1. CTMS Workspace Face to Face February 04, 2010 Houston, TX David Loose Essex Management - CBIIT National Cancer Institute NCI Clinical Trials Reporting Program Implementation 1

2. Agenda Origin and Rationale Value add / community services NCI Vision Status of NCI alignment CTRP Status Registration requirements / timeline Feedback / community interaction Subcommittee status / efforts Pilot sites / Early adopters Key Issues

3. Origin: Clinical Trials Working Group (2005) NCI Trial/Study Analysis How many new/ongoing Number of studies by type, center, etc. Trial/Study Performance Accruals (#patients enrolled) Trial/Study Effectiveness AEs Outcomes

4. Rationale for a Clinical Trials Reporting Program (CTRP) NCI has no electronic database for more than half of its clinical trials portfolio (> 20,000 patients accrued per year) R01s, R21s, P01s, SPOREs etc. Institutionally-supported using CCSG resources Currently available databases do not allow NCI and the broader cancer community to: Identify toxicity trends for public safety, Manage portfolio accountably by monitoring accrual, identifying gaps and duplicative studies Effectively prioritize clinical trials

5. Clinical Trials Reporting Program A comprehensive resource of NCI-supported clinical trial data to facilitate better planning and management across clinical trial venues Transparency on the status and scope of the broad cancer research enterprise based on NCI-supported organizations Inclusion of data from other sponsors (public and private sector) Enhanced ability to mine, compare and analyze data across trials Leveraging of NCI’s experience and expertise in the design, development, deployment and maintenance of clinical trials databases

6. FDA Amendment Act (FDAAA) of 2007 and NIH policy FDA Amendment Act (FDAAA) of 2007 Requires registration of all applicable trials (Phase II/III) with ClinicalTrials.gov Sets rules for determining “Responsible Party” for this activity Penalties for non-registration include large fines and withdrawal of NIH funding Substantive outcomes reporting requirements NIH policy: It is no longer permissible for NIH institutes to register trials on behalf of Responsible Parties (e.g., via any NCI system) NCI is not in control of these requirements

7. Value-Added of NCI’s CTRP Registration 2005: Voluntary ClinicalTrials.gov registration from NCI Registry Grantee  Registration  NCI Trials Registry (PDQ)  ClinicalTrials.gov 2007: FDAAA requires registration and outcomes by Responsible Party. NIH policy prohibits registration by any Federal System Grantee  NCI Trials Registry (PDQ)  X  ClinicalTrials.gov 2009: CTRP enhanced to abstract information for ClinicalTrials.gov registration and return file to Grantees for independent validation and submission Grantee  Registration  NCI Trials Registry (CTRP)  TSR XML  Grantee  Registration  ClinicalTrials.gov Registration Grantee NCI Trials Registry (PDQ) ClinicalTrials.gov TSR XML Registration Grantee NCI Trials Registry (CTRP) Registration Grantee NCI Trials Registry (PDQ) ClinicalTrials.gov 2005: Voluntary ClinicalTrials.gov registration from NCI Registry 2007: FDAAA requires registration and outcomes by Responsible Party. NIH policy prohibits registration by any Federal System 2009: CTRP enhanced to abstract information for ClinicalTrials.gov registration and return file to Grantees for independent validation and submission Grantee Registration

8. CTRP Services to the Cancer Community Performs the abstraction of data that may be suitable for Clinical Trials.gov reporting 40 FTE positions to be funded by NCI, currently at 11 FTEs CTRP/CTRO develops the lay language description of the protocol Provides a data file Data can be uploaded to ClinicalTrials.gov so that dual entry for required elements is unnecessary Data can be used for local data management Provide clinical trials management tools for Centers Generates “Summary 4” table Note: Full implementation requires Cooperative Group data and more Interoperable with commercial clinical trials systems; NCI will also work with Cancer Centers that have developed own in-house systems

9. CTRP Reporting Capabilities This single portal will meet the NCI’s and the cancer research community’s current and future reporting needs Feature – Availability of PDQ/CTRP Basic search capability for protocol information – PDQ and CTRP Enhanced search capability for NCI’s website (Cancer.gov) – PDQ and CTRP Complete and comprehensive listing of all NCI supported clinical trials – CTRP Accrual Data – CTRP Patient level demographic data (Similar to CDUS abbreviated) – CTRP Patent level outcome data (Similar to CDUS complete) FeaturePDQCTRP Basic search capability for protocol information Enhanced search capability for NCI's website (Cancer.gov) Complete and comprehensive listing of all NCI supported clinical trials Accrual data Patient level demographic data (similar to CDUS abbreviated) Patient level outcome data (similar to CDUS complete)

10. ClinicalTrials.gov Capabilities The information in ClinicalTrials.gov does not meet the NCI’s or the cancer research communities’ current and future needs Feature – Availability of PDQ/CTRP/CT.gov Basic search capability for protocol information – PDQ, CTRP, and CT.gov Enhanced search capability for NCI's website (Cancer.gov) – PDQ and CTRP Complete and comprehensive listing of all NCI supported clinical trials – CTRP only Accrual Data – CTRP only Patient level demographics (similar to CDUS abbreviated) – CTRP only Patient level outcomes (similar to CDUS complete) – CTRP only FeaturePDQCTRPCT.gov Basic search capability for protocol information Enhanced search capability for NCI's website (Cancer.gov) Complete and comprehensive listing of all NCI supported clinical trials Accrual data Patient level demographics (similar to CDUS abbreviated) Patient level outcomes (similar to CDUS complete)

11. CTRP Technology Capabilities The CTRP system utilizes a state-of-the-art design, developed around structured data that enables integration with Cancer Center systems to automate reporting requirements Feature – Availability of PDQ, CTRP, CT.gov Relational Database – PDQ, CTRP, and CT.gov Web user interface – PDQ, CTRP, and CT.gov Reporting capability - CT Industry Standard Information to allow sharing of data – CTRP only Electronic reporting standardization aligned with FDA requirements – CTRP only Open design enabling information exchange with all internal NCI systems – CTRP only Open design enabling information exchange with Cancer Center clinical trial systems – CTRP only FeaturePDQCTRPCT.gov Relational Database Web user interface Reporting capability Industry Standard Information to allow sharing of data Electronic reporting standardization aligned with FDA requirements Open design enabling information exchange with all internal NCI systems Open design enabling information exchange with Cancer Center clinical trial systems

12. CTRP and NCI Enterprise Services caGrid NCI Clinical Trials Reporting Program Firebird caBIG ® (caAERS, PSC, C3PR, C3D) PLT caTisse caEHR Business Registration Protocol Study Outcomes Clinical Research Qry Eligibility Adverse Event Hx and Physical Discharge Note Decision Support Referral and Authorization Capability Credentialing Specimen Treatment Plan Image Lab Pharmacy Scheduling CORE SDTM Data Query Correlation Organization Person Protocol Abstraction Disease Agent Master Problem List Allergy Infra/Utility Knowledge Management Contract Management Enterprise Vocabulary Validation Transition Audit Id Management Trust Management Authorization Authentication Policy 12 NCI Clinical Trials Reporting Program ca- AERS PSCC3PRC3D caBIG ® Clinical Trials Suite caGrid R Registration Ae Adverse Event Pt Protocol caTissuecaEHR “B USINESS ” “ C ORE ” PLTFirebird “C APABILITY ” S Specimen Sc Scheduling Tx Translation Au Audit Ra Referral and Authorization Hx Hx and Physical Va Validation Ev Enterprise Vocabulary O Organization P Person A Agent D Disease C Correlation Pa Protocol Abstraction Dx Discharge Note Cq Clinical Research Qry Tp Treatment Plan Ds Decision Support I Image L Lab Rx Pharmacy “Infra / U TILITY ” Cm Contract Management Mp Master Problem List Ay Allergy Sd SDTM E Eligibility Km Knowledge Management Cr Credentialing Oc Study Outcomes Qr Data Query Id Management Tr Trust Management Aa Authorization Authentication Py Policy

13. Long Term Vision – Single Database NCI-Designated Cancer Centers, Cooperative Group and other participating sites  NCI Staff enter clinical trial information  NCI Sponsor (CTEP and DCP) NCI Participating Site and IRB Management (RSS) NCI CTRP (Registration) Site Registers with Clinicaltrials.gov NIH/NLM ClinicalTrials.gov  Unidirectional update of non-NCI trials only from ClinicalTrials.gov to NCI Enterprise Services NCI CTRP (Registration)  Sites register investigator-initiated trials with CTRP, receive back XML files for investigator initiated and Grant funded trials  NCI-designated Cancer Centers, Cooperative Group and other Participating Sites Industry and Other Non-NCI Sponsors  industry sponsors register trials  NIH/NLM ClinicalTrials.gov NCI-designated Cancer Centers and other participating sites NCI Sponsor (CTEP and DCP) NCI Public Trials Portal (Cancer.gov) NIH/NLM Clinical Trials.gov NCI staff enter clinical trial information Site registers with Clinicaltrials.gov Unidirectional update of non-NCI trials only from ClinicalTrials. gov to NCI Enterprise Services Industry and other Non-NCI Sponsors Industry sponsors register trials NCI-designated Cancer Centers and other participating sites NCI-designated Cancer Centers and other participating sites NCI-designated Cancer Centers and other participating sites NCI-designated Cancer Centers and other participating sites NCI-designated Cancer Centers, Cooperative Group and other participating sites Industry and other Non-NCI Sponsors Industry and other Non-NCI Sponsors NCI Participating Site and IRB Management (RSS) NCI CTRP (Registration) NCI Enterprise Services Sites register investigator-initiated trials with CTRP, receive back XML files for investigator initiated and Grant funded trials

14. Current/Near Term Process (4Q2009) NCI-Designated Cancer Centers, Cooperative Group and other participating sites  CTEP/DCP enter clinical trial information  NCI Sponsor (CTEP and DCP)  Clinical trials and site status periodically loaded from CTRP/DCP and RSS to NCI Enterprise Services  NCI Enterprise Services Local IRB information for group trials sent by a sites to CTEP RSS  NCI Participating Site and IRB Management (RSS)  Enterprise Services Sites register investigator-initiated trials with CTRP, receive back XML files for investigator initiated  NCI CTRP (NCI Enterprise Services) NCI CTRP (Registration)  Sites register investigator-initiated trials with CTRP, receive back XML files for investigator initiated and Grant funded trials  NCI-designated Cancer Centers, Cooperative Group and other Participating Sites Industry and Other Non-NCI Sponsors  industry sponsors register trials  NIH/NLM ClinicalTrials.gov NCI-designated Cancer Centers and other participating sites NCI CTEP/DCP NCI OCE PDQ NIH/NLM Clinical Trials.gov CTEP/DCP staff enter Clinical trial information Site registers with Clinicaltrials.gov Unidirectional update from ClinicalTrials.gov to PDQ Industry and other Non-NCI Sponsors Industry sponsors register trials Local IRB Information for Group Trials sent by sites to CTEP RSS Clinical Trials and site status periodically loaded from CTEP/DCP and RSS to NCI Enterprise Services NCI-designated Cancer Centers and other participating sites NCI-designated Cancer Centers and other participating sites NCI-designated Cancer Centers and other participating sites NCI-designated Cancer Centers and other participating sites NCI-designated Cancer Centers, Cooperative Group and other participating sites Industry and other Non-NCI Sponsors Industry and other Non-NCI Sponsors NCI CTEP CTSU RSS NCI CTRP NCI Enterprise Services Sites register investigator-initiated trials with CTRP, receive back XML files for investigator initiated

15. NCI Clinical Trials Website

16. Timeline: CTRP Application 1.0 Protocol Abstraction – January 2009 2.0 Protocol Amendments – June 2009 3.0 Proprietary Trials – December 2009 Will also include vendor/center access to Protocol Service 3.1 Accruals – January 2010 – Pilot Phase Accruals based on “CDUS Abbreviated” data elements, patient by patient via website 3.2 Feature enhancements – Q2 2010 Batch accrual solution, partial saves, RSS integration, service/user enhancements

17. CTRP Metrics as of January 14, 2010 1824 Clinical Trials in CTRP 880 Registered by Cancer Centers in CTRP 410 Non-proprietary, 470 Proprietary Breakdown by pilot sites/early adopters/good citizens 944 loaded from CTEP and DCP Cancer Center registrations by month in 2009

18. CTRP Metrics as of January 14, 2010 30 Cancer Centers with at least one Clinical Trial Registered

19. CTRP Metrics as of January 14, 2010 30 Cancer Centers with at least one Clinical Trial Registered

20. NCI Cooperative Group / CCOP Trials Pre-CTRP – Trials Registration via NCI/CTEP Trial Registry CTRP – Trial registration via NCI Trial Registry (CTRP); No change NCI Non-Group / CCOP Trials (Investigational Drug Branch Trials (N01/U01)) Pre-CTRP – CDUS Abbreviated* CTRP – No Change Grant and SPORE Trials (Other NCI-funded trials (R01, R21, P01, SPORE etc.) and other Institutional Interventional Clinical Trials) Pre-CTRP - CDUS Complete** CTRP – No Change Grant and SPORE Trials ( Other NCI-funded trials (R01, R21, P01, SPORE etc.) and other Institutional Interventional Clinical Trials) Pre-CTRP Trial registration via NCI Trial Registry (PDQ; pre-2010) or CT.gov Annual reporting of list of trials and accrual for Summary 4 CTRP Trial registration via NCI Trial Registry (CTRP) Accrual Date Automated preparation of data for annual Summary 4 reporting *Patient level accrual **Patient level outcomes and toxicity Initial Registration and Reporting Requirements Pre-CTRPCTRP NCI Cooperative Group / CCOP Trials NCI Non-Group / CCOP Trials ( Investigational Drug Branch Trials (N01/U01)) Trial registration via NCI/CTEP Trial Registry CDUS Abbreviated* CDUS Complete** Trial registration via NCI Trial Registry (CTRP); No change No change Grant and SPORE Trials ( Other NCI-funded trials (R01, R21, P01, SPORE etc.) and other Institutional Interventional Clinical Trials) Trial registration via NCI Trial Registry (PDQ; pre- 2010) or CT.gov Annual reporting of list of trials and accrual for Summary 4 Trial registration via NCI Trial Registry (CTRP) Accrual data Automated preparation of data for annual Summary 4 reporting

21. Reporting Timelines Initially, NCI expects new trials initiated after production date of 1/1/2009 to be registered Trials that are new as of the date CTRP is open to a Center should be registered prior to first patient enrollment All active trials to be entered within six months of first trial registration Submission of amendments is requested prior to next patient enrolled January 2010, pilot of quarterly entry of accrual information Late 2010 - AEs, Outcomes, Observational, Ancillary, etc.

22. Pilot cancer centers: New Trials – January 2009 New and Existing trials, amendments – July 2009 through June 2010 Accruals Pilot – January 2010 through March 2010 Ongoing Registrations – June 2010 and ongoing “Early Adopter” Cancer Centers: New Trials, amendments – July 2009 through October 2009 New and existing trials, amendments – October 2009 through June 2010 Ongoing Registrations – June 2010 and ongoing All Remaining Cancer Centers: New Trials, amendments – October 2009 through January 2010 New and existing trials, amendments – January 2010 through June 2010 Ongoing Registrations – June 2010 and ongoing Non-Cancer Center Grantees: New trials, amendments – January 2010 through March 2010 New and existing trials, amendments – March 2010 through July 2010 Ongoing Registrations – July 2010 and ongoing All Grantees Accruals – March 2010 and ongoing Observational / Ancillary / Correlative? – July 2010 and ongoing New trials January 2009 October 2009 January 2010 July 2009 June 2010 Pilot Cancer Centers New and existing trials, amendments New trials, amendments New and existing trials, amendments All Remaining Cancer Centers New trials, amendments New and existing trials, amendments Non-Cancer Center Grantees New and existing trials, amendments Accruals Pilot All Grantees Accruals Observational / Ancillary / Correlative? March 2010 September 2010 Ongoing Registrations Ongoing Registrations Ongoing Registrations New trials, amendments Ongoing Registrations “Early Adopter” Cancer Centers Informatics Technology and Adoption Timeline

23. Partnering with the clinical trials community Developing implementation and adoption timelines Implementation Timeline – Technology – Cancer Community Registration – Ready – 2010 System Integration (caBIG ® Enterprise Services) – Ready - ? Accrual – Ready - ? Patient level demographics file loader format (similar to CDUS abbreviated) – Q2 2010 - ? Patient level outcomes (similar to CDUS complete) – Q4 2010 - ? Implementation TimelineTechnology Cancer Community RegistrationReady 2010 System Integration (caBIG ® Enterprise Services)Ready ? AccrualReady ? Patient level demographics file loader format (similar to CDUS abbreviated)Q2 2010 ? Patient level outcomes (similar to CDUS complete)Q4 2010?

24. Feedback venues National Cancer Advisory Board Determined need for CTRP High level monitoring of CTWG initiatives Clinical and Translational Research Advisory Committee (CTAC) Advisory Committee on deployment of CTWG initiatives; meets quarterly caBIG ® Clinical Trials Management Systems Steering Committee CTRP Subcommittee: conference calls weekly on deployment strategy, reporting capability Pilot Site calls Conference calls weekly on operational issues

25. Clinical Trials Reporting Program (CTRP) Subcommittee (* = SC members) Extramural *Bob Annechiarico, Duke University Cancer Center Rhoda Arzoomanian, University of Wisconsin Alyssa Dellacroce, Dana-Farber Cancer Institute Shannon Nelson, Dana-Farber Cancer Institute Rob DuWors, University of California Los Angeles *Sharon Elcombe, Mayo Clinic Cancer Center *Charlie Hurmiz, St. Jude Children's Research Hospital Tim Peters, M.S., Children's Oncology Group Bob Morrell, Wake Forest University *Sorena Nadaf, University of California San Francisco Mary Sumpmann, University of Minnesota *Dan Sargent, Ph.D., Mayo Clinic College of Medicine NCI Staff John Speakman, CBIIT *Linda Weiss, Ph.D., OCC Christo Andonyadis, D.Sc., CBIIT David Loose, CBIIT Joe Martucci, CCCT Gisele Sarosy, M.D., CCCT

26. Clinical Trials Reporting Program (CTRP) Subcommittee Remit: Provide feedback on the CTRP deployment effort and strategic guidance on issues/risks Dana Farber presented on pilot experience CCAF members of the subcommittee surveyed member sites on opportunities/challenges for CTRP deployment We plan to send out quarterly CTRP Update communications to Cancer Center Directors and Administrators Proposed extended remit: Need clinicians and administrators to provide feedback on the types of queries / reports that CTRP should be able to respond to / deliver Assist with communications to the research community

27. Clinical Trials Reporting Program Subcommittee Update Reviewed and provided feedback on the survey issued to the Cancer Center Administrators Forum (CCAF) Outcome: Many centers are not knowledgeable about CTRP Next Steps Review and provide feedback on Physician Data Query (PDQ) transition timelines and activities Plan for CTRP communications efforts to the remaining cancer centers and the grantee community

28. Volunteer Pilot / Early Adopter sites Pilot: Dana-Farber, Mayo, Northwestern, St. Jude, Wake Forest Early Adopters: Case Western, Columbia University, Fred Hutchinson, New York University, Duke, Johns Hopkins, Memorial Sloan-Kettering, University of Virginia, City of Hope, Fox Chase, Georgetown, MD Anderson, Penn, Roswell Park, Thomas Jefferson, University of California Davis, University of California Irvine, University of California San Diego, University of Nebraska, University of Southern California Early Adopter calls in January

29. Key Issues System – System integration PDQ Submission Proprietary Trials – solution in place CTRP alignment with ClinicalTrials.gov Communications

30. Proprietary Trials How will CTRP handle industry trials in which information in the protocol document may be proprietary? New approach (pilot started December 2009) Request NCT number (ClinicalTrials.gov identifier) and local implementation information CTRO obtains record from ClinicalTrials.gov for registration in CTRP Immediate spike in proprietary trial registration with release of CTRP 3.0 – Proprietary Trial workflow Submission of industry trials, and other trials not directly supported by NCI, is only expected for NCI-designated cancer centers

31. CTRP XML use Concerns have been raised on CTRP and CT.gov record alignment with respect to use of CTRP XML The process as-is today for ensuring alignment: The CTRO abstracts protocols following NCI established procedure CTRO provides a TSR for review, and an XML file for use in other systems CTRO welcomes feedback/corrections on errors in the Trial Summary Report, but cannot address changes if they conflict with NCI procedure Changes must originate in CTRP to maintain consistency. If changes are made to a record elsewhere, they will not be reflected in the CTRP database or XML

32. CTRP User Resources Trial registration website: https://trials.nci.nih.gov/registry/home.action https://trials.nci.nih.gov/registry/home.action Visit this website to register trials with the NCI’s CTRP and to search CTRP registered trials CTRP informational website: http://www.cancer.gov/clinicaltrials/ctrp http://www.cancer.gov/clinicaltrials/ctrp Resources include FAQs, Glossary, and a CTRP User’s Guide CTRP Forum : https://cabig- kc.nci.nih.gov/CTMS/forums/viewforum.php?f=31https://cabig- kc.nci.nih.gov/CTMS/forums/viewforum.php?f=31 Visit the forum to ask questions of the CTRP team and other CTRP users; please note – an account is required to post messages CTRP-USERS-L@list.nih.gov – CTRP Users ListservCTRP-USERS-L@list.nih.gov NCICTRP@mail.nih.gov – Program questionsNCICTRP@mail.nih.gov NCICTRO@mail.nih.gov – Clinical Trials Reporting OfficeNCICTRO@mail.nih.gov

33. Questions?