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Monika Kawohl Senior Statistical Programmer Accovion GmbH, Marburg, Germany CDISC based eSubmission Key Points of the CDISC SDTM/ADaM Pilot.

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Presentation on theme: "Monika Kawohl Senior Statistical Programmer Accovion GmbH, Marburg, Germany CDISC based eSubmission Key Points of the CDISC SDTM/ADaM Pilot."— Presentation transcript:

1 Monika Kawohl Senior Statistical Programmer Accovion GmbH, Marburg, Germany CDISC based eSubmission Key Points of the CDISC SDTM/ADaM Pilot

2 CDISC German UG Meeting 02-Sep Outline Coverage & Aim Process CDISC Model Specifics SDTM ADaM Define.xml FDA Reviewers Feedback Summary and Conclusions

3 CDISC German UG Meeting 02-Sep Coverage Legacy data conversion of 1 study to SDTM SDTM domains (SAS V5 XPT format) Annotated CRF ADaM datasets created from SDTM Analysis Results based on ADaM datasets All tied together via Metadata in define.xml eCTD structure but PDF TOC files

4 CDISC German UG Meeting 02-Sep Coverage - Pilot Submission Structure eCTD/eNDA hybrid: PDF TOCs, eCTD folders Source: Project Report – CDISC SDTM/ADaM Pilot

5 CDISC German UG Meeting 02-Sep Aim Verify interoperability of CDISC standards Obtain FDA reviewers feedback Provide implementation example Gap analysis of single CDISC Standards But... Not intended as guidance regarding Contents Process applied

6 CDISC German UG Meeting 02-Sep Process Source: Webcast – Results and Lessons from the CDISC SDTM/ADaM Pilot Project

7 CDISC German UG Meeting 02-Sep Process – Legacy Data Conversion Source-centric mapping specification QC of specifications before programming started Mapping via ETL Tool

8 CDISC German UG Meeting 02-Sep Process – SDTM/ADaM/define.xml SDTM without derived => ADaM => SDTM some derived Facilitates usage of derived data in SDTM review tools Lineage issue Explorative use - final decision pending Definition of metadata at specification level Prescriptive use of metadata reduces consistency issues (Suite of SAS macros used available to CDISC members) Concise computational algorithm descriptions No programs were submitted

9 CDISC German UG Meeting 02-Sep Process – Prescriptive Use of Metadata

10 CDISC German UG Meeting 02-Sep Process – Quality Control (QC) QC of specifications QC of programming/mapping against specifications Option: independent re-programming QC of Analysis Results against SAP QC of define.xml Verifying links and contents Verifying of technical requirements via tools Consistency via automated process based on metadata

11 CDISC German UG Meeting 02-Sep CDISC Model Specifics CDISC SDTM IG V3.1.1 CDISC SDTM V1.1 CDISC ADaM CDISC ADaM IG was not yet available (in preparation) CDISC CRT-DDS (define.xml) V1.0 CDISC ODM V1.3 for define.xml define.xml V1.0 standard based on ODM V1.2 Custom stylesheet Schema extension for ADaM part

12 CDISC German UG Meeting 02-Sep CDISC SDTM Specifics SDTM without derived Includes SDTM required derived variables, e.g., USUBJID, --BLFL, (--DY) SDTM with some derived Purpose: viewing derived data in standard domain structures Includes data derived in the ADaM creation step Population Flags (SUPPDM) AE Treatment Emergent Flag and MedDRA variables (SUPPAE) Endpoint Flag and Result Divided by UL of Normal Range (SUPPLB) Total Score as sum of single scores (New record in QS) ADaM => SDTM ensures consistency of derivation results

13 CDISC German UG Meeting 02-Sep CDISC ADaM Specifics Important since SDTM datasets not analysis-ready ADSL concept of ADaM V2.0 ADSL very helpful for all reviewers Baseline Characteristics Treatment Variables Population Flags Patient Completion Status Start and End of Study Drug, Date Patient was Last Observed All analysis datasets instead of datasets for key analyses At least Analysis Metadata could be limited to key results

14 CDISC German UG Meeting 02-Sep CDISC ADaM Specifics (Continued) Tracebility and transparency of analysis datasets Clear lineage from CRF to analysis Clear, unambigous metadata (computation methods) Include all CRF data + derived data Appropriate data selection via flags Facilitate reproduction of analysis results Allow for sensitivity analysis, test of robustness Sponsor-specific standards, e.g. variable names, PARAMs NOW available: Draft ADaM IG

15 CDISC German UG Meeting 02-Sep CDISC ADaM Concept Sample Selected variables from adqsadas.xpt SDTM reference Communication of analysis performed ADSL variables

16 CDISC German UG Meeting 02-Sep CDISC define.xml Specifics SDTM and ADaM metadata included in 1 define.xml file Facilitate links between SDTM and ADaM and vice versa Define.xml included in tabulations and analysis eCTD folder Navigation improved (define.pdf comparable) Framed version solves back button issue (IE specific)

17 CDISC German UG Meeting 02-Sep CDISC define.xml Specifics (Continued) Valuable sample for Analysis Metadata List of Analysis Results Standardized results description incl. links to Analysis output, underlying dataset, specifications (e.g. SAP) Layout not 100% consistent with new Draft ADaM documents

18 CDISC German UG Meeting 02-Sep Define.xml – Analysis Metadata Sample Link to CSR Table Link to Variable Metadata of ADSL Link to SAP Link to Analysis Metadata (s.b.)

19 CDISC German UG Meeting 02-Sep CDISC define.xml Specifics (continued) Deviations from Draft Metadata Submission Guidelines All derivations described via computation methods Separate column Comment column reserved for ADaM links to source datasets No Variable Value Level Metadata Limited to Controlled Terminology for test codes and names Controlled Terminology representation subdivided in Code Lists (Code and Decode) Discrete Value Listings Printing Issue

20 CDISC German UG Meeting 02-Sep CDISC define.xml Specifics Demo CDISC Pilot (Variable Metadata) CDISC Draft Metadata Submission Guidelines (Variable Metadata)

21 CDISC German UG Meeting 02-Sep CDISC define.xml Specifics Demo CDISC Pilot (Controlled Terminology) CDISC Draft Metadata Submission Guidelines (Value Level Metadata)

22 CDISC German UG Meeting 02-Sep FDA Reviewers Feedback Standard disclaimer (NOT the general FDA view) Overall, data were suitable for reviewers needs Value of SDTM depends on reviewers training status Use define.xml comments to explain CDISC jargon Integration of Reviewers Guide recommended ADaM essential since SDTM not Analysis-Ready ADSL variables, e.g. treatment in each dataset Derived variables in SDTM helpful Use of SDTM based review tools CAVEAT: Results may not be reproducible based on sole SDTM (additional analysis flags to be considered)

23 CDISC German UG Meeting 02-Sep FDA Reviewers Feedback (continued) Use of SDTM Review Tool WebSDM SDTM compliance check SDTM/define.xml consistency check Graphical Patient Profiles Merge of core variables (e.g. sex, treatment) to domains Merge of SUPPQUAL to parent domains Export of combined data to other tools Reviewers at time of Pilot more familiar with other tools

24 CDISC German UG Meeting 02-Sep FDA Reviewers Feedback (continued) Data documentation via define.xml Concept, Content, Navigation, Reviewers Guide Printing Sample for multiple-studies submission is missing FDA committed to standards Success of SDTM/ADaM depends on Training (implementers and reviewers) Experience (implementers and reviewers) Availability of suitable review tools

25 CDISC German UG Meeting 02-Sep Summary and Conclusions Overall, data were suitable for reviewers needs Very helpful implementation example No guidance => evolution of CDISC standards Importance of ADaM when submitting SDTM Familiarity with CDISC models is a key factor Implementer Reviewer Watch out for next pilot: multiple-studies safety data

26 CDISC German UG Meeting 02-Sep References CDISC SDTM/ADaM Pilot Project – Project Report (SDTMADaMPilotProjectReport.pdf) Slides from the CDISC Pilot Webcast (bmc_cdisc_sdtm-adam_pilot_v-2.pdf) Cathy Barrows presentation at CDISC EU IC 2008 (CDISC presentations website) Revised Pilot Submission Package as provided by CDISC (CDISC Members Only website)

27 Thank you! Questions?


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