WUSS 2009

CDISC for the Medical Device and Diagnostic Industry: An Update

Carey SmoakTeam Leader

CDISC Device SDTM Sub-team

2

Overview• Device Team

• Importance of Devices

• Differences between Devices and Pharma

• Team Mission Possible

• Unique Device Identifier

• Current Status

• SAS and CDISC

Device Team• >50 Team Members

– Industry Experts– CDISC Representatives– FDA Representatives

3

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

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

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

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

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

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

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

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

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

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

Differences between Devices and Pharma

– Products

• There are tens of thousands of medical devices

• The number of drug numbers in the thousands

15

Differences between Devices and Pharma

• In device studies, data is collected about:

– Instruments

– Assays

– Specimens

16

Differences between Devices and Pharma

• This data does not currently fit into any CDISC domain

– “Houston, we have a problem.”

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

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

Team Mission Possible• Review of 16 CDASH domains

– CRF analysis sub-team– Collected more than 170 CRF from 40+

device companies

19

Team Mission Possible• Create new device domains:

– Device properties– Device disposition– Device accountability– Device malfunctions

20

21

Team Mission Possible

• Device Properties (DP)– Properties and/or characteristics about a

device– Findings observation class domain

22

Team Mission Possible

Domain DPTESTCD DPTEST DPORRES DP DPMODEL Model

Number ABCDEF

DP DPSNUM Serial Number

123456

DP DPSVER Software Version

1.2.3

Team Mission Possible• Device Malfunctions

– May or may not be related to an Adverse Event

• MedDRA• Unique Device Identifier

23

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

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

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

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

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

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

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

CDASH Development Steps• Collected CRF samples – frequency

analysis

• Evaluated commonalities/differences between CRF samples

• Documented data points included/excluded with justifications

31

CDASH Development Steps• Agree on basic device CRF collection

fields 

• Assign Core Designation (Highly recommended, etc.)

• Map to draft SDTM domains

32

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

CDASH Program Plan 2009-2010

ICVs Q409CDASH-ODMCDASH V 1.1

CDASHUG 1.0

ICVs Q409CDASH-ODMCDASH V 1.1

CDASHUG 1.0

CDISC CONSENSUS PROCESSQ210

Q409

ReleasedQ2 10

CDASH-ODMCDASH V 1.1CDASHUG 1.0

ReleasedQ2 10

CDASH-ODMCDASH V 1.1CDASHUG 1.0

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/SASforClinicalDI.html

– Available with BASE/SAS

35

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

SUMMARY• Devices are important!

• Work is currently being done:– Review the 16 CDASH domains– Develop new domains

• New team members are welcome!

37

38

Contacts• Carey Smoak

– Team Leader

– Roche Molecular Systems, Inc.

– E-mail: carey.smoak@roche.com