© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 1 Initial Investment in CDISC Data Standards in Clinical Organisations © 2010 Octagon Research Solutions, Inc. All Rights Reserved. Ken Stoltzfus Octagon Research Solutions PhUSE 2010 Berlin Knitting fog, herding cats, and other challenging endeavours

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 2 About Octagon Octagon Research Solutions –A development partnering organization that offers regulatory, clinical, process and IT solutions to the life sciences industry. Octagon experience on topic : –600 studies converted to SDTM & ADaM (8,000+ domains) –Current CDISC SDS team lead –2 of 6 co-authors of CDISC SDTM –Current CDISC team membership: SDS, ADaM, Trial Design, Controlled Terminology, and XML –CDISC-authorized SDTM trainers

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 3 Agenda Background Standards Governance People Standards Processes Technical Solutions

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 4 Background

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 5 5 Standards Who needs them ????

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 6 6 Standards Success story !!!!

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 7 7 Value Example: Analysis and Submission –Integrated standards provide traceability when the regulatory reviewer has questions –Data mining for safety signals facilitated by adherence to a common standard structure –Emerging regulatory standards yield reviews with decreased review time and increased data accuracy

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 8 8 Metrics Clinical Study Activities Current Industry Average (months) After CDISC Standards Implementation (months) Time Savings (months) Cost Savings (USD Million) Study Start-up Study Conduct Analysis & Reporting Cumulative Impact of CDISC Standards Implementation on Clinical Study Cycle Time & Cost 1 1 “Business Case for CDISC Standards: Full Report, PhRMA-Gartner-CDISC Project” (May 2007),

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 9 9 Obstacles Acknowledging the fears –Inhibiting scientific innovation –Perception of standards governance as bureaucracy –Business needs compete with standards needs –Unacceptable cost in time and resources –The standards will not be stable

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 10 Standards Governance

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 11 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 11 Standards Governance What exactly is standards governance? –Oversight –Decision-making –Development –Maintenance –Compliance –Enforcement Solution: Standards Governance Framework

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 12 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 12 Standards Governance Standards – Governance = No standards at all –Irregular, non-compliant usage –Eventually non-existent Minimum framework: –Roles & responsibilities –Development resources –Business guidelines Maximum framework: –Processes –Tools Standards Governance Framework

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 13 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 13 Standards Governance Standards People Processes Technical Solutions Leadership Content decision-makers Developers Data stewards Internal standards CDISC standards InterpretationDevelopment Business Guidelines Maintenance SOPs Request system CDR MDR

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 14 People

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 15 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 15 People Numbers –Varies from company to company –Part-time resources far outnumber the full-time ones Full-time –Team leader(s) –Decision-makers (content & structure) Part-time –Oncology physician for RECIST tumor measurements –EDC screen developer including monitoring needs in eCRF –Statistical programmer writing standard macro code –IT rep as liaison - governance group to IT project managers

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 16 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 16 People Content decision-makers –Subject matter experts (medical, clinical, statistical) Developers –Technical expertise –Operational managers Administrators –Tracking requests –Updating metadata –Uploading the latest version Data Stewards –TAs –Functional areas Don’t forget the IT function!

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 17 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 17 People High-level directive that creates buy-in –Improved data quality –Improved data transparency –Accurate, consistent submissions –Speed of study execution –Maximization of study execution resources –Cost savings –Compliance with anticipated regulatory requirements –Keeping up with competitors who are becoming more streamlined

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 18 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 18 People Definition of standards drivers –Bridge gap between the strategic & operational –Working knowledge of standards (doesn’t have to be a standards expert) –A champion for standards in their functional area

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 19 Standards

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 20 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 20 Standards What are Standards ???? –A company’s methodology in a stable format –Intellectual property in some cases –Internal vs external –Reusable pieces used in clinical trials Data definition files eCRF screens EDC data extracts Data checking utilities/programs Macros for standard results Analysis dataset programs XML transfer files

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 21 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 21 Standards 80 / 20 rule 20: Only 20% of total content that a function delivers for a study should come from customized or newly developed standards 80: Of the total content that a function delivers for a study, 80% should come from quick, efficient, reusable standards Custom Reusable

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 22 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 22 Standards Levels to facilitate management of standards –Global –Therapeutic Areas –Project Custom Reusable

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 23 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 23 Standards SDTM implementation considerations –SDTM Findings class in collection: horizontal vs vertical –SDTM mapping: stability of standard CRFs –Best location in the data lifecycle for conversion to SDTM –SDTM experience in the EDC functional area –Linear implementation: CDASH to SDTM to ADaM –Which databases house data needed to build Trial Design? –SDTM & ADaM metadata –Define.xml: How? Who? –SDTM training: Who? What? When?

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 24 Processes

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 25 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 25 Processes Governance charter –Strategic –Structure –Organisation –Roles & Responsibilities –Scope

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 26 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 26 Processes Standard Operating Procedures (SOPs) –Development of standards –Maintenance of standards –Request process for new or revised standards –Role of the data steward in governance –Access control for standards storage –Waiver process

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 27 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 27 Processes Business Guidelines for CDISC Standards –Mapping decisions –Common practices –Interpretation

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 28 Technical Solutions

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 29 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 29 Technical Solutions Do they really help ??? Technical solutions that make a difference –Standards request system –Clinical data repository (CDR) –Metadata repository (MDR)

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 30 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 30 Technical Solutions Standards Request System –The face of the standards governance framework –Allow study teams to submit standards requests –Allow for supportive files –Assign unique identification number –Track requests by date, resolution, user, etc. –Fulfill request with discussions, questions, and decisions –Provide users with status of their requests –Provide reporting capabilities (metrics, etc.)

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 31 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 31 Technical Solutions Clinical Data Repository –Repose all data in standard centralized location –Import, storage, and export of data in SDTM –Validated inbound ETL process –Promote standardized, validated data import and export –Support the production of analysis datasets and clinical study reports –Interoperability with clinical systems across the clinical data architecture

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 32 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 32 Technical Solutions Metadata Repository –Repose all metadata in standard centralized location –Repose study definition metadata –Ensure areas for all standards (global, TA, project) –Import and export standards metadata –Interoperability with clinical systems across the clinical data architecture –Generate governance process workflows –Maintain proper version control, data traceability & audit trails

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 33 Summary

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 34 Standards Governance –People –Standards –Processes –Technical Solutions

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 35 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 35 Spend time thinking up-front

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 36 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 36 Avoid herding cats

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 37 © 2010 Octagon Research Solutions, Inc. All Rights Reserved. 37 Acknowledgements Barry Cohen Dave Evans Tore Haglund Stephen Harrison Harpreet Sahni

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 38 Contact Information Ken Stoltzfus Clinical Data Strategies Octagon Research Solutions 585 East Swedesford Road, Suite 200 Wayne, PA USA Tel: (Ext. 5891)

© 2010 Octagon Research Solutions, Inc. All Rights Reserved. 39 Questions ?