1. WUSS 2009 CDISC for the Medical Device and Diagnostic Industry: An Update Carey Smoak Team Leader CDISC Device SDTM Sub-team

2. 2 Overview Device Team Importance of Devices Differences between Devices and Pharma Team Mission Possible Unique Device Identifier Current Status SAS and CDISC

3. Device Team >50 Team Members –Industry Experts –CDISC Representatives –FDA Representatives 3

4. Device Team Industry Experts –U.S. and Europe –Areas of Expertise Diagnostics Imaging Implantable Devices –Membership is open to anyone who wants to participate 4

5. 5 Device Team CDISC –SDS (Submission Data Standards) –CDASH (Clinical Data Acquisition Standards Harmonization) FDA –CDRH (Center for Devices and Radiological Health) –CBER (Center for Biologics Evaluation and Research)

6. 6 Importance of Devices Devices in and of themselves are important: –heart stents may save peoples’ lives –blood screening assays help to keep the blood supply safe

7. 7 Importance of Devices FDA –Last year (Jan-Nov, 2008), 697 Premarket Approvals (PMAs) were approved by CDRH –During the same time frame, 67 New Drug Applications (NDAs) were approved by CDER –This is not intended to imply that devices are more important than therapeutic products –Rather the point is simply that devices are important

8. 8 Importance of Devices Devices are also important when used in conjunction with therapeutic products –Contrast agents in imaging devices may be used to monitor therapeutic agents –Drug eluting heart stents may be used to treat cardiovascular disease –Diagnostic assays may be used to determine if a therapeutic product will work in a patient targeted therapies and companion diagnostics

9. 9 Differences between Devices and Pharma Paper by Greg Campbell (CDRH) –A medical device is anything that is not either a drug or a biologic product –Mechanism of action Medical devices are usually physical Pharmaceutical products are usually chemical or biological.

10. 10 Differences between Devices and Pharma –Type of Product Medical devices can be therapeutic, diagnostic or something else Pharmaceutical products are usually therapeutic –Research Medical devices are invented Drugs (new chemical entities) are generally discovered

11. 11 Differences between Devices and Pharma –Development Medical devices can be altered during clinical development Once on the market a newer, improved version may be in development Consequently, the life-cycle of a medical device may only be as short as a couple of years In contrast, drugs are usually on the market for many years

12. 12 Differences between Devices and Pharma –Approval Medical devices are approved through the Premarket Approval (PMA) application process A single confirmatory study is often sufficient for approval In contrast, drugs are approved through the New Drug Application (NDA) process Drug development is characterized by Phases I through IV clinical trials.

13. 13 Differences between Devices and Pharma –Companies There are more than 25,000 medical device companies registered with the FDA Medical device companies are usually small (the median size is less than 50 employees) In contrast, there are relatively few pharmaceutical companies Pharmaceutical companies tend to be large

14. 14 Differences between Devices and Pharma –Products There are tens of thousands of medical devices The number of drug numbers in the thousands

15. 15 Differences between Devices and Pharma In device studies, data is collected about: –Instruments –Assays –Specimens

16. 16 Differences between Devices and Pharma This data does not currently fit into any CDISC domain –“Houston, we have a problem.”

17. 17 Team Mission Possible Determine how device submission requirements fit within the context of SDTM Identify gaps and ways to address them Develop device domains as needed

18. Team Mission Possible February, 2009 INTRAchange –Device Team met with CDASH team and representatives from AdvaMed –Forged a strategy to: Review the 16 CDASH domains Create new device domains as needed 18

19. Team Mission Possible Review of 16 CDASH domains –CRF analysis sub-team –Collected more than 170 CRF from 40+ device companies 19

20. Team Mission Possible Create new device domains: –Device properties –Device disposition –Device accountability –Device malfunctions 20

21. 21 Team Mission Possible Device Properties (DP) –Properties and/or characteristics about a device –Findings observation class domain

22. 22 Team Mission Possible

23. Device Malfunctions –May or may not be related to an Adverse Event MedDRA Unique Device Identifier 23

24. 24 Unique Device Identifier On September 27, 2007 the FDA Amendments Act of 2007 was signed into law –This act includes language related to the establishment of a Unique Device Identification System

25. 25 Unique Device Identifier –This new system when implemented will require: the label of a device to bear a unique identifier the unique identifier to be able to identify the device through distribution and use the unique identifier to include the lot or serial number if specified by FDA

26. 26 Unique Device Identifier –This unique device identifier is currently a work in progress by the FDA –For more information, please go to www.fda.gov/cdrh/ocd/udi www.fda.gov/cdrh/ocd/udi

27. 27 New Domain Procedure An Initial Consensus Version (ICV) of the new SDTM and CDASH domains are achieved & other specific fields/terminology for the 16 CDASH Domains. Submit to CDISC Technical Leadership Committee and follow the Consensus Process. 27 Initial Consensus Version (ICV) TLC Review Harmonized Version (HV) External Focused Review Reviewed Version (RV) Public Review Released (Production) Version 1.0

28. 28 CDASH Component 16 Safety data domains developed Consolidated document posted for public review in May 2008 Received over 1800 comments from 46 companies, institutions and agencies. All 3 ICH regions were represented in the public comment process –US –Europe –Japan CDASH V1.0 published 2008 Streamlines data collection at investigative sites - addresses Critical Path Opportunity #45 Continuation of ACRO’s Initiative Started October 2006 Supported by a collaborative group of 17 organizations Core team of 16 members manages.. –11 working groups –Comprised of between 8-40 volunteers ~190 working group volunteers CDASH Project Snapshot

29. 29 CDASH Domains Common Identifier Variables Common Timing Variables Adverse Events (AE) Concomitant Medications (CM) Comments (CO) Drug Accountability (DA) Demographics (DM) Disposition (DS) Protocol Deviations (DV) ECG (EG) Exposure (EX) Inclusion Exclusion (IE) LAB Test Results (LB) Medical History (MH) Physical Exam (PE) Vital Signs (VS) Subject Characteristics (SC) Substance Use (SU) (N=16)

30. 30 CDASH Development Steps Review CDASH v 1.0 all domains Co- develop of SDTM domains –First time that this has been done –Device properties –Device disposition –Device accountability –Device malfunctions Focused on CRF Content, not CRF Layout

31. CDASH Development Steps Collected CRF samples – frequency analysis Evaluated commonalities/differences between CRF samples Documented data points included/excluded with justifications 31

32. CDASH Development Steps Agree on basic device CRF collection fields Assign Core Designation (Highly recommended, etc.) Map to draft SDTM domains 32

33. CDASH Development Steps Define required terminology – forward to Terminology team. Develop CRF question definitions and completion instructions for clinical sites and sponsors Incorporate new device domains into CDASH V 1.1 33

34. 34 CDASH- ODM Set-1 ODM & CRFs Set-2 ODM & CRFs Set-3 ODM & CRFs CDASH User Guide V 1.0 CDASH ODM CRFs CDASH DEVICE Properties Accountability Malfunction Initial Consensus Version (ICV) TLC Review Harmonized Version (HV) External Focused Review Reviewed Version (RV) Public Review Released (Production) Version 1.0 CDASH Program Plan 2009-2010 CDASH V 1.1 Correction /Additions Device domains CDASH- ODM ICVs Q409 CDASH-ODM CDASH V 1.1 CDASHUG 1.0 ICVs Q409 CDASH-ODM CDASH V 1.1 CDASHUG 1.0 CDISC CONSENSUS PROCESS Q2 10 Q4 09 Released Q2 10 CDASH-ODM CDASH V 1.1 CDASHUG 1.0 Released Q2 10 CDASH-ODM CDASH V 1.1 CDASHUG 1.0

35. SAS and CDISC Clinical Standards Toolkit which will: –Validate the CDISC SDTM standard (both WebSDM and Janus rules) –Produce the CRT-DDS (define.xml) documentation files –http://www.sas.com/news/preleases/062308/S ASforClinicalDI.html –Available with BASE/SAS 35

36. SAS and CDISC The Clinical Standards Toolkit is a set of macros which can be updated as standards change. This last point is of benefit to devices. –When a new SDTM standard becomes available for devices then the Clinical Standards Toolkit should work for devices. 36

37. SUMMARY Devices are important! Work is currently being done: –Review the 16 CDASH domains –Develop new domains New team members are welcome! 37

38. 38 Contacts Carey Smoak –Team Leader –Roche Molecular Systems, Inc. –E-mail: carey.smoak@roche.comcarey.smoak@roche.com