SDTM Validation at Cephalon

1. SDTM Validation at Cephalon • Delaware Valley CDISC Users Network Meeting • May 11, 2009 • by Gary Cunningham

2. SDTM Domain XPT Files SDTM Supplemental XPT Files Cephalon Data Flow Cephalon/CDISC Standard (metadata repository) tabulations Raw Data Sets SDTM (-) Derived Data Sets SDTM and Analysis Clin Data Analysis XPT Files analysis Database Programming Study-level Metadata Clinical Programming

3. Cephalon/CDISC Standard (metadata repository) SDTM Domain XPT Files SDTM Supplemental XPT Files Cephalon SDTM Validation SDTM Validation SDTM Validation SDTM Validation tabulations Raw Data Sets SDTM (-) Derived Data Sets SDTM and Analysis Clin Data Analysis XPT Files analysis Database Programming Study-level Metadata Clinical Programming

4. Cephalon/CDISC Standard (metadata repository) Cephalon SDTM Validation SDTM Validation • Primarily focused on checking existing data as opposed to checking for gaps against SDTM model. • Various data checking / edit checking tools. • WebSDM • daily automated batch uploads into WebSDM across all ongoing studies • WebSDM errors are filtered and reports are sent to Database Programming. Raw Data Sets SDTM (-) Clin Data Database Programming

5. Cephalon/CDISC Standard (metadata repository) SDTM Domain XPT Files SDTM Supplemental XPT Files Cephalon SDTM Validation SDTM Validation SDTM Validation SDTM Validation tabulations Raw Data Sets SDTM (-) Derived Data Sets SDTM and Analysis Clin Data Analysis XPT Files analysis Database Programming Study-level Metadata Clinical Programming

6. Cephalon/CDISC Standard (metadata repository) Cephalon SDTM Validation SDTM Validation Derived Data Sets SDTM and Analysis Study-level Metadata Clinical Programming

7. Cephalon/CDISC Standard (metadata repository) Cephalon SDTM Validation SDTM Validation • Primarily focused on validation of single data set against SDTM (and Cephalon) standard during its “build”. • Each data set build program (via standard macros): • creates an ERROR and aborts the build if any SDTM (or Cephalon) Required or Expected variable is absent • creates an ERROR and aborts the build if Cephalon controlled terminology is not used (e.g. --TESTCD, --TEST, --SPID) • creates an ERROR and aborts the build if any value is truncated as a result of an insufficient length assignment in the metadata • creates a WARNING if any standard SDTM metadata is being overwritten by study-level custom metadata. • Other miscellaneous data checking tools. Derived Data Sets SDTM and Analysis Clinical Programming Study-level Metadata

8. Cephalon/CDISC Standard (metadata repository) SDTM Domain XPT Files SDTM Supplemental XPT Files Cephalon SDTM Validation SDTM Validation SDTM Validation SDTM Validation tabulations Raw Data Sets SDTM (-) Derived Data Sets SDTM and Analysis Clin Data Analysis XPT Files analysis Database Programming Study-level Metadata Clinical Programming

9. SDTM Domain XPT Files SDTM Supplemental XPT Files Cephalon SDTM Validation SDTM Validation Analysis XPT Files Clinical Programming

10. SDTM Domain XPT Files SDTM Supplemental XPT Files Cephalon SDTM Validation SDTM Validation • Primarily focused on validation of SDTM data sets as a whole • validation of data sets as a submission package against SDTM standard • includes validation checks across data sets. • WebSDM • complete set of SDTM data sets is loaded into WebSDM tool, validation report of structure and consistency errors is generated, and any data set issues are addressed • done at least two times: prior to database lock and after lock. • SUPP-- data sets are reattached to parent data sets and programmatically compared to original combined data sets. Analysis XPT Files Clinical Programming

11. Other Cephalon SDTM Validation • “Informal” SDTM data set validation: • throughout entire data flow • PROC FREQ within and across data sets (can be quite powerful!) • consistency checks across data sets • consistency checks across studies within the drug project • WebSDM-like checks • other miscellaneous checks.

12. Cephalon SDTM Validation Summary • Three-staged approach to SDTM validation: • Validation of Raw SDTM (-) data sets. • Validation of Derived SDTM data sets. • Validation of Derived SDTM data sets via submission transport files. • Validation “tools”: • Cephalon/CDISC Standard metadata repository • Derived data set build macros • WebSDM • other miscellaneous macros • custom SAS programs.

13. Comments on Validation • Three-staged approach to validation helps to ensure that both SDTM and Cephalon standards are followed. • Expectation is that the earlier validation will minimize problems later in the data flow process. • Validation is needed both within and across SDTM data sets; WebSDM tool provides some valuable checks across data sets that aren’t necessarily possible during individual SDTM data set development. • Using the WebSDM tool internally allows Cephalon to proactively address issues that FDA will find with its WebSDM checks. • However, • WebSDM “errors” should be taken into context as some WebSDM-defined “errors” may be insignificant or not represent real errors • WebSDM is one tool of many within the validation process and supplements the others, but does not replace them.

14. Questions / Contact Info • ? • Gary Cunningham • gcunning@cephalon.com