1. Updates on CDISC Standards Validation
NJ CDISC User Group
September 19, 2013

2. Topics CDISC standards validation initiative FDA update on SEND checks
OpenCDISC v1.4.1 release
OpenCDISC plans

3. CDISC validation projects
Past
ADaM validation checks
Define.xml tool (schema only)
CAB project
Current plan (CDISC Intrachange 2013)
Each CDISC development team will create a comprehensive list of business rules as a supplement to their standards
Rationale
Standards developers are the best experts in defining standards compliance requirements

4. CDISC ADaM Validation Checks
First v1.0 was introduced in
Current v1.2 was released on
v1.2 includes 244 checks based on ADaM IG text
ADSL and BDS data only
Today the team is planning 2 iterations
update existing checks and create new checks for ADAE, ADTTE data
update checks after a new release of ADaM IG

5. Define.xml XML Schema Validation for Define.xml v1.0, 2009-11
Validator for Define.xml schema,
Define.xml v2.0 includes many business rules embedded in standard specifications
Today the team is working on detailed list of validation rules
Executable specification will be published as Schematron

6. SDTM and SEND CAB/VP project, 2010 Current plan:
Evaluated compliance rules for SDTM/define.xml
Reviewed checks across different vendors
Current plan:
Create comprehensive list of business rules as a supplement to new standards. E.g., SDTM v3.1.5, TA standards, etc.
Challenges:
Extra resources are needed
Synchronization across teams
Exact project scope and format are still under discussion

7. FDA’s validation rules for SEND data
FDA Rule number
MESSAGE
DESCRIPTION
DOMAINS
SEVERITY
NONCLIN-0006
Invalid variable name. Variable names in the domain datasets should be compliant with the SEND standard
Only variable names listed in the SENDIG Version 3.0 should be used in a domain dataset.
ALL
Error
NONCLIN-0007
Invalid format for TEDUR. The variable value values must conform to the ISO 8601 international standard
The variable values for all timing variables must conform to the ISO 8601 international standard TE
NONCLIN-0008
Invalid format for RFSTDTC. The variable value values must conform to the ISO 8601 international standard DM
NONCLIN-0009
Invalid format for RFENDTC. The variable value values must conform to the ISO 8601 international standard

8. Off-Topic: FDA’s Position Statement
Study Data Standards for Regulatory Submissions
FDA recognizes the investment made by sponsors over the past decade to develop the expertise and infrastructure to utilize Clinical Data Interchange Standards Consortium (CDISC)[1] standards for study data. The submission of standardized study data enhances a reviewer’s ability to more fully understand and characterize the efficacy and safety of a medical product.
The Prescription Drug User Fee Act (PDUFA V)[2] Performance Goals state that FDA will develop guidance for industry on the use of CDISC data standards for the electronic submission of study data in applications. In the near future, FDA will publish guidance that will require study data in conformance to CDISC standards.[3]
FDA envisions a semantically interoperable and sustainable submission environment that serves both regulated clinical research and health care. To this end, FDA will continue to research and evaluate, with its stakeholders, potential new approaches to current and emerging data standards. FDA does not foresee the replacement of CDISC standards for study data and will not implement new approaches without public input on the cost and utility of those approaches.  
September 13, 2013

9. OpenCDISC v1.4.1 release,
Bug fixes, enhancements, but no global changes
Support for QS Terminology
CDISC CT checks for extensible codelists are Informational and independent from user’s codelists in Define.xml
SDTM with all applicable checks
Simplified, consistent and concise error messages and rule descriptions
Excel report includes versions of Validator, CT, and MedDRA
Enhancement to check definition syntax

10. SDTM Terminology
New CDISC Control Terminology checks based on CT rather than on outdated SDTM IG assignments
PKUNIT instead of UNIT in PC and PP domains
PKPARM, SCTEST, etc.
QS Terminology (CT0100-CT0255 checks)
CT 1:1 consistency checks for paired variables
TSPARM/TSPARMCD, EGTEST/EGTESTCD, etc.
Terminology checks on non-extensible codelists were changed to Errors
CT0001 (ACN), CT0002 (AESEV), CT0030 (RELTYPE), CT0059 (NY), etc.

11. Examples of SDTM checks “tuning”
Rule SD0006 (“No baseline results”) was modified to exclude NOTASSGN subjects
Rules SD0026 and SD0029 (“units are required”) were modified to exclude PH, SPGRAV and all Antibody lab tests
Rule SD0037 (data vs. user’s codelist) was modified to exclude EGORRES variable
Rule SD0069 (“No Disposition record for subject”) was modified to exclude SCRNFAIL and NOTASSGH subjects
Rule SD1037 (“Missing value for --TOX, when --TOXGR is populated”) was modified to ignore records with TOXGR=0

12. SEND specific
Fixed incorrect variable labels and order of variables in domains
Several Check ID replacement for consistency with SDTM checks
CT1003-> CT0088, CT1004->CT0089, etc.

13. ADaM Checks compliant with ADaM Validation Checks 1.2
Change all consistency rules to only run when primary variables are populated
Remove AD Expected variable is not present within dataset.  This is not a real rule.  It was copied from SDTM logic
Changes to improve label validation (AD0018)
Addition of other rules interpreted from IG, which were not released by CDISC team

14. OpenCDISC v2.0 Date of release is planned for 2013Q4
Support for Define.xml v2.0
Metadata driven
Specifications based on Define.xml v2.0 format
Validation organized by functional area. E.g.,
SDTM Compliance
Control Terminology
Metadata
Regulatory Specific
Data Quality

15. Example of metadata driven checks
SD1117 “Duplicate records” in Findings domain
The “generic” check uses 10 Key Variables
USUBJID
ESTCD
--CAT
--SCAT
--METHOD
--SPEC
--DRVFL
--EVAL
VISITNUM
--TPTNUM

16. Key variables as defined in SDTM IGIE
STUYID, USUBJID, IETESTCD LB
STUDYID, LBTESTCD, LBSPEC, VISITNUM, LBTPTREF, LBTPTNUM QS
STUDYID, USUBJID, QSCAT, QSTESTCD, VISITNUM, QSTPTREF, QSTPTNUM DA
STUDYID, USUBJID, DATESTCD, DADTC FA
STUDYID, USUBJID, FAOBJ, VISITNUM, DATPTREF, FATPTNUM TU
STUDYID, USUBJID, TULINKID, TUTESTCD, TUSTRESC, (TULOC, TULAT, TUDIR, TUMETHOD), TUEVAL, VISITNUM
SDTM IG: “Note that the key variables shown in this table are examples only.
A sponsor‘s actual key structure may be different.”

17. Combined Key variables
STUDYID
USUBJID
POOLID
--LNKID
--SPID
--TESTCD
--OBJ
--ORRES
--CAT
--SPEC
--LOC
--DIR
--LAT
--METHOD*
--DRVFL*
--ANTREG
VISITNUM
--DTC
--ENDTC
--TPTREF
--TPTNUM
* added by OpenCDISC as common cases in actual study data

18. The check implementation options
Generic check with 20 key variables?
Separate check for each domain?
v.2.0 approach
Take domain key variables from Standard metadata
If define.xml is available, then utilize key variables provided in Study metadata
Compare Standard and Study key variables

19. OpenCDISC Network
More direct involvement in OpenCDISC project development process
Beta testing
Requirements input
Additional resources for new projects
Better support
Face-to-face meetings with users
Webinars
Training and sharing users experience
First meeting is before CDISC Interchange 2013

20. References CDISC ADaM resources CDISC define.xml resources
CDISC define.xml resources
FDA Study Data Standards Resources
OpenCDISC

21. Questions/Feedback Sergiy Sirichenko sergiy@opencdisc.org
Max Kanevsky
Mike DiGiantomasso