MANAGING AND ANALYZING CLINICAL DATA MARK LAMBRECHT, PRINCIPAL INDUSTRY CONSULTANT, SAS BIAS MEETING, MARCH 14TH 2014, MILAN, ITALY. C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . TABLE OF CONTENTS • SAS and CDISC • Clinical trial challenges • The promise for CDISC • SAS response • PROC CDISC, SAS Clinical Standards Toolkit, SAS Clinical Data Integration • Roadmap and SAS destination • Capabilities and processes supported by SAS • Examples • Roundtrip in define.xml • Reading a define.xml • ADaM support • Bulk metadata manipulation C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . THE CLINICAL TRIAL CHALLENGES … With the growth of industry standards, the level of complexity increases. SDTM QS Supplements The expected trend is continued increase of complexity. Content Standards Semantics Technical Standards Therapeutic Areas Parkinson’s Disease BRIDG v3.0.3 SDTM v1.2 SDTM IG v3.1.2 CDASH v1.0 SDTM v1.1 SDTM IG v3.1.1 SDTM v1.0 BRIDG ODM SDTM IG v1.1 v1.3 v3.1 Define.xml v1.0 ODM ODM v1.2.1 v1.1 / ODM BRIDG ADaM v1.2 v1.0 v2.0 2002 2005 2003 2006 2004 2007 C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . BRIDG v2.1 BRIDG v2.0 ADaM v2.1 ADaM IG v1.0 BRIDG v3.0 SDTM v3.1.2 Am.1 ADaM Val. Checks v1.0 Alzheimer v1.0 BRIDG v3.0.2 SDM.XML v1.0 ODM v1.3.1 BRIDG v3.0.1 BRIDG v1.1.1 BRIDG v2.2 Protocol Model v1.0 2008 2009 2010 ADaM Val. Checks v1.1 Oncology Diabetes BRIDG UG v2 Define.xml v2.0 PKD BRIDG v3.2 SDTM v1.4 SDTM IG v3.1.4 Tuberculosis Schizophrenia ADaM MD Guide CDASH v1.2 SDTM v1.3 SDTM IG v3.1.3 Therapeutic Brain Injury VirologyHepatitis C Devices ADaM Val. Checks v1.2 Cardiovascular CDASH E2B SAE IG BRIDG v4.0 Virology … SDTM Associated Persons IG v1.0 SEND v3.0.1 Asthma Multiple Sclerosis Define.xml IG Validation CDASH v2.0 SDTM v1.5 SDTM IG v3.1.5 ADaM General Occurrence Model v1.0 ADaM Integration IG v1.0 Extended ODM PRM XML Schema Pain PRM Toolset v1.0 CDASH v1.1 CDASH UG v1.0 SEND v3.0 2011 Alzheimer v1.1 SDTM.xml v1.0 ADaM IG v1.1 SEND v3.1 SDTM Devices IG v1.1 BRIDG v3.1 Protocol Concept Guide SDTM Device Submission Pilot 2012 2013 2014 CDISC A BUSINESS CASE BY GARTNER AND CDISC C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . SAS RESPONSE C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . • PROC CDISC : SAS first attempt to support CDISC standards • SAS Clinical Standards Toolkit • SAS Clinical Data Integration, SAS Drug Development CLINICAL RESEARCH INFORMATION FLOW SAS Dictionary coding (TMS) EDC (Rave) EDC (Other) Submission data sets SDTM ADaM Others Adapters / Interfaces ePRO and others Adapters / Interfaces Internal systems Adapters / Interfaces Labs and other external sources Raw data Real-world data External metadata (RDF, OWL, etc.) Raw data C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . SAS Clinical Data Integration Metadata, integration and standardization management SAS Drug Development Metadata Tables, figures and listings Data and analytics platform Pooled analyses JMP Clinical Patient Profiles/ Medical Review SAS Visual Analytics Exploration across and beyond trials Transparency initiatives PROC CDISC • • • • • Still supported in SAS 9.4, but stable Support for reading ODM 1.2 and SDTM 3.1 Not flexible enough for custom domains, or for changing standard domains. No library concept – everything built-in in code Advise against deployment and replace by novel SAS technologies C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . SAS CST SAS CLINICAL STANDARDS TOOLKIT • • • • • The SAS Clinical Standards Toolkit (SAS CST) provides SAS implementation of evolving clinical standards and provide a framework that exploits these standards to meet common clinical research analysis and submission requirements. SAS CST provides support both for CDISC and non-CDISC general clinical standards Support for SAS table and XML files Some Java and XLST inside to manage XML files. SAS Clinical Standards Toolkit 1.6 : released February 2014 based on SAS 9.4 C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . SAS CDI SAS CLINICAL DATA INTEGRATION SAS Clinical Data Integration is a data transformation solution designed to help companies organize, standardize and manage their clinical research data and metadata. The solution enables companies to Integrate data from disparate sources Integration with EDC systems, e.g. Medidata Rave Standardize their in-process data to industry models Migrate legacy data to modern standard models Leverage standardized data to efficiently prepare data for analysis and submission to regulatory authorities. • Is targeted for both SAS programmers and clinical data managers • SAS Clinical Standards Toolkit “under the hood” • SAS Clinical Data Integration capabilities now integrated in SAS Drug Development with code that is generated in SAS CDI can be executed straight from SAS Drug Development C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . Protocol Design Data Capture to Data Analysis CONVERSION Compound Info Life Cycle REPOSITORY SAS Life Science Analytics Framework EDC/CDMS C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . Data Quality Service Detailed Data Store, Metadata Store SAS LIFE SCIENCE ANALYTICS FRAMEWORK A NEW FRAMEWORK FOR CLINICAL TRIAL ANALYTICS Primary Platform • Shared repository • Licensing • Single identity • Hosting model • Partner collaboration • Access & audit trail C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . Analysis & Regulatory Controls Data Standards Repository Workflow Study & standards metadata Information Management Operations & Optimization Other SAS Offerings Mapping Risk based scoring and monitoring Visual Analytics Compliance Import/export metadata Instance data standards Post marketing & safety surveillance Data Transparency Analysis processes Connects protocol/study design Integration (EDC, Safety, ePRO, etc.) Site selection/ management Enterprise Miner Process traceability Manage controlled terminology Data traceability/ lineage Patient recruitment others SAS & CDISC END-TO-END IN CDISC Data models Metadata Macro API library and customization C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . Validation / Adherence checks SAS code generation SAS & CDISC END-TO-END IN CDISC : SAS CST 1.6 AND SAS CDI 2.5 SEND 3.0 standard support Integration with Medidata Rave / EDC Cus tom domain promotion and standards govern an ce Incremental and granular standards update in SAS CDI SDTM up to 3.2 (SDTM 1.4 IG) ADaM support 2.1 updates ODM 1.3.1 support Extract Clinical and Reference data into SAS datasets Validate Toolkit metadata CRT-DDS 1.0 support Import and export define.xml files Import ADaM, SDTM and SEND information from define.xml SDTM up to 3.2 (SDTM 3.1.4 IG) Controlled terminology support Define-XML 2.0 support SAS Clinical Standards Toolkit Code runs everywhere SAS Clinical Data Integration C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . Updates to macro framework Full UTF-8 and S-JIS code support DEFINE.XML ROUND TRIP Sponsor •Compares results to study specifications Sponsor • Extracts metadata from implemented define.xml file DEFINE.XML Data Management Team(CRO) • Produces define.xml based on implementation C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . Sponsor • Creates define.xml based on study specifications Data Management Team(CRO) • Extracts metadata from define.xml file Data Management Team(CRO) • Implements and populates domains READING THE SAS CLINICAL STANDARDS TOOLKIT DEFINE.XML Source_*.sas7bdat %crtdds_read DEFINE.XML %sdtmutil_create Src Meta From CRTDDS %sdtmutil_ Create Formats From CRTDDS SAS representation of CRT-DDS C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . %cstutil_create Tables From Metadata Code List SAS Format Catalog zero observation Domain data sets READING THE SAS CLINICAL DATA INTEGRATION DEFINE.XML C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . ADAM SUPPORT CDI 2.4 C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . BULK METADATA MANIPULATION CDI 2.4 C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . GOAL • SAS provides you with a complete technology and solution framework, not just to use CDISC standards, but to manage and generate clinical standards data with the aim to visualize, analyze, submit, and ensure high qualityclinical data C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d . VISUALIZATION C op yr i g h t © 2 0 1 3 , S A S I n s t i t u t e I n c . A l l r i g h t s r es er v e d .