1. Rare Diseases Clinical Research Network Data Management and Coordinating Center (RDCRN DMCC) Jeffrey Krischer, PhD LDN Investigator Meeting at WORLDSymposium 2016 March 4, 2016 The Rare Diseases Clinical Research Network (RDCRN) is coordinated by the Office of Rare Diseases Research (ORDR), NCATS. Funding and programmatic support is provided by ORDR in collaboration with participating NIH Institutes.

2. Goals of the RDCRN Facilitate clinical research by: – Creation of Consortia focused on related diseases – Cost-sharing research infrastructures – Establishing uniform protocols for data collection – Making meaningful large-scale studies possible Longitudinal cohorts, pilot projects, and randomized trials – Promulgating data standards Directly engage patients and their advocates Train new investigators in rare diseases research 2

3. History of the RDCRN Established by the Office of Rare Diseases Research Currently in the 3 rd 5-year cycle - 1st cycle (2003-2009): 10 Consortia - 2nd cycle (2009-2014): 19 Consortia - 3rd cycle (2014-2019): 22 Consortia Currently involves 267 institutions world-wide Collectively studying >200 diseases 41,519 patients enrolled in studies (during all 3 grant cycles) 3

4. Collaborative Clinical Research Public Resources and Education Centralized Data Coordination and Technology Development Training DHHS-NIH ORDR, NCATS, NINDS, NIAMS, NICHD, NHLBI, NIDDK, NIDCR, NIAID, NCI, NIMH, ODS The Data Management and Coordinating Center Coalition of Patient Advocacy Groups (CPAG) 4

5. RDCRN Data Management and Coordinating Center (DMCC) Supports RDCRN by providing technologies, tools, and support of study design and data analysis On-line protocol management system – Patient enrollment/randomization – Data entry and collection with data standards – Adverse event reporting Protocol training for research staff Members’ website: documentation, databases Hosts RDCRN public website (>2 million hits/year) Oversees the RDCRN Contact Registry 5

6. 267 clinical centers 144 patient advocacy groups 3,261 consortium members 21,259 study participants currently enrolled RDCRN Members Overview Data as of February 21, 2016 6

7. LDN Accrual by Protocol 7

8. Data Compliance Summary Data as of February 14, 2016 The DMCC provides data compliance reports for protocols that use the DMCC’s form system and for protocols that use the DMCC’s instance of REDCap. These reports indicate the status of data collection at each visit time point by form. LDN 6720 Example: The DMCC provides data compliance reports for protocols that use the DMCC’s form system and for protocols that use the DMCC’s instance of REDCap. These reports indicate the status of data collection at each visit time point by form. LDN 6720 Example: 8

9. RDCRN Contact Registry Data as of February 21, 2016 Goals: To inform registrants about RDCRN studies available; To disseminate information about RDCRN activities Overall (All consortia): 17,544 total registrations 17,544 total registrations 109 countries 109 countries 167 diseases represented 167 diseases represented LDN Contact Registry: 52 total registrations 52 total registrations 9 countries 9 countries 23 diseases represented 23 diseases represented 9

10. RDCRN Contact Registry Consortium Adaptations Consortia have adapted and enhanced the Contact Registry (CR) to fit their needs: Several consortia have conducted protocols through the CR. RTT - Auto-enrollment of longitudinal study participants in the CR VCRC - Auto-enrollment of Vasculitis Patient-Powered Research Network (V-PPRN) participants in the CR MCC - Collaborated with the PCD Foundation to develop a patient questionnaire; planning to expand the CR to serve as a broader patient registry for collection of patient-reported and clinical data CReATe - Enrollment of unaffected family members 10

11. Streamlined consent process Auto-enrollment into Contact Registry from protocols Enrollment of unaffected family members Email and logo customization for consortia and PAGs One account to cover multiple family members – Ex: one parent login for multiple affected children <18 Capability to select diseases across consortia Echoing information back to registrants Mobile friendly Support multiple languages RDCRN Contact Registry Enhancements 11

12. Contact Registry Enhancements Working Examples: Future Member Homepage (Left), Future Participant Summary (Right) 12

13. RDCRN Tools: RDCRN Data Explorer Purpose: To empower investigators and staff to explore, analyze, and share study data in a convenient and accessible environment. Platform contains study data and a suite of built-in tools to support interaction with the data. LDN data will be available in RDCRN Data Explorer starting in Spring. 13

14. Participants and parents can complete forms at home or online in clinic. Login information is the Participant ID and Local ID. If interested, this could be implemented in LDN protocols in the future. RDCRN Tools: Patient Portal 14

15. IRB of Record Coordinating Center The DMCC can interact directly with IRB of Record on consortium’s behalf to: Submit initial approvals, amendments, continuing reviews, and reportable events Respond to IRB queries Distribute IRB approved protocols, ICFs, etc. to sites 15

16. Consortia with IRB of Record: RLD, PIDTC, CEGIR, CReATe, UCDC, MCC, VCRC, NAMDC, DSC Additional Consortia Implementing IRB of Record: RKSC, NEPTUNE, STAIR, PC IRB of Record Coordinating Center 16

17. Certificate Training Program The Rare Diseases Clinical Research Training Program is recruiting for the 2016-2017 academic year One year course consists of both in-person and remote sessions Requires a 10% commitment from the program chair or department chair for focused research time Certificate awarded to participants completing at least 75% of the course content at or above acceptable levels Applications due on or before April 15, 2016 – Decisions will be made by June 1, 2016 For more information, please contact Dr. Debra Regier (dregier@childrensnational.org)dregier@childrensnational.org 17

18. The 4 th Conference on Clinical Research for Rare Diseases is scheduled for November 3, 2016 in Washington D.C. Educate new investigators in research techniques specific to rare diseases Full day program with poster session All Consortium PIs should plan to attend The RDCRN certificate program trainees from the past year and current year will be invited to attend – In addition, each consortium should sponsor 1 additional trainee to attend the CCRRD Supported by R13 conference grant; PAGs Clinical Research for Rare Diseases (CCRRD) 18

19. Thank you 19