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

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Emerging Data File Initiatives Standards
Potential Impact on Global Clinical Studies

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Co-Presenters

• Ginger Clasby
• Executive VP
• Business Development
• gclasby_at_promedica-intl.com

• Don Hurst
• Director
• Clinical Information Technology
• dhurst_at_promedica-intl.com

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Corporate Goal

• Optimize revenue stream by getting products to
  market as quickly as possible

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Accomplishing the Goal

• Enroll subjects as quickly as possible
• Sites in US OUS
• Experienced sites
• Sophisticated px recruitment programs

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Accomplishing the Goal

• Maximize clinical trial operational
• efficiencies to minimize time from last
• data in to database lock
• Standardization
• Internet applications for study management docs
• Electronic Data Capture (EDC)
• Detailed monitoring of subject exam schedules

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Accomplishing the Goal

• Minimize time for statistical analysis
• CSR development
• Standardization
• eXtensible Markup Language (XML)
• Develop/validate templates prior to database lock

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Accomplishing the Goal

• Minimize regulatory agency review
• period
• Standardization
• Electronic submissions
• XML

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Oops!

• Differing data capture reporting formats
• across countries/regions

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Differing Formats

• Data conventions mo/day/yr or day/mo/yr?
• Measurement units kg or lb?
• Variable names English, French, German or ?
• Report content/structure varies widely by country
  or region

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CDISC

• Clinical Data Interchange Standards Consortium

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CDISC Background

• Established 1997
• Assumes use of EDC
• Collaboration to produce functional standard data
  models facilitating data interchange between
  industry stakeholders
• Supports end-to-end data flow within trials, from
  source document to regulatory submission

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CDISC Deliverables

• Operational Data Modeling (ODM)
• Data acquisition Data archiving
• Submission Data Modeling (SDM)
• Operating database Reg submission

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CDISC Reach

• Biopharmaceutical study focus
• Active collaboration with FDA
• Active collaboration with analogous regulatory
  organizations in Europe Japan

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CDISC vs. ICH

• ICH working toward global submission standards
• CDISC working on standardization of submissions
  at the data level

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CDISC vs. HL7

• HL7 data standards for all health care
  operations, including reimbursement order
  processing no clinical trials focus
• CDISC oriented to biopharmaceutical product
  development only

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Three Technological Trends Impacting Clinical
Study and Data Management Design for Global Trials

• EDC environment manipulating the files
• Hardware characteristics
• Software database/file characteristics
• XML a vendor neutral file standard
• Brief history
• SGML
• HTML
• XML
• CDISC
• ODM Operational Data Model
• SDM - Submissions Data Model

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Electronic Data Capture

• Hardware Characteristics
• Web enabled, wired or wireless
• Transfer devices
• PDA (Palm Pilot) for patient diaries, etc.
• Blackberry devices (Raspberry devices??)
• IVRS (Interactive Voice Response Systems)
• Scanning (CRFs)
• Keyboard
• Smart phones

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Electronic Data Capture

• Hardware Characteristics
• 3. Servers
• Many different types of servers (authentication,
  mail, database, backup, Citrix, etc.)
• Server to server communication
• Device to server communication
• Communication protocols
• TCP/IP
• FTP
• Bisynchronous
• Asynchronous

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Electronic Data Capture

• Software Database/File Characteristics
• Operating systems
• Linux
• Windows 2000
• Solaris
• Front end (Graphical User Interface)
• HTML
• JAVA
• C and other languages

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Electronic Data Capture

• Software Database/File Characteristics
• 3. Backend database
• Flat
• SQL/Server (Relational)
• UDB/DB2 (Relational)
• XML (hierarchical)
• 4. Client/server type
• Thin (Explorer based only)
• Hybrid (Explorer some client download)
• Thick (Major client downloadusually for offline
  followed by scheduled uploads)

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Electronic Data Capture

• Software Database/File Characteristics
• 5. Types of files used between devices
• Only one type of file flat and sequential
• Characteristics of flat file are dependent on
  what is encoded from the source and how file is
  interpreted, or reconstructed, by the target. Or
  another way of saying it, is what association is
  with the file (icon).
• A flat file can be many different types
• SAS transport, Excel, Word, unloaded relational,
  zipped, Adobe PDF, etc.
• XML file

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XML

• What is it?
• eXtensible Markup Language
• Non-proprietary, platform-independent
  meta-language for hierarchically structuring
  information
• What is XMLs history?
• Subset of the International Standards
  Organization (ISO) Standard Generalized Markup
  Language (SGML), ISO 88791986
• SGML is an ISO Standard - ISO 88791986
• SGML Established Standard for 12 years.
• SGML released as ISO8879 in 1986
• At SGML 96 Conference in Boston, XML released by
  a working group associated with the W3C.
• SGML was previous name for XML
• XML 1.0 is W3C recommendation (32 pages)
• XML became recommendation in February, 1998

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XML

• 3. Where is it used?
• Almost all industry groups
• Heavily used in the banking sector
• 4. How is XML related to SGML and HTML?
• XML HTML SGML
• SGML Standard Generalized Markup Language
• Context (HTML)
• Content (XML)
• HTML - HyperText Markup Language
• Used in Web pages
• Can emphasize text, graphics, links, etc.
• XML
• Hierarchical in organization
• Uses data tags to classify data

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

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XML

• 6. Things to remember about XML
• Already an international standard
• An ISO standard
• Standard for the electronic exchange of
  information in most industry groups
• Although a flat and sequential file, it has
  structure
• Content based, while HTML is context based

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CDISC

1. Clinical Data Interchange Standards Consortium
2. Developing a common interchange standard for
   clinical data
3. Accomplish through the development of meta-data
   models

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CDISC

• 4. Benefits of standard meta-data models
• Clin. labs do not have to support different
  formats
• CROs no longer have to develop completely new
  databases to meet unique specifications of each
  trial
• EDC providers do not need to customize exchange
  format for each new client
• Sponsors can receive data in standard format in
  less time
• Regulatory reviewers can more quickly and easily
  review submission data

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CDISC

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CDISC

• 5. Current Meta-Data models
• ODM Operational Data Model
• SDM - Submissions Data Model
• RIM - Reference Information Model
• ADaM Analysis Dataset Model
• LAB Laboratory Standards (LOINS)

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CDISC

• 6. ODM Operational Data Model Goals
• Develop vendor independent models for interchange
  and archive of clinical data using metadata
• Base models on XML technology

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CDISC
7. ODM Overview Structure

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CDISC
8. SDM Submissions Data Model (Domains)

• Demographics
• Disposition
• Exposure
• Labs (Chemistry, Hematology, Urinalysis)
• Physical Exam
• Medical History

• Concomitant Medications
• Adverse Events
• Vitals (Horizontal)
• Vitals (Vertical)
• ECG (Horizontal)
• EKG (Vertical)

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CDISC

• 9. Other data models receiving top priority
• Pharmacogenomics
• Microbiology

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Summary (and peek into the future)

1. Three trends are merging to bring a drug/device
   to regulatory review in a faster, more
   standardized package.
2. The merging of the trends will help lower one of
   the major costs of trials and remove one of the
   traditional bottlenecks prior to submission.
3. The merging trends have gained such momentum that
   the SAS Institute has invested and created a new
   procedure called PROC CDISC.