1. National Cancer Institute Common Data Element (CDE) Activities and Plans September 8, 2015 Dianne M. Reeves Denise Warzel Center for Biomedical Informatics and Information Technology, NCI National Institutes of Health

2. Agenda Motivators and Objectives for NCI Initiatives Engagement with Community Groups Learning from our Experts Lessons Learned Basic Principles Can there be a downside to Sharing? Plans for the Next Five Years 2

3. Motivation for Change In 2015 there will be an estimated 1,658,370 new cancer cases and 589,430 cancer deaths - American Cancer Society 2015 Cancer remains the second most common cause of death in the U.S. - Centers for Disease Control and Prevention 2015 In 1998 the NCI published the first sustained decrease in deaths due to cancer since 1973, when records began to be collected. - New England Journal Medicine 2012; 366:2207-14 Today there are 14 million Americans alive with a history of cancer. It is estimated that by January 1, 2024, the population of cancer survivors will increase to almost 19 million: 9.3 million males and 9.6 million females - American Cancer Society 2015 3

4. Motivation for Change We must work together to adapt swiftly and effectively to achieve the goals of the new system—namely, to take advantage of recent advances in our understanding of cancer and to bring new knowledge into clinical trials conducted in the community. Our patients deserve nothing less. - Harold Varmus, Director, NCI, April 2014 4

5. NCI Milestones in Research and Discovery 1937National Cancer Act establishes NCI 1953NCI unveils full scale research programs –Cooperative group (extramural) program initiation 1967Drug cures for Hodgkins & childhood leukemia 1971National Cancer Act expands role of NCI 1974Adjuvant role for Breast Cancer established 1976Drug cures for Testicular carcinoma 1988Intensity modulated Radiation Therapy regimen 1989First human gene transfer trial 1995/96NCI Long Range Steering Committee established 1998Sustained cancer death incidence published 1999EDRN established 2005NCAB Clinical Trials Working Group Report 5

6. NCI Long Range Steering Committee (1995/96) 6 Now: Clinical trials produce eclectic data focused on the specific trial rather than a patient-centered record, most of which is paper-based and handled manually. There is no ‘systems approach’ to moving discoveries into routine care, and there is no national-scale infrastructure to support trials or basic research. Needed: All cancer clinical trials will have common terminology and reporting requirements, greatly increasing the speed and efficiency of conducting a trial and the accuracy of its results. Common data elements were constructed from the set of all data elements in an attempt to harmonize, standardize and simplify data collection requirements - Silva J, Wittes R, Proc AMIA Symp. 1999 : 950–954

7. NCI Milestones in CDE Activities 1953NCI Cooperative Groups created;9 Adult, 1 Pediatric 1974 Reorganization of intramural programs 1981Creation of PDQ 1982Monitoring/Reporting program I/Phase II trials 1995/96NCI CTEP Long Range Steering Committee –Need to standardize collecting and reporting across trials 2000NCI Metadata registry; load Coop group CDEs 2002Intramural program use of CDEs in trials 2003SPOREs, Imaging, other NCI CDEs registered 2005NCAB Clinical Trials Working Group Report 2005Launch of caBIG program accelerates CDE activity 2010 Institute of Medicine (IOM) Report 2014Relaunch of Cooperative Groups in NCTN Initiative Growing volume of valuable data over time 7

8. NCI CDEs and Registry Cancer Data Standards Registry and Repository (caDSR) Registry and Tooling a direct outgrowth of LRSC recommendations Established late 1990s to register and automate/share content Registration of human readable AND machine computable content Data elements (>50K) and collections (forms >3000; models) Nearly 1200 Standard/Candidate CDEs –CRF standards for Phase I/II/III clinical trials –Adverse Event reporting and integration elements –Patient Reported Outcomes/Health Related Quality of Life –BRIDG (ISO approved product from CDISC, NCI, FDA and HL7) The collection is not limited to standards Standards are found through the use of a registry attribute (flag) 8

9. Community Engagement – Content Experts Experts drive development of CDEs, never the reverse Reuse is desirable but not always obvious Some activities need large scale consensus-based workgroups for creation and vetting of CDEs NCI Network of Clinical Trials (NCTN) CRF standards NCI DCP Patient Reported Outcome/Health Related QoL Other activities/groups have required only the creation and maintenance expertise of CDE curators to register their work The Cancer Genome Atlas, TARGET, NCI SEER program, BRIDG, NAACCR, Imaging, CTD2 Groups that own content maintain revision rights and privileges over their content 9

10. Community Engagement – Content Curators Approximately 140 trained/skilled curators who create and maintain CDEs for initiatives Roles for –Context Administrator –Content Curator –Form Builder –Subject Matter Expert (SMEs) Training program for Roles with Preceptorship Monthly meetings with community members Involvement in software creation/requirements, testing Direct involvement in the review/creation Best Practices and SOPs Curators work with researchers to define CDEs 10

11. Lessons Learned The large volume of content has been difficult for users to navigate. They want simple and intuitive interactions with the registry and tools. A large registry of content reflects an evolution of best practices, business rules and software capability that newer users do not appreciate. The barrier to creation of CDEs must be low. The discoverability potential using CDEs is not obvious. Governance is critical in an environment of reuse and sharing. Decentralized curation supports scalability but puts more emphasis on QA, oversight and governance. Don’t invent new terms for things a community has described. Consensus-based harmonization requires resources and time. 11

12. Plans for the Next Five Years Support and harmonize new/ongoing research initiatives Streamline CDE creation and maintenance Increase automation to maximize knowledge extraction Continue collaboration with CFAST/CDISC to develop FDA- requested Therapeutic Area standards Work directly with applications (CDMS, REDCap) to facilitate the ease of creating collection and analysis formats Pursue opportunities to federate CDE collections Expand training program to include a ‘continuing education’ component Build and extend CDEs based on a common model such as BRIDG (CDISC/NCI/FDA/HL7 biomedical research model) Analyze registry content to identify Patterns and areas for improvement, harmonization and consolidation 12

13. Thank You! Dianne M. Reeves Program Manager, Biomedical Data Standards NCI CBIIT reevesd@mail.nih.gov Denise Warzel Program Manager, caDSR Software NCI CBIIT warzeld@mail.nih.gov CDE Browser: https://cdebrowser.nci.nih.gov/CDEBrowser/ CDE Wiki: https://wiki.nci.nih.gov/display/caDSR/caDSR+Hosted+Data+Standards %2C+Downloads%2C+and+Transformation+Utilities https://wiki.nci.nih.gov/display/caDSR/caDSR+Hosted+Data+Standards %2C+Downloads%2C+and+Transformation+Utilities 13