1. BRIDG SOP Harmonization Integrating caBIG™ SOPs with the BRIDG Implementation Model David Geismar Booz Allen Hamilton

2. Approach Activities for up front harmonization of role definitions for the BRIDG model and SOPs developed to support the caBIG™ program –Prioritization of SOPs for BRIDG Implementation Meet with SPR/BRIDG experts to determine an appropriate approach for creating SOP workflows using the BRIDG model –Create workflows directly in BRIDG version –Execute prototype or proof of concept –Assess and report on findings Continue mapping remaining SOPs (according to priority list)

3. Priority for BRIDG Integration (2nd year SOPs) The priority list of SOPs is based on relevance to the Structured Protocol initiative. Year 2 SOPs will be integrated initially thus avoiding any duplication of effort. –Study Lock and Close SOP –Study Reports (ISS & ISE formats) SOP –Statistical Analysis Plan SOP –Patient Registration (C3PR) SOPs –Clinical Data Management Plan SOP –Breaking the Statistical Blind SOP –Data Safety Monitoring Board Review (DSMB) SOP

4. Priority for BRIDG Integration (Year 1 SOPs) –SOP for Reconciliation of Serious Adverse Events (completed as a prototype) –SOP for Study Setup –SOP for Study Conduct –SOP for CRFs –SOP for CDE Curation –SOP for Application Standards Library Maintenance –SOP for Coding of Data –SOP for Electronic Loading of CDEs –SOP for Electronic Loading of Lab Data –SOP for Standard Programming –SOP for Establishing and Maintaining User Accounts –SOP for Retiring User Accounts –SOP for 21 CFR Part 11 Compliance

5. SOPs that may not be application for BRIDG Implementation at this time: –SOP for Security Compliance (HIPAA) –SOP for Patient Privacy (HIPAA) –SOP for SOPs (modeled by Bob Lanese) –SOP for Revisions and Deviations of SOPs –SOP for Release and Distribution of SOPs –Training (SOPs & personnel/qualification) –Revoking of Patient consent under HIPAA SOP

6. SOPSOP TitleSOPSOP Title AD001Develop and Maintain SOPsCR008Study Close SOP AD002Managing Deviations and Revisions to SOPsCR009Clinical Data Management Plan Guideline AD003Release and Distribution of SOPsCR010Data Safety Monitoring Board Review (DSMB) SOP AD004Information Security ComplianceCR011Breaking the Statistical Blind SOP AD005Protecting Patient Privacy (HIPAA)CR012Study Reports (ISS & ISE formats) SOP AD006Revoking of Patient consent under HIPAA SOPCR013Statistical Analysis Plan SOP AD007Training Process (on implementing SOPs training using CBT) SOPs CR014Patient Registration (C3PR) SOPs AD008Change Control (systems) SOPCV001Requirements for Complying with 21 CFR Part 11 CR001Study SetupCV002Computer Systems Validation SOP CR002Study ConductCV003Vendor Audit Guideline CR003Develop and Manage CRFsIT001Establishing and Maintaining User Accounts CR004CDE CurationIT002Retiring User Accounts CR005Application’s Standards Library MaintenanceIT003Electronic Loading of Laboratory Data CR006Coding of Clinical Research DataIT004Electronic Loading of CDEs CR007Reconciliation of SAE EventsIT005Standard Programming SOP Working Group Progress to Date Effective – Available for Use Approved by BP SIG – Not Available for Use Under review - Not Available for Use

7. SOPs currently harmonized in BRIDG Model SOPSOP Title AD006Revoking of Patient consent under HIPAA SOP AD007Training Process (on implementing SOPs training using CBT) SOPs CR007Reconciliation of Serious Adverse Events CR008Study Close CR010Data Safety Monitoring Board Review (DSMB) SOP CR011Breaking the Statistical Blind SOP CR012Study Reports (ISS & ISE formats) SOP CR013Statistical Analysis Plan SOP

8. Example Role Harmonization Matrix SOP Role/TitleResponsibility Description/ExamplesBRIDG Role/Title Application’s Standards Librarian  Works with the Study Design, the Study Coordinator, and when appropriate the caDSR Curator, to select CDEs that support protocol data collection requirements  Where required, works with the caDSR Curator to manage the process of loading and activating new CDEs within C3D  Act as liaisons between the clinical trials team and the caDRS curator to facilitate efficient and correct curation of CDE elements for C3D Does not exist caDSR Curator  Works with the C3D Study Coordinator and the C3D Application’s Standards Librarian as well as the CDE Requestor (for all other C3DS applications) to develop, review and construct for loading new CDEs required to support clinical trial research. Does not exist Loader Technician (for laboratory data)  Inspects external file  Conducts problem analysis and resolution Laboratory Technologist Principal/Primary Investigator  Responsible for following the blind and unblinding requirements as defined by the protocol.  Performs all screening investigations and compares the patient characteristics with the inclusion and exclusion criteria of the protocol.  Obtain authorization from human subjects that supply their data to the caBIG TM environment before disclosing it in any manner not previously described in the consent form. Principal Investigator Quality Assurance / QA Auditor  Audits all clinical research trial activities (e.g., monitoring activities, source document verification, AE reconciliation, coding activities, audits data captured on the CRF, audits and verifies training records)  Reviews patient eligibility and registration  Perform audit of the clinical trial research data.  Work with clinical data management, Study Coordinator, and/or Statistician to resolve any outstanding data issues prior to close or lock of the clinical research study. Auditor Research Nurse  Completes patient’s eligibility checklist. Research Nurse

9. National Cancer Institute Procedure Description SUBJECT: Breaking the Statistical Blind under the caBIG™ Program SOPPD No.: CR-011 StepAction 1DSMB, IRB or Subject’s Physician requests unblinded clinical research data when knowledge of the treatment assignment is deemed essential for the subject’s care A.DSMB requests clinical trial research data for review for safety issues. B.If applicable, DSMB or IRB will request from the statistician ‘unblinding’ of the patient population. 2Statistician/Pharmacist responds to unblinding requests A.After receiving a request from the DSMB or the IRB for the data to be unblinded, the Statistician or Pharmacist unblinds according to the protocol. B.Sends unblinded data to the DSMB or the IRB for their review. 3Clinical Study Team follows the blind and unblinding requirements A.If appropriate, the Clinical Study Team will remain blinded according to the clinical processes or protocol. B.Occurs with the support of the Statistician or the Principal Investigator.

10. SOP PD is translated into a workflow diagram

11. Workflow Guidelines/Rules Used Dynamic View to capture business process and stored workflows under Dynamic View – Staging Area-Business Process Decomposition - caBIG TM best practices SOP SIG subfolder

12. Workflow Guidelines/Rules (cont.) Used Logical View to capture roles used by the SOPs and stored them under Logical View – Logical Model – Staging Area - caBIG TM best practices SOP SIG subfolder

13. Workflow Guidelines/Rules (cont) SOP PD Workflows were created under one ‘Package’ A ‘Diagram’ to display the workflow was created using ‘Activity Behavioral Diagram’ ‘Activity’ boxes were used to describe specific procedures, these boxes were connected using ‘Control Flow’ within and across swim lanes ‘Decision’ boxes were also used and connected to ‘Activity’ boxes through ‘Control Flow’ ‘Notes’ were attached to ‘Control Flow’ arrows crossing swim lanes to show transferring of information

14. Workflow Guidelines/Rules (cont) Swim lanes were created using specific ‘Roles’ that correspond to caBIG TM best practices package classifiers Roles were created as a “generalization” of existing PersonRole public classes Documents were also created as Objects within the Logical model

15. EA Workflow Demo