An Introduction To CDISC
An Introduction to CDISC:Available CDISC Standards andModels and How SAS Supports TheseDave HandelsmanPrincipal Strategist, Clinical R&D, SASOctober 2005Copyright 2005, SAS Institute Inc. All rights reserved.
Agenda Part I: What is CDISC and Why Standards? Part II: Available CDISC Standards andModels and How SAS Supports These Part III: CDISC Collaborations and Standards inProgressCopyright 2005, SAS Institute Inc. All rights reserved.2
Copyright 2005, SAS Institute Inc. All rights reserved.3
Clinical Data Interchange Standards ConsortiumCDISC is an open, multidisciplinary, non-profit organizationcommitted to the development of worldwide industrystandards to support the electronic acquisition,exchange, submission and archiving of clinical trialsdata and metadata for medical and biopharmaceuticalproduct development.The mission of CDISC is to develop and support global,platform-independent data standards that enableinformation system interoperability to improve medicalresearch and related areas of healthcare.Copyright 2005, SAS Institute Inc. All rights reserved.4
CDISC Standards Operational Data Model (ODM) Submission Domain Standard (SDS) Study Data Tabulation Model (SDTM) Standard for Exchange of Non-clinical Data(SEND) Analysis Data Model (ADaM) Laboratory Data Model (Lab) Case Report Tabulation Data Definition Specification(CRTDDS - aka define.xml) Protocol Representation Standard Biomedical Research Integrated Domain Group(BRIDG)Copyright 2005, SAS Institute Inc. All rights reserved.5
ODM – Operational Data Model Written in XML Clinical trials data recording / transfer / archive Contains both study metadata and clinical dataModel Features: Framework can be used by any clinical data management(CDM) system or clinical application Supports 21 CFR Part 11 audit trail and electronic signaturesSupports archiving & data retention guidanceProvides for incremental transfersIncludes vendor extension capabilityCopyright 2005, SAS Institute Inc. All rights reserved.6
Interchange cycle – move to ODMSponsorHelper Traditional approach MetaData Xmit ExcelspreadsheetDefine Study Data Xmit SAS DatasetsWrite Study DefinitionMetadataxmitApply Study Definition CDISC approachCollect Patient Data MetaData Xmit ODM XML Data Xmit ODM XMLApply Patient DataDataxmit CDISC BenefitsWrite Patient Data More information exchange Increased automationAnalyze DataCopyright 2005, SAS Institute Inc. All rights reserved.7
ODM & Audit TrailWhoWhyWhatWhenCopyright 2005, SAS Institute Inc. All rights reserved.8
SDS, SDTM and SEND – Submission Standards SDS: Submissions Data Standards Refers to the implementation of the model for clinicalsubmissions (e.g. SDS v3.1.1) SDTM: Study Data Tabulation Model Refers to the model that supports clinical andpreclinical submissions data SEND: Standard for Exchange of Nonclinical Data Defines domains and variables for submitting all datagenerated from animal toxicity studiesCopyright 2005, SAS Institute Inc. All rights reserved.9
SDS V3.1.1: CDISC Standard DomainModels Observation ClassesInterventionsEventsFindings(80% of itionVitalsSubjCharRelatesSupp QualSubst UseMedHistPhysExamQS, MBCopyright 2005, SAS Institute Inc. All rights reserved.Study ObservationsECGCP, DVCommentsStudy DesignSpecial PurposeTables10
SDTM Basic Concepts Utilizes standard variable names, metadata, and data structureEach domain has required, expected, and permitted variablesNo redundancy (other than identifying variables)SDS team has developed standards, containing specific metadatafor 20 domainsCopyright 2005, SAS Institute Inc. All rights reserved.11
SDTM 3 general observation classes Interventions Events FindingsSpecial domains Demographics Comments Relationship between records in multiple domains Supplemental qualifier domainsCopyright 2005, SAS Institute Inc. All rights reserved.12
Specifications For Organizing The udydata-v1.1.pdfCopyright 2005, SAS Institute Inc. All rights reserved.13
SDTM Benefits Increase in efficiency Data transfers Data reviews Creation of analysis filesFlexible Supplemental domains Can accommodate a mixture of raw and derivedCopyright 2005, SAS Institute Inc. All rights reserved.14
ADaM – Analysis Dataset ModelUses for Analysis Datasets: Provide clear communication of the scientific results to regulatoryreviewers Replicate or verify the sponsor’s analyses, results, and conclusions Test the validity and robustness of the sponsor’s analyses andassumptions (what if ) Audit the data for inconsistencies and errors Status: Analysis Dataset Models Completed Change from baseline Time to event Categorical analysis Working on Additional Dataset Models Linear model Safety Analysis Ensuring compatibility with SDS Version 3.1 (SDTM)Copyright 2005, SAS Institute Inc. All rights reserved.15
Lab – Clinical Laboratory Data Model Core model designed to handle “simple lab data”: one test, one resultstructure 10 levels of content includes support of administrative information fortransfer of samples, reporting of results Production Version 1.0.1 - on CDISC web site Specification, data fields, reference ranges Includes Microbiology extensionCurrently standard approaches are included for Bar delimited ASCII (default representation) SAS XML HL7 RIM message More complex tests - handled by extensions Work on pharmacogenomics beginningCopyright 2005, SAS Institute Inc. All rights reserved.16
Case Report Tabulation Data DefinitionSpecification (CRTDDS aka define.xml) Machine readable replacement for define.pdf currently usedin submission process Organizes and describes submission content Extends ODM metadata for submission content Enhances general column descriptive information Adds item-level metadata support Supports linkage to external folders and filesCopyright 2005, SAS Institute Inc. All rights reserved.17
Protocol Representation Standard Initiated as an HL7 project to develop standardrepresentation of clinical trial protocol elements CDISC team formed to provide domain expertise Spreadsheet of elements, with glossary definitions open forpublic review and comment Initial Clinical Document Architecture (CDA) modeldeveloped and balloted through HL7Copyright 2005, SAS Institute Inc. All rights reserved.18
CDISC Biomedical Research IntegrationDomain Group (BRIDG) Follows the HL7 Development Framework Initiated in January 2004 by CDISC Board Developed through numerous modeling sessions withdomain experts and reviewed by CDISC, industry, FDA,NCI/NIH groups; led by HL7 RIM expert Purposes and Anticipated Benefits: To help ensure harmonization among CDISC models(present and future) To provide the industry with a standard model torepresent the clinical research domain To enable an HL7 implementation of the CDISC ODM To help harmonize the CDISC and HL7 standards To help enable interoperability between clinical researchand healthcare systemsCopyright 2005, SAS Institute Inc. All rights reserved.19
Evolution of CDISC Standards:Started with the end in mind ProtocolData SourcesOperational SubmissionOperationalDataDatabaseData LaboratoriesInterchangeOneHarmonized StandardInterchange Contract& Archive: Study Data& Archive:ResearchSDS, ADaM Audit TrailODM, LABOrganizationsSEND Metadata DevelopmentPartners Site CRFsSubmissionData CRT/DomainDatasets AnalysisDatasets MetadataODM Operational Data Model/StdSDS Submission Domain StandardsLAB Laboratory Data Model/StdADaM Analysis Data ModelsSEND Standards for the Exchange of Non-Clinical DataCopyright 2005, SAS Institute Inc. All rights reserved.20
How SAS Supports CDISCCopyright 2005, SAS Institute Inc. All rights reserved.
“At first glance, SAS might appear to be the loser in any standardsshift. After all, it owns the format in which clinical data areanalyzed . But [SAS] declares: Standards do not scare us. We embrace them. The company is both acutely sensitive to its large user base andattuned to the shifting winds of industry, where the Clinical DataInterchange Standards Consortium (CDISC) has been gainingtraction.”- Mark Uehling, Senior Science Editor, Bio-IT World eCliniquaThursday, Dec 9, 2004Copyright 2005, SAS Institute Inc. All rights reserved.22
Support for the CDISC Organization SAS is a corporate sponsor Ed Helton, of SAS, recently elected Chairman of the Boardfor CDISC Dave Handelsman is SAS’ representative on the IndustryAdvisory Board SAS has hosted the Industry Advisory Board meeting in thepast, and periodically hosts Board of Directors’ meetings SAS participates in several of the modelling teamsCopyright 2005, SAS Institute Inc. All rights reserved.23
SAS Software Developed for CDISC PROC CDISC ODM (v1.2.1): Data conversion between SAS and XML SDTM (v3.1): Data structure verification XML Engine ODM Native mode (v1.2.1)XML Engine and XMLMap ExtensionsNew base SAS formats/informats for ISO-8601SAS CDISC Viewer (ODM 1.2.1)See Tony Friebel’s talk at 16:05 today for more details: SASDataset Content Conversion to CDISC Data StandardsCopyright 2005, SAS Institute Inc. All rights reserved.24
PROC CDISC Examplelibname results 'SASEnvironment\SASCode\CDISC Demo\data' ;FILENAME XMLINP '\CDISC Demo\xml\ae.xml';PROC CDISCMODEL ODMformatActive YESREAD XMLINPformatNoReplace NO;ODMODMVersion "1.2"ODMminimumKeyset NO;CLINICALDATAOUT results.AESASDATASETNAME "AE" ;RUN;Copyright 2005, SAS Institute Inc. All rights reserved.25
SAS Integration Based on CDISC ODM ODM v1.2.1 used to bridge DataTrak EDC with SAS DrugDevelopment Incremental data is transferred from EDC server to SAS DrugDevelopment Scheduled, or Ad hoc Data is then: Extracted from XML (ODM) into normalized SAS data sets Compared to master files Updated according to ODM transaction types Once loaded, data sets are: Versioned Audit trailed Available for further transformation and analysisCopyright 2005, SAS Institute Inc. All rights reserved.26
SAS ETL StudioCopyright 2005, SAS Institute Inc. All rights reserved.27
ETL Studio Source Designer Target Designer Process DesignerCopyright 2005, SAS Institute Inc. All rights reserved.28
ETL StudioDesktop Customizable Trees Many Object types Document Source Table Target Table Job External Files Groups Libraries NotesetcCopyright 2005, SAS Institute Inc. All rights reserved.29
Source DesignerCopyright 2005, SAS Institute Inc. All rights reserved.30
Target DesignerCopyright 2005, SAS Institute Inc. All rights reserved.31
Process DesignerCopyright 2005, SAS Institute Inc. All rights reserved.32
Process DesignerCopyright 2005, SAS Institute Inc. All rights reserved.33
Code GeneratorSDDSchedulerCopyright 2005, SAS Institute Inc. All rights reserved.34
CDISC SDTM Data Model Implemented in the metadataImplements all currently defined modelsContains table definitions and model metadataFacilitates a workflow to define new modelsProvides supplemental tables for validation stepsCopyright 2005, SAS Institute Inc. All rights reserved.35
Standard DomainsCopyright 2005, SAS Institute Inc. All rights reserved.36
Reference Tables (controlled terminology)Copyright 2005, SAS Institute Inc. All rights reserved.37
SAS and SDTM as the Emerging StandardOCTAGON RESEARCH SOLUTIONS IDENTIFIED AS APRIMARY TRAINER FOR CLINICAL DATAINTERCHANGE STANDARDS CONSORTIUM (CDISC)Corporate Sponsor to Provide Training Curriculum onEmerging Data StandardsApril 4, 2005OCTAGON RESEARCH SOLUTIONS IMPLEMENTS SASTECHNOLOGY [SAS Enterprise ETL Server] TOREVOLUTIONIZE CDISC SDTM LEGACY CONVERSIONOFFERINGSApril 11, 2005Copyright 2005, SAS Institute Inc. All rights reserved.38
On the SAS Radar . define.xml Lab, SEND, ADaM Other emerging standardsCopyright 2005, SAS Institute Inc. All rights reserved.39
The Move to Standards “Faced with rapid changes, the nation’s healthcare system hasfallen short of its ability to translate information intoknowledge that can be used in practice, and to apply newtechnology safely and appropriately.The results are exactly what you would expect. Everyone whouses the current system constantly confronts largeinformation gaps, whether it’s at the doctor’s office, on thehospital ward or at government agencies charged withprotecting the public health. That goes for the FDA -- we’reno exception.”Dr. Mark McClellan, former FDA CommissionerCDISC Interchange, October 2003“Innovation depends upon standardization.”Dr. Bob O’Neill, Director, Office of Biostatistics, CDER, FDACopyright 2005, SAS Institute Inc. All rights reserved.40
Benefits of Standards – Regulatory View“The importance of a standard for the exchange of clinical trialdata cannot be overstated. FDA reviewers spend far toomuch valuable time simply reorganizing large amounts of datasubmitted in varying formats. Having the data presented in astandard structure will improve FDA’s ability to evaluate thedata and help speed new discoveries to the public.” -LesterCrawford, Former Commissioner, FDACopyright 2005, SAS Institute Inc. All rights reserved.41
“ But [SAS] declares: Standards do notscare us. We embrace them.”- Mark Uehling, Senior Science Editor, Bio-IT World eCliniquaThursday, Dec 9, 2004Copyright 2005, SAS Institute Inc. All rights reserved.42
Copyright 2005,2003, SAS Institute Inc. All rights reserved.43
NCI/NIH groups; led by HL7 RIM expert Purposes and Anticipated Benefits: To help ensure harmonization among CDISC models (present and future) To provide the industry with a standard model to represent the clinical research domain To enable an HL7 implementation of the CDISC ODM To help harmonize the CDISC and HL7 standards
CDISC 360 Implementation 3. Access and Membership Levels 4. New Environments 5. Private CDISC Library Instances . Implementation Guide Text CRFCollection Diff Content Between Versions CDISC 360 Informative Content. . ADaM Programming specification ADaM Metadata Mapping Metadata SDTM Metadata Analysis .
CDISC Define-XML Team Notes to Readers This is the specification for Version 2.0 of the CDISC Define -XML standard. This is an update of the Case Report Tabulation Data Definition Version 1. 0.0 Specification. Revision History Date Version Summary of Changes 2005-02-05 1.0.0 This is the official implementation version of the Case Report
(CTAUG/CDISC Therapeutic Area User Guide) available in the CDISC Standard Controlled Terminology; its use is also recommended by the FDA Study Data Technical Conformance Guide (October 2018 on) THE STATE OF THE ART The first TAUG was released in 2011 (Alzheimer) and at the end of 2018 overall 30 TAUGs were
CDISC 360 Enriched ARM Metadata R Shiny Select TFL of Interest Review data Customize TFL Layout & Metadata Select TFL Layout (Template) SAS Generate SAS Program and Define.xml
David Handelsman CDISC Industry Advisory Board .
Jul 23, 2015 · Review Status Summary Internal Review Concluded June 11. th Team received and responded to 40 comments CDISC SRC Review Received and addressed 100 comments Approval to post for public review on July 21 Public Review Happening now! Anyone welcome to review and comment Comment period closes . 08/24/2015. 7
The Clinical Data Interchange Standards Consortium (CDISC) is an open, multidisciplinary neutral . ports the study plan and the submission of elements of the plan to enable evaluation of the actual data in accordance with the plan. The BRIDG model for . unique file formats a clinical application needs to support. ODM also has a number of .
Adolf Hitler Translated into English by James Murphy . Author's Introduction ON APRIL 1st, 1924, I began to serve my sentence of detention in the Fortress of Landsberg am Lech, following the verdict of the Munich People's Court of that time. After years of uninterrupted labour it was now possible for the first time to begin a work which many had asked for and which I myself felt would be .
