Creating Define-XML version 2 including Analysis Results ...€¦ · Creating Source Metadata for Define -XML v2 • %define_createsrcmetafromsaslib - derives . initial . source metadata

Copyr i g ht © 2014, SAS Ins t i tu t e Inc . A l l r ights reser ve d .

Creating Define-XML version 2 including Analysis Results Metadata

with the SAS® Clinical Standards ToolkitLex Jansen

Principal Software Developer @ SAS

PharmaSUG 2016

Copyright © 2014, SAS Institute Inc. All rights reserved.

Agenda

Why Analysis Results Metadata?

Analysis Results Metadata in Detail

SAS Support for 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

Why Analysis Results Metadata ?


ADaM Results Metadata v1 for Define-XML v2






2005 - CRT-DDS v1.0Focus on SDTM metadata

2008 - CDISC SDTM/ADaM Pilot Project

2009 - ADaM v2.1 Model ADaM specific metadata requirements(Parameter VLM, Analysis Results Metadata)

2009 - CDISC/FDA Integrated Data Pilot2013 - Updated CDISC SDTM/ADaM Pilot

2013: Define-XML v2.0officially applicable for ADaM)2015 - Analysis Results Metadata v1.0 for Define-XML v2

Including draft Analysis Results Metadata

based on CRT-DDS v1.0)

Including draft Analysis Results Metadata

based on CRT-DDS v1.0)

ADaM Metadata and Define-XML History


ADaM Results Metadata – Pilot 1 (2008)


ADaM Results Metadata – Pilot 2 (2009)


ADaM Results Metadata – Pilot 1 Update (2013)


• 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

ADaM Results Metadata – Pilots


ADaM Results Metadata – 3 Pilots – 3 XML formats






• Formal Technical Specifications



• 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



ADaM Results Metadata v1 for Define-XML v2ODM

Study

GlobalVariables

MetaDataVersion

def:SupplementalDoc

def:ValueListDef

def:WhereClauseDef

ItemGroupDef

ItemDef

CodeList

MethodDef

def:CommentDef

def:leaf

arm:AnalysisResultDisplays


• 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



PMDA – New Study Data Technical Conformance Guide (April 27, 2015) *

* PMDA Technical conformance guide (in Japanese) http://www.pmda.go.jp/files/000204728.pdfProvisional Translation (as of July 2015) http://www.pmda.go.jp/files/000206449.pdf

• 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.


http://www.pmda.go.jp/files/000204728.pdf

http://www.pmda.go.jp/files/000206449.pdf


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 1.7.1 – HotFix)

• FDA reference in the Data Standards Catalog?



Analysis Results Metadata for Define-XML v2in Detail


• 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

ADaM Results Metadata in the ADaM Model (2009)
























SAS Support for Analysis Results Metadata for Define-XML v2


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



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)



Introduction

• Supported CDISC standards in Toolkit 1.7:• SDTM 3.1.2, 3.1.3 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, 1.3.1 - Read / Write / Validate

• NCI CDISC Controlled Terminology (June 2014)

(import/export of ODM XML through CT 1.0 standard)



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

2.0.0 standard

• CST 1.7.1 expected availability May/June 2016.

• CST is available at no additional charge to currently

licensed SAS customers.

• Contact your SAS Account Representative concerning

availability



SAS Clinical StandardsToolkit 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


SAS Clinical Standards

Toolkit 1.7.1SAS Data Model for Define-XML


Define.xml

cube

39 Define-XMLSAS data sets

XML Map

JavaObj

JavaObj

Data _null_

SAS Clinical Standards Toolkit and Define-XML - Process Flow

7 Source MetadataSAS data sets



Toolkit 1.7.1From Study Source Metadata to Define-XML v2

Internal SAS representation of

Define-XML

(54 SAS data sets*)

StudyMetadata

Table Metadata

Column Metadata

Value Level Metadata

CodelistMetadata

Document Metadata

Analysis Results

Metadata

XMLValidation Process

*Define-XML v2 uses 39 data sets



Toolkit 1.7.1From Study Source Metadata to Define-XML v2



Toolkit 1.7.1

Creating Source Metadata for Define-XML v2:Mapping your Metadata

Internal SAS representation of Define-XML

StudyMetadata

Table Metadata

Column Metadata

Value Level

Metadata CodelistMetadata

Document Metadata

Analysis Results

Metadata

Excel

MDR



Toolkit 1.7.1

Source Metadata - source_study- One record per study

ADaM example



Toolkit 1.7.1

Source Metadata - source_tables- One record per table



Toolkit 1.7.1

Source Metadata - source_columns- One record per table, column



Toolkit 1.7.1

Source Metadata - source_values- One record per table, column, whereclause



Toolkit 1.7.1

WhereClausesSyntax defined with Railroad DiagramChecked in CST with a Regular Expression



Toolkit 1.7.1

WhereClausesSyntax defined with Railroad DiagramChecked in CST with a Regular Expression



Toolkit 1.7.1

Source Metadata - source_codelists- One record per CodeList, Item



Toolkit 1.7.1

Source Metadata - source_analysisresults (ADaM)- One record per DisplayIdentifier, ResultIdentifier, Table



Toolkit 1.7.1

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.



Toolkit 1.7.1Source Metadata - source_documents (ADaM)- One record per table, column, whereclauseor- One record per DisplayIdentifier, ResultIdentifier



Toolkit 1.7.1Creating 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)



Toolkit 1.7.1Define-XML v2 with Analysis Results Metadata

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Creating Define-XML version 2 including Analysis Results ...€¦ · Creating Source Metadata for Define -XML v2 • %define_createsrcmetafromsaslib - derives . initial . source metadata