tissue Bank Inventory And Process Control DBMS Shipment Received Log case dates, patient ID, shipment ID Log sample sets by labtrak id Confirm contents Log subsamples Subprocessing Print Histology coding sheet for case Histology Nucleic acid extraction Log histology data, extraction Q/C Storage in freezer Track freezer space; Generate location codes Split aliquots among freezers; Print barcoded labels Log distribution Distribution

8. Specimen collection process - Labtrack data flow Approved Main Member or Affiliate LCTB Repository OSU PCO Ship Paraffin Block or Slides * Receive * Pre-op Blood Draw * R e g i s t e r Ship Blood * Receive * Extract DNA S t o r a g e Consent Serum Ship Tissue ± Serum * Q/C S t o r a g e Tissue* Tumor Lung Lymph node(s) S u r g e r y Receive * Receive * Ship Slides * H+E RNA F o l l o w u p S t o r a g e Post-op Blood Draw * Ship Blood * Receive * Q/C Plasma, buffy * Log in LabTrak Q/C

9. Group Banking Committee - Informatics Subcommittee • Cooperative groups charged with developing electronic reporting of Group biorepository inventory and utilization. • Standardize, use CDEs • Dynamic - update >= monthly • Accommodate variety of DBMS in use at Group Banks • Groups with > 1 biobank should coordinate reporting

10. Group Banking Committee (GBC)Reporting Mechanisms Dave Billiter, PMP Informatics Manager The Research Institute at Nationwide Children’s Hospital COG/GOG Tissue Bank

11. Gynecologic Oncology Group (GOG) Children’s Oncology Group (COG) American College of Surgeons Oncology Group (ACOSOG) Cancer and Leukemia Group B (CALGB) Eastern Cooperative Oncology Group (ECOG) North Central Cancer Treatment Group (NCCTG) Clinical Trials Group of the National Cancer Institute of Canada (NCIC CTG) National Surgical Adjuvant Breast and Bowel Project (NSABP) Radiation Therapy Oncology Group (RTOG) Southwest Oncology Group (SWOG) Cooperative Group Bank Participants

12. Group Banking Committee (GBC) • The purpose is to improve the operation of the clinical oncology cooperative group human specimen banks and to coordinate banking activities among groups conducting phase III and large phase II clinical trials. • To the extent possible, common collection and storage practices should be developed and implemented. • The GBC will act as a steering committee to develop policies with milestones for implementation.

13. Group Banking CommitteeFocus Areas • Coordination of Activities • Best practices for collection, storage and distribution of biospecimens • Common data structures for banking and data exchange • Principles and processes for utilization of banked specimens and data • Meeting the needs of emerging technologies

14. GBC Scope of Work • Extends to oversight of all aspects of the management and use of clinical oncology cooperative group human specimen banks and their resources. • Assumes coordination of processes by which the NCI or the individual cooperative groups choose which investigators are approved to access the specimens.

15. GBC Informatics Project Vision • Harmonization of Cooperative Group Banks • Standard Progress Reports • Functional data entry, report and query tool • Data exchange standard • Investigator query tool • Integration with other NCI programs

16. GBC Informatics Project Challenges • Requirements gathering • Communication • Group Buy-In • Resources • Technical Capabilities • Non-standardization • Prioritization

17. GBC Informatics Project Status • SDLC status (productype) • Technical contacts identified • Group Banks participation • Finalizing SOW

18. GBC Reporting Application Productype • http://www.c3big.org/GroupBankingCommittee/Login.aspx

19. CALGB proposal for Integrated GBC Reporting

20. Possible Grid-enabled solution for Integrated GBC Reporting Lung Cancer Tissue Bank CALGB Inventory (LCTB) Web Services Report Inventory [Insert / Update / Delete] caTissue Core Replication Interface CALGB Database Leukemia Registration Tissue Bank Report Inventory Consent (LTB) Publish Annotation Repository Inventory Management System (CALGBRIMS) Grid object Pathology Coordination Office (PCO) [Update Inventory] GBC Inventory Database

21. caTissue Migration Tool Data Pump Legacy Inventory DBMS Oracle or MySQL Database Staging caTissue DB Mapping Correct errors Resubmit records Error log Migration engine (caTissue API) Production caTissue Instance

22. Potential solution: Cross platform replication to caTissue Triggered updates Legacy Inventory DBMS Oracle or MySQL Database Staging caTissue DB Mapping Registration Correct errors Resubmit records Adjust source, mapping algorithms Specimen tracking Error log Migration engine (caTissue API) Annotation data Production caTissue Instance Q/C data

23. Possible obstacles • Straight forward adaptation of migration tool • Registration • Acquisition • Inventory management • Drop/replace versus additional development • Distribution • Subsampling • Consent status changes • on-study status changes • Relocation tracking

24. Advantages • Permit local UI customization independent of caTissue version upgrades • Publish only de-identified data to limit PHI exposure outside cooperative group firewall • GRID-enable cooperative group specimen inventory • leverage powerful query tool • fulfill GBC reporting commitments • allow cooperative groups to retain traditional data security function