Creating Define-XML version 2 including Analysis Results Metadata with the SAS Clinical Standards Toolkit

Transcription

1 Creating Define-XML version 2 including Analysis Results Metadata with the SAS Clinical Standards Toolkit Lex Jansen Principal Software SAS PharmaSUG 2016

2 Agenda Why Analysis Results Metadata? Analysis Results Metadata in Detail SAS Support for Analysis Results Metadata

3 Why Analysis Results Metadata? Traceability is a fundamental principle in ADaM: It enables the reader to understand the data flow from collection to SDTM and ADaM to Analysis Results Analysis Results Metadata provides traceability from results in a statistical display to the data in the analysis datasets Analysis Results Metadata includes: Identification of critical analysis displays and particular results Details on analysis performed (reason, underlying analysis dataset(s), analysis variables, selection criteria, documentation, programming statements) Facilitates documentation and reproduction of the analysis results Not needed - or advisable - for every analysis in a submission

4 ADaM Results Metadata v1 for Define-XML v2

5 ADaM Results Metadata v1 for Define-XML v2

6 ADaM Results Metadata v1 for Define-XML v2

7 ADaM Metadata and Define-XML History CRT-DDS v1.0 Focus on SDTM metadata CDISC SDTM/ADaM Pilot Project Including draft Analysis Results Metadata based on CRT-DDS v1.0) ADaM v2.1 Model ADaM specific metadata requirements (Parameter VLM, Analysis Results Metadata) CDISC/FDA Integrated Data Pilot Updated CDISC SDTM/ADaM Pilot Including draft Analysis Results Metadata based on CRT-DDS v1.0) 2013: Define-XML v2.0 officially applicable for ADaM) Analysis Results Metadata v1.0 for Define-XML v2

8 ADaM Results Metadata Pilot 1 (2008)

9 ADaM Results Metadata Pilot 2 (2009)

10 ADaM Results Metadata Pilot 1 Update (2013)

11 ADaM Results Metadata Pilots No formal specification Draft XML schemas (or no schema at all) Based on CRT-DDS 1.0 (Define-XML 1.0) Limited document referencing capabilities No WhereClause support Limited comment support

12 ADaM Results Metadata 3 Pilots 3 XML formats

13 ADaM Results Metadata v1 for Define-XML v2

14 ADaM Results Metadata v1 for Define-XML v2

15 ADaM Results Metadata v1 for Define-XML v2 Formal Technical Specifications

16 ADaM Results Metadata v1 for Define-XML v2 For Define-XML v2 only Utilizes various Define-XML v2 constructs WhereClause Document reference support Comment support It is recommended to move to Define-XML v2

17 ADaM Results Metadata v1 for Define-XML v2 ODM Study GlobalVariables MetaDataVersion def:supplementaldoc def:valuelistdef def:whereclausedef ItemGroupDef ItemDef CodeList MethodDef def:commentdef def:leaf arm:analysisresultdisplays

18 ADaM Results Metadata v1 for Define-XML v2 Updated Define-XML v2 XSL Stylesheet Works for ADaM, SDTM, SEND (with or without Results Metadata) Bug fixes Many improvements for linking to external PDF documents with physical page references or named destinations

19 ADaM Results Metadata v1 for Define-XML v2 PMDA New Study Data Technical Conformance Guide (April 27, 2015) * In order for the review of clinical study data to progress smoothly, it is important that the relationship between the analysis results shown in the application documents and the analysis datasets is easily understandable. Therefore, the definition documents of the ADaM datasets should preferably include Analysis Results Metadata... For the format of the Analysis Results Metadata, the applicant should refer to the Analysis Results Metadata Specification for Define-XML by CDISC to the extent possible, but if it is difficult to include it into the definition document, it is possible to submit it as a separated file in PDF format. * PMDA Technical conformance guide (in Japanese) Provisional Translation (as of July 2015)

20 ADaM Results Metadata v1 for Define-XML v2 What s Next? The ADaM Metadata Team is developing validation checks for The Analysis Results Metadata extension These can then be implemented by validating applications (Pinnacle 21,...) But you can already validate your Define-XML v2 (+ ARM) against the XML Schema (you should!) Implementations (SAS Clinical Standards Toolkit HotFix) FDA reference in the Data Standards Catalog?

21 Analysis Results Metadata for Define-XML v2 in Detail

22 ADaM Results Metadata in the ADaM Model (2009) Display Identifier Display name Result Identifier Parameter (Code/Decode) Analysis Variable Reason Dataset Selection Criteria Documentation Programming Statements * Version 2.1 of the Analysis Data Model (ADaM) Document, December 17, 2009

23 ADaM Results Metadata v1 for Define-XML v2

24 ADaM Results Metadata v1 for Define-XML v2

25 ADaM Results Metadata v1 for Define-XML v2

26 ADaM Results Metadata v1 for Define-XML v2

27 ADaM Results Metadata v1 for Define-XML v2

28 ADaM Results Metadata v1 for Define-XML v2

29 ADaM Results Metadata v1 for Define-XML v2

30 ADaM Results Metadata v1 for Define-XML v2

31 ADaM Results Metadata v1 for Define-XML v2

32 ADaM Results Metadata v1 for Define-XML v2

33 ADaM Results Metadata v1 for Define-XML v2

34 SAS Support for Analysis Results Metadata for Define-XML v2

35 SAS Clinical Standards Toolkit 1.7 Introduction Framework to primarily support Clinical Research activities (CDISC). Designed as an integral part of Clinical Data Integration (CDI) Available to all licensed SAS customers as open source SAS Macros and metadata at no additional charge. Framework: designed to customize and extend

36 SAS Clinical Standards Toolkit 1.7 Introduction A collection of metadata and "tools", providing an initial set of standards and functionality that is evolving and growing with updates and releases. Provides SAS representation of published standards as SAS data sets and catalogs Contents standards: SDTM, ADaM, SEND XML standards: Define-XML, Dataset-XML and ODM Controlled Terminology (CDISC/NCI)

37 SAS Clinical Standards Toolkit 1.7 Introduction Supported CDISC standards in Toolkit 1.7: SDTM 3.1.2, and 3.2 ADaM 2.1 (ADSL, Basic Data Structure, ADAE and ADTTE) CDASH 1.1 Domain definitions SEND 3.0 (initial implementation) CRT-DDS 1.0 (Define-XML - Create / Import / Validate) Define-XML 2.0 (Create / Import / Validate) Dataset-XML 1.0 (Create / Import / Validate) ODM 1.3.0, Read / Write / Validate NCI CDISC Controlled Terminology (June 2014) (import/export of ODM XML through CT 1.0 standard)

38 SAS Clinical Standards Toolkit 1.7 Introduction Hotfix for Toolkit 1.7 (CST 1.7.1): Support for Analysis Results Metadata v1.0 for Define-XML v2 Implemented as an update to the existing CDISC-DEFINE-XML standard CST expected availability May/June CST is available at no additional charge to currently licensed SAS customers. Contact your SAS Account Representative concerning availability

39

40 SAS Clinical Standards Toolkit 1.7 SAS Data Model for Define-XML SAS Clinical Standards Toolkit v1.7 provides a data model that represents the Define-XML v2 format in SAS data sets Patterned to match the XML element and attribute structure of the ODM XML format XML element table XML attribute column

41 SAS Clinical Standards Toolkit SAS Data Model for Define-XML

42 SAS Clinical Standards Toolkit and Define-XML - Process Flow JavaObj Define.xml XML Map JavaObj cube Data _null_ 39 Define-XML SAS data sets 7 Source Metadata SAS data sets

43 SAS Clinical Standards Toolkit From Study Source Metadata to Define-XML v2 Column Metadata Value Level Metadata Codelist Metadata Table Metadata Document Metadata Study Metadata Internal SAS representation of Define-XML Analysis Results Metadata XML Validation Process (54 SAS data sets*) *Define-XML v2 uses 39 data sets

44 SAS Clinical Standards Toolkit From Study Source Metadata to Define-XML v2

45 SAS Clinical Standards Toolkit Creating Source Metadata for Define-XML v2: Mapping your Metadata MDR Excel Table Metadata Column Metadata Value Level Metadata Codelist Metadata Document Metadata Study Metadata Analysis Results Metadata Internal SAS representation of Define-XML

46 SAS Clinical Standards Toolkit Source Metadata - source_study - One record per study ADaM example

47 SAS Clinical Standards Toolkit Source Metadata - source_tables - One record per table

48 SAS Clinical Standards Toolkit Source Metadata - source_columns - One record per table, column

49 SAS Clinical Standards Toolkit Source Metadata - source_values - One record per table, column, whereclause

50 SAS Clinical Standards Toolkit WhereClauses Syntax defined with Railroad Diagram Checked in CST with a Regular Expression

51 SAS Clinical Standards Toolkit WhereClauses Syntax defined with Railroad Diagram Checked in CST with a Regular Expression

52 SAS Clinical Standards Toolkit Source Metadata - source_codelists - One record per CodeList, Item

53 SAS Clinical Standards Toolkit Source Metadata - source_analysisresults (ADaM) - One record per DisplayIdentifier, ResultIdentifier, Table

54 SAS Clinical Standards Toolkit Source Metadata - source_analysisresults (ADaM) - One record per DisplayIdentifier, ResultIdentifier, Table Whitespace and "\n" or Carriage Return ('0D'x) in Code metada will be honored in Define-XML file and HTML display.

55 SAS Clinical Standards Toolkit Source Metadata - source_documents (ADaM) - One record per table, column, whereclause or - One record per DisplayIdentifier, ResultIdentifier

56 SAS Clinical Standards Toolkit Creating Source Metadata for Define-XML v2 %define_createsrcmetafromsaslib - derives initial source metadata files from a data library that contains SAS study domain data sets. Uses SDTM/ADaM/SEND standards metadata to fill in gaps. Can not create study metadata like: Origin, Derivation, Comment, Value Level Metadata %define_createsrcmetafromdefine - derives source metadata files from a data library that contains the SAS representation from Define- XML V2.0 file, imported via %define_read. %cstutilmigratecrtdds2define - migrates source metadata data sets from CRT-DDS v1.0 to Define-XML v2.0 %cstutilgetncimetadata - create the source_codelists dataset from a list of format catalogs that define the study formats a SAS data set that contains CDISC/NCI codelist metadata (imported from CDISC/NCI ODM XML file)

57 SAS Clinical Standards Toolkit Define-XML v2 with Analysis Results Metadata

58 Thank You! Questions?