emerging data file initiatives & standards: potential impact on global clinical studies

Emerging Data File Emerging Data File Initiatives & Initiatives & Standards: Standards: Potential Impact on Potential Impact on Global Clinical Global Clinical StudiesStudies

Co-PresentersCo-Presenters

Ginger ClasbyGinger ClasbyExecutive VPExecutive VP

Business DevelopmentBusiness Development

gclasby@[email protected]

Don HurstDon HurstDirectorDirector

Clinical Information Clinical Information TechnologyTechnology

dhurst@[email protected]

Corporate Goal Corporate Goal Optimize revenue stream by Optimize revenue stream by getting products to market as getting products to market as

quickly as possiblequickly as possible

Accomplishing the Goal Accomplishing the Goal

Enroll subjects as quickly as Enroll subjects as quickly as possiblepossible

• Sites in US & OUSSites in US & OUS

• Experienced sitesExperienced sites

• Sophisticated px recruitment Sophisticated px recruitment programsprograms


Maximize clinical trial operationalMaximize clinical trial operationalefficiencies to minimize time from lastefficiencies to minimize time from last

data in to database lockdata in to database lock• StandardizationStandardization

• Internet applications for study management Internet applications for study management docsdocs

• Electronic Data Capture (EDC)Electronic Data Capture (EDC)

• Detailed monitoring of subject exam schedulesDetailed monitoring of subject exam schedules


Minimize time for statistical analysis &Minimize time for statistical analysis &CSR developmentCSR development

• StandardizationStandardization

• eXtensible Markup Language (XML)eXtensible Markup Language (XML)

• Develop/validate templates prior to Develop/validate templates prior to database lockdatabase lock


Minimize regulatory agency Minimize regulatory agency reviewreview

periodperiod

• StandardizationStandardization

• Electronic submissionsElectronic submissions

• XMLXML

Oops!Oops!Differing data capture & Differing data capture &

reporting formatsreporting formats

across countries/regionsacross countries/regions

Differing Formats Differing Formats • Data conventions: Data conventions: mo/day/yr or mo/day/yr or

day/mo/yr?day/mo/yr?

• Measurement units: Measurement units: kg or lb?kg or lb?

• Variable names: Variable names: English, French, English, French, German or ?German or ?

• Report content/structure varies Report content/structure varies widely by country or regionwidely by country or region

CDISCCDISC

Clinical Data Clinical Data Interchange Interchange Standards Standards

ConsortiumConsortium

CDISC BackgroundCDISC Background • Established 1997Established 1997

• Assumes use of EDCAssumes use of EDC

• Collaboration to produce functional Collaboration to produce functional standard data models facilitating data standard data models facilitating data interchange between industry stakeholders interchange between industry stakeholders

• Supports end-to-end data flow within trials, Supports end-to-end data flow within trials, from source document to regulatory from source document to regulatory submissionsubmission

CDISC “Deliverables”CDISC “Deliverables” Operational Data Modeling (ODM)Operational Data Modeling (ODM)

Data acquisition Data acquisition Data Data archivingarchiving

Submission Data Modeling (SDM)Submission Data Modeling (SDM)

Operating database Reg Operating database Reg submissionsubmission

CDISC “Reach”CDISC “Reach”• Biopharmaceutical study focusBiopharmaceutical study focus

• Active collaboration with FDAActive collaboration with FDA

• Active collaboration with Active collaboration with analogous regulatory analogous regulatory organizations in Europe & Japanorganizations in Europe & Japan

CDISC vs. ICHCDISC vs. ICH • ICH – working toward global ICH – working toward global

submission standardssubmission standards

• CDISC – working on CDISC – working on standardization of submissions at standardization of submissions at the data levelthe data level

CDISC vs. HL7CDISC vs. HL7 • HL7 – data standards for all health HL7 – data standards for all health

care operations, including care operations, including reimbursement & order processing – reimbursement & order processing – no clinical trials focusno clinical trials focus

• CDISC – oriented to CDISC – oriented to biopharmaceutical product biopharmaceutical product development onlydevelopment only

1.1. EDC: environment manipulating the filesEDC: environment manipulating the filesA.A. Hardware characteristicsHardware characteristicsB.B. Software & database/file characteristicsSoftware & database/file characteristics

2.2. XML: a vendor neutral file standard XML: a vendor neutral file standard A.A. Brief historyBrief historyB.B. SGMLSGMLC.C. HTMLHTMLD.D. XMLXML

3.3. CDISC CDISC A.A. ODM – Operational Data ModelODM – Operational Data ModelB.B. SDM - Submissions Data ModelSDM - Submissions Data Model

Three Technological Trends Impacting Three Technological Trends Impacting Clinical Study and Data Management Clinical Study and Data Management

Design for Global TrialsDesign for Global Trials

Electronic Data CaptureElectronic Data Capture

Hardware Characteristics:Hardware Characteristics:

1.1. Web enabled, wired or wirelessWeb enabled, wired or wireless

2.2. Transfer devicesTransfer devicesA.A. PDA (Palm Pilot) for patient diaries, PDA (Palm Pilot) for patient diaries,

etc.etc.B.B. Blackberry devices (Raspberry Blackberry devices (Raspberry

devices??)devices??)C.C. IVRS (Interactive Voice Response IVRS (Interactive Voice Response

Systems)Systems)D.D. Scanning (CRFs)Scanning (CRFs)E.E. KeyboardKeyboardF.F. Smart phonesSmart phones


Hardware Characteristics:Hardware Characteristics:

3.3. ServersServersA.A. Many different types of servers Many different types of servers

(authentication, mail, database, (authentication, mail, database, backup, Citrix, etc.)backup, Citrix, etc.)

B.B. Server to server communicationServer to server communicationC.C. Device to server communicationDevice to server communication

4.4. Communication protocolsCommunication protocolsA.A. TCP/IPTCP/IPB.B. FTPFTPC.C. BisynchronousBisynchronousD.D. AsynchronousAsynchronous


Software & Database/File Software & Database/File Characteristics:Characteristics:

1.1. Operating systemsOperating systemsA.A. LinuxLinuxB.B. Windows 2000Windows 2000C.C. SolarisSolaris

2.2. Front end (Graphical User Front end (Graphical User Interface)Interface)A.A. HTML HTML B.B. JAVAJAVAC.C. C+ and other languagesC+ and other languages



3.3. Backend databaseBackend databaseA.A. Flat Flat B.B. SQL/Server (Relational)SQL/Server (Relational)C.C. UDB/DB2 (Relational)UDB/DB2 (Relational)D.D. XML (hierarchical)XML (hierarchical)

4.4. Client/server typeClient/server typeA.A. Thin (Explorer based only)Thin (Explorer based only)B.B. Hybrid (Explorer + some client Hybrid (Explorer + some client

download)download)C.C. Thick (Major client download…Thick (Major client download…

usually for offline followed by usually for offline followed by scheduled uploads)scheduled uploads)



5.5. Types of files used between devicesTypes of files used between devicesA.A. Only one type of file: flat and Only one type of file: flat and

sequentialsequentialB.B. Characteristics of flat file are Characteristics of flat file are

dependent on what is encoded from dependent on what is encoded from the source and how file is the source and how file is interpreted, or reconstructed, by the interpreted, or reconstructed, by the target. Or another way of saying it, target. Or another way of saying it, is what association is with the file is what association is with the file (icon).(icon).

C.C. A flat file can be many different A flat file can be many different types:types:1)1) SAS transport, Excel, Word, SAS transport, Excel, Word,

unloaded relational, zipped, unloaded relational, zipped, Adobe PDF, etc.Adobe PDF, etc.

2)2) XML fileXML file

XMXMLL

1.1. What is it?What is it?A.A. eeXXtensible Markup Languagetensible Markup LanguageB.B. Non-proprietary, platform-independent Non-proprietary, platform-independent

meta-language for hierarchically meta-language for hierarchically structuring informationstructuring information

2.2. What is XML’s history?What is XML’s history?A.A. Subset of the International Standards Subset of the International Standards

Organization (ISO) Standard Generalized Organization (ISO) Standard Generalized Markup Language (SGML), ISO 8879:1986 Markup Language (SGML), ISO 8879:1986

B.B. SGML is an ISO Standard - ISO 8879:1986 SGML is an ISO Standard - ISO 8879:1986 C.C. SGML Established Standard for 12 years. SGML Established Standard for 12 years. D.D. SGML released as ISO8879 in 1986 SGML released as ISO8879 in 1986 E.E. At SGML 96 Conference in Boston, XML At SGML 96 Conference in Boston, XML

released by a working group associated released by a working group associated with the W3C. with the W3C.

F.F. SGML ## was previous name for XML SGML ## was previous name for XML #### ####

G.G. XML 1.0 is W3C recommendation (32 XML 1.0 is W3C recommendation (32 pages) pages)

H.H. XML became recommendation in February, XML became recommendation in February, 19981998

XMXMLL

3.3. Where is it used?Where is it used?A.A. Almost all industry groupsAlmost all industry groupsB.B. Heavily used in the banking sectorHeavily used in the banking sector

4.4. How is XML related to SGML and HTML?How is XML related to SGML and HTML?A.A. XML + HTML = SGML XML + HTML = SGML B.B. SGML – Standard Generalized Markup SGML – Standard Generalized Markup

LanguageLanguage1)1) Context (HTML)Context (HTML)2)2) Content (XML)Content (XML)

C.C. HTML - HyperText Markup LanguageHTML - HyperText Markup Language 1)1) Used in Web pagesUsed in Web pages2)2) Can emphasize text, graphics, links, Can emphasize text, graphics, links,

etc.etc.D.D. XML XML

1)1) Hierarchical in organizationHierarchical in organization2)2) Uses data tags to classify dataUses data tags to classify data

XMXMLL

5. What does XML look like (normal view not 5. What does XML look like (normal view not indented)? indented)?

XMXMLL

6.6. Things to remember about XMLThings to remember about XML

A.A. Already an international standardAlready an international standard

B.B. An ISO standardAn ISO standard

C.C. Standard for the electronic Standard for the electronic exchange of information in most exchange of information in most industry groupsindustry groups

D.D. Although a flat and sequential file, it Although a flat and sequential file, it has structurehas structure

E.E. ““Content” based, while HTML is Content” based, while HTML is “context” based“context” based

CDISCCDISC

1.1. CClinical linical DData ata IInterchange nterchange SStandards tandards CConsortiumonsortium

2.2. Developing a common interchange Developing a common interchange standard for clinical datastandard for clinical data

3.3. Accomplish through the development Accomplish through the development of meta-data modelsof meta-data models

CDISCCDISC4.4. Benefits of standard meta-data models:Benefits of standard meta-data models:

A.A. Clin. labs do not have to support Clin. labs do not have to support different formatsdifferent formats

B.B. CROs no longer have to develop CROs no longer have to develop completely new databases to meet completely new databases to meet unique specifications of each trialunique specifications of each trial

C.C. EDC providers do not need to EDC providers do not need to customize exchange format for each customize exchange format for each new clientnew client

D.D. Sponsors can receive data in standard Sponsors can receive data in standard format in less timeformat in less time

E.E. Regulatory reviewers can more quickly Regulatory reviewers can more quickly and easily review submission dataand easily review submission data

CDISCDISCC

CDISCCDISC5.5. Current Meta-Data modelsCurrent Meta-Data models

A.A. ODM – Operational Data ModelODM – Operational Data Model

B.B. SDM - Submissions Data SDM - Submissions Data ModelModel

C.C. RIM - Reference Information RIM - Reference Information ModelModel

D.D. ADaM – Analysis Dataset ModelADaM – Analysis Dataset Model

E.E. LAB – Laboratory Standards LAB – Laboratory Standards (LOINS(LOINS))

CDISCCDISC6.6. ODM – Operational Data Model GoalsODM – Operational Data Model Goals

A.A. Develop vendor independent Develop vendor independent models for interchange and models for interchange and archive of clinical data using archive of clinical data using metadatametadata

B.B. Base models on XML technologyBase models on XML technology

CDISCCDISC7.7. ODM – Overview StructureODM – Overview Structure

CDISCCDISC8.8. SDM – Submissions Data Model SDM – Submissions Data Model

(Domains)(Domains)• DemographicsDemographics

• DispositionDisposition

• ExposureExposure

• Labs (Chemistry, Labs (Chemistry, Hematology, Urinalysis)Hematology, Urinalysis)

• Physical ExamPhysical Exam

• Medical HistoryMedical History

• Concomitant Concomitant MedicationsMedications

• Adverse EventsAdverse Events

• Vitals (Horizontal)Vitals (Horizontal)

• Vitals (Vertical)Vitals (Vertical)

• ECG (Horizontal)ECG (Horizontal)

• EKG (Vertical)EKG (Vertical)

CDISCCDISC9.9. Other data models receiving top Other data models receiving top

prioritypriority

A.A. PharmacogenomicsPharmacogenomics

B.B. MicrobiologyMicrobiology

Summary (and peek into the Summary (and peek into the future)future)

1.1. Three trends are merging to bring a Three trends are merging to bring a drug/device to regulatory review in a drug/device to regulatory review in a faster, more standardized package.faster, more standardized package.

2.2. The merging of the trends will help The merging of the trends will help lower one of the major costs of trials lower one of the major costs of trials and remove one of the traditional and remove one of the traditional bottlenecks prior to submission.bottlenecks prior to submission.

3.3. The merging trends have gained such The merging trends have gained such momentum that the SAS Institute has momentum that the SAS Institute has invested and created a new procedure invested and created a new procedure called “PROC CDISC”.called “PROC CDISC”.

emerging data file initiatives & standards: potential impact on global clinical studies

Documents

data level slide

data levelcdisc

possible slide

regulatory submission

countriesregions slide

hl7 hl7 data standards

database lock slide

database reg submission