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Copyright © 2008, SAS Institute Inc. All rights reserved.

SAS offers technology to facilitate working with CDISC standards : the metadata perspective.Mark Lambrecht, PhDPrincipal Consultant, Life SciencesSAS


Agenda

§ SAS actively supports CDISC standards

§ Tools’ approach (PROC CDISC, XML) : the foundation

§ Clinical DI : building the house• The industrial approach in CDISC mapping : clinical DI• Now that the metadata is gathered

§ What will SAS bring next ?


SAS actively supports CDISC standards


SAS and CDISC

§ SAS supports the effort to replace v5 xport file type with multiple modern, extensible XML file type

§ SAS is actively involved in multiple modeling committees:• SDTM, ADaM, Protocol, ODM, etc.

§ SAS has invested, and will continue to invest, in a variety of CDISC-enabling technologies


Delivery format : the old


Delivery format : the new


Tools approach : the foundation


XML

§ XML libname engine• Manipulating XML• ODM native mode• XML Mapper : mapping rectangular format to/from

hierarchical XML

§ XML conformance : 3 levels


SAS XML Libname Engine ODM Syntax

Load data from ODM XML into SAS data set

Declare input source

Declare output source

Save data from SAS data set into ODM XML

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PROC CDISC

§ Input CDISC ODM XML files to SAS data set(s)

§ Output SAS data set content to CDISC ODM XML

§ Validates CDISC SDTM content against model


PROC CDISC validation for SDTM

§ Verifies all required variables are present

§ Identifies dataset variables not defined in domain

§ Identifies missing, but expected, domain variables

§ Identifies missing, but permitted, domain variables

§ Verifies variables are of expected type and length

§ Identifies missing, but expected, controlled terminology (formats)


Proc CDISC Capabilities

§ Input CDISC ODM XML files to SAS data set(s)

§ Output SAS data set content to CDISC ODM XML

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Staying Current with Proc CDISC

§ http://www.sas.com/apps/demosdownloads/proccdisc_PROD_9_sysdep.jsp?packageID=000369

§ www.support.sas.com, then search on CDISC

Screenshot from 15-April-200815

http://www.sas.com/apps/demosdownloads/proc

http://www.support.sas.com


Proc CDISC Input Syntax for ODM

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Proc CDISC Output Syntax for ODM

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Proc CDISC for SDTM: Metadata Validation§ Verifies all required variables are present

§ Identifies dataset variables not defined in domain

§ Identifies missing, but expected, domain variables

§ Identifies missing, but permitted, domain variables

§ Verifies variables are of expected type and length

§ Identifies missing, but expected, controlled terminology (formats)

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Proc CDISC for SDTM: Data Validation

§ Verifies that required variables do not contain missing values

§ Identifies expected variables that contain missing values

§ Verifies conformance of all ISO-8601 specification assigned values

§ Notes correctness of yes/no and yes/no/null responses

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Proc CDISC Syntax for SDTM

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CDISC viewer


http://www.cs.utah.edu/~draperg/cartoons/jb/mainframe.html

http://www.cs.utah.edu/~draperg/cartoons/jb/mainframe.html


Clinical DI : building the house


Challenges

§ Globalization of reporting tools

§ Implementation of CDISC

§ EDC/CDMS system integration

§ More restrictive regulator demands

§ Data standardization

§ Validation

§ Integration of study-databases


§ CDISC models• Technology and tools need to support SDTM/ADAM model

− Version management– SDTM version

− Internal SDTM model enhancements− Submission driven transformation

– Define.xml

External drivers


Internal drivers

§ Cooperation• Structure of repositories

− Parent / Child• Exchange of programs• Exchange of skills• Global collection and managing of metadata• Transparency

− Visualization of data streams is possible− Reporting of metadata− SAS code is generated and can be viewed

• Security


SAS 9 platform


Clinical DI

§ Data Integration Server enables easy integrationof heterogenous clinical data into CDISC standards

§ SAS DI uses the Open Metadata Architecture

§ Using DI, individual programmer’s studyknowledge is documented in the metadata and made available for the whole organization


Operational Data

Analysis

Standardization

Validation

Aggregation

Submission

SAS Metadata Server

Impact of Metadata in Clinical Data Integration

Documents


Clinical DI

“Clinical DI brings the CDISC knowledge stored in peoples individual minds into a centralized IT environment, accessible for exploitation and decreasing the time needed for submission of clinical trial data”


Clinical DI Standardization Components § Folder structure

• Supports best practices• Based on SDTM IG 3.1.1• Includes:

− Controlled Terminology− Custom Domains− Model Classifications− Published Domains− Relationship Datasets− Trial Design Datasets

§ SDTM domain metadata• Published domains, Trial Design Domains, and relationship

datasets


SAS Data Integration Server

§ Visual Standardization Process

§ Drives relationships and associations

§ End up with standardized data AND specific metadata about how data was created


Clinical Data Integration Features Overview

§ SAS Management Console• Clinical DI Install/Update Plug-in• Study Manager Plug-in

§ DI Studio• Register Domains• SDTM Domain Designer• Suppqual Generator

§ Reports• Publish SDTM Library• Change Management Audit Report• SDTM Model Discrepancy• Model Analysis• Define.xml (beta)


SDTM Implementation Guide§ Centrally Accessible

§ Contains All Domains• General Purpose• Special-Purpose• Special-Purpose Relationship• Trial Design

§ Each Domain Contains• Table Structure• CDISC Table Level Metadata• CDISC Column Level Metadata

§ Allows For Custom Domain Expansion


Domain Level Metadata

SDTM Implementation Guide

Column Level Metadata (all columns)


Workflow and Change Management

§ Clinical DI components to support best practices in workflow:• Clinical Data Integration component installation and

administration• Setup a study and capture study metadata• Register domain to a study based on the standard

model definition• Generation of suppqual domains based on model

§ Metadata can be leveraged for reporting to support business process

§ Change management through user project folders


Study Manager

§ Registers repositories as studies

§ Stores basic study level metadata

§ Associates a SDTM version with the study

§ Drives consistency in using all Clinical DI plug-ins


CDISC Metadata Reporting is Domain Driven


PROC CDISC – CRT-DDS (Define.xml)

PROC CDISC DEFINE.XML

METATABLE

METACOLUMN

SUPPDOC

CRF

METHOD

VALUELIST


SAS Clinical Data Integration Benefits§ Positions the customer to build reusable data

management, analysis and reporting processes for clinical studies

§ Follows the CDISC STDM Implementation Guide v3.1.1 (and will support v3.1.2 when it is finalized). SDTM Model Verification.

§ Allows for flexibility and customizations necessary to implement SDTM+/-

§ Enables control and security using SAS Management Console

§ CDISC Metadata Reporting is Domain Driven

§ Change Management Auditing


PROC CDISC or Clinical DI ?

Complete technology for CDISC standarization and submission

Final conversion of rectangular SAS table/XML format

Primary objective

Explicit in metadata/DIImplicit in code, but complex to retrieve

Impact analysis

MediumNoneChange management

Globally accessibleinfrastructure

For use in local code developmentGlobally accessible ?

Can be attached to data or in external dictionary

Externally storedWhere are column mappings stored ?

High : Copy/Paste, Import/Export, Promotion/Replication, Parameterized processes, web services

Low to medium (macro’s)Re-usability

FastModerateSpeed of development

Clinical DIPROC CDISCTopic


PROC CDISC or Clinical DI ?

Fully customizable and standardreports provided

Only partiallySDTM data validation

Full automated access to metadata, including processes, infrastructure and external documents (CRF,…)

Partial ; more to come.CDISC metadata validation

Clinical DIPROC CDISCTopic

SAS Metamodel allows us to represent CDISC standards as “DeployedSoftware” that can be linked to studies\projects for integrated consistency

Difficult to manage and see what code used what version of CDISC models

Versions of CDISC standards/ internal

Well formed code, integrated documentation, synchronized transformations

Paper-based systemValidation of code


We did it before: implementation of clinical DI

§ Evaluation methodology : CDISC-readiness

§ Ingredients• Consultants :

− SAS Clinical DI and CDISC consultants and experts− Trained and recognized partners

• Technology• EDC, CDMS, relational databases, ERP, CTMS

§ Critical success factors

§ Risk analysis

§ Adaptation on CDISC metadata (SDTM+/-)

§ Value-level metadata, codelists, specific descriptions, custom domains, supplemental qualifiers


What will SAS bring next ?


Next version of PROC CDISC

§ ODM 1.2 and 1.3 read/write

§ Define.xml (CRT-DDS) 1.0.0 read/write

§ Validation for SDTM 3.1.1 and 3.1.2• Compliance checks• Custom checks• Available for 9.1.3 and 9.2


Next version of clinical DI Server brings you

§ A SAS-supported R&D solution

§ More complex and custom validation SDTM content and structure

§ CRT-DDS (define.xml) creation

§ CDISC Models, Version and Format support for Clinical DI Server

§ Controlled terminology

§ ADaM (2.0)

§ LAB, SEND, Protocol Representation, CDASH


SAS Universal Viewer

§ Will replace CDISC viewer and will support all CDISC file formats

§ Hierarchical and tabular formats viewing


New ISO8601 formats in base SAS 9.2

§ New series for writing, reading ISO8601 dates, times and *new* intervals (duration).


§ Committed to bringing you CDISC tools and full solutions

§ Continuous R&D effort

§ Working together with customer because of many CDISC-trained consultants and partners in the field

§ Domain knowledge and industry advisory role