Beyond regulatory submission - Standards Metadata Management Kevin Lee CDISC NJ Meeting at 06/17/2015 We help our Clients deliver better outcomes, so they can improve the quality of people’s lives.

Agenda Regulatory Requirement on Clinical Data Standards(i.e., CDISC) Standards driven process Standards Metadata Management Final Thoughts © 2015 Accenture All Rights Reserved.

Standards? What do we think first about Standards? © 2015 Accenture All Rights Reserved.

Standards driven electronic submission of clinical trial data © 2015 Accenture All Rights Reserved.

Current Status in eSubmission in CDER FDA First, let’s us take a look at current status in electronic submission. © 2014 Accenture All Rights Reserved.

Current Status in CDISC Submission in CDER FDA In 2010, 23% of SDTM in NDA In 2011, 39% of SDTM and 32% in ADaM in NDA In 2013, 55% of SDTM in NDA And, if we look at CDISC submission, FDA is also getting more of CDISC data. © 2014 Accenture All Rights Reserved.

Section 745A(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) Enhanced by Food and Drug Administration Safety and Innovation Act (FDASIA) on July 9, 2012. Requires that submissions be submitted in electronic format. © 2014 Accenture All Rights Reserved.

New FDA Guidance on CDISC eSubmission Guidance for Industry: Providing Regulatory Submissions in Electronic Format – Submissions Under Section 745A (a) of the Federal Food Drug, and Cosmetic Act Guidance for Industry: Providing Regulatory Submissions in Electronic Format – Standardized Study Data Binding rather than recommendation The FDA Guidance document, once finalized, will be binding rather than recommendation. © 2014 Accenture All Rights Reserved.

What else for Standards? Anything else beside submission? What else can we do with standards? © 2015 Accenture All Rights Reserved.

Accenture Survey on Standards usage in the future © 2014 Accenture All Rights Reserved.

What is beyond standards? Standards driven process © 2015 Accenture All Rights Reserved.

Henry Ford Assembly Line The Model T was Ford's first automobile mass produced on moving assembly lines with completely interchangeable STANDARDized parts. (Dec 1st, 1913) © 2015 Accenture All Rights Reserved.

Model T production and price over year 1910: $900 and 20,000 vs 1925: $260 and 2,000,000 © 2015 Accenture All Rights Reserved.

Thoughts: Can we build an automated process with Standards just like Henry Ford did? © 2015 Accenture All Rights Reserved.

How to apply Standards to clinical artefacts development Henry Ford Car production Model T Interchangeable Standardized parts Automated Assembly line Clinical artefacts development SDTM datasets SDTM & CDASH(EDC), CT standards Automated ETL system © 2015 Accenture All Rights Reserved.

Standards driven automated clinical artefacts development CDASH(EDC) SDTM ETL system Clinical Artefacts CDASH(EDC) datasets SDTM datasets © 2015 Accenture All Rights Reserved.

Questions What are needed for automated clinical artefacts development? © 2015 Accenture All Rights Reserved.

Things needed for automated clinical artefacts development Standards metadata – source and target datasets ETL system System readable transformation metadata Standards Metadata Management © 2015 Accenture All Rights Reserved.

Types of Standards Metadata Structural source metadata Dataset Variable Name Variable Label Type CT DEMO USUBJID Unique Subject Identifier Char Structural target metadata Dataset Variable Name Variable Label Type CT Role DM USUBJID Unique Subject Identifier Char Identifier Age Num System readable transformation metadata Target dataset Target variable Machine readable derivation Source dataset Source variable DM USUBJID = DEMO AGE %AGE(DM.RFSTDTC – BRTHDTC) © 2015 Accenture All Rights Reserved.

Questions What if Standards change or evolve? © 2015 Accenture All Rights Reserved.

Standards Metadata Management Definition Managing data about standards data Examples of metadata Variable Name Variable Label Type CT Role Core STUDYID Study Identifier Char Identifier Req DOMAIN Domain Abbreviation DM USUBJID Unique Subject Identifier © 2015 Accenture All Rights Reserved.

Examples of Metadata Management Creating new standards (e.g., variables and domains) Modifying the attributes (e.g., label, type) of current standards Adding the new attributes to current standards Archiving the standards Managing the information that transforms data into a new structure (e.g.: CDASH to SDTM) Leveraging the Schedule of Events table to determine the data domains required for a study Assigning versions (e.g., major or minor) to standards after changes Maintaining multiple versions of standards (e.g., SDTMIG 3.1.2, 3.1.3) © 2015 Accenture All Rights Reserved.

Evolution of Standards Metadata Management Initial No Standards Metadata Management Basic Siloed, manual management of spreadsheet-based Standards metadata Advanced Introduction of Centralized MDR and Development of Standard Metadata using MDR Optimizing Study Definitions Standards Metadata within the MDR for automating metadata-driven processing Innovative Protocol-driven Study Definitions automatically generated from Trial-Level Standards Metadata enabled by semantic metadata So, let’s look at partnerships in Pharmaceutical industry. In 2012 Avoca Report, 50% of Drug companies are using partnerships and about 70% of CRO are using partnerships. © 2014 Accenture All Rights Reserved.

Evolution of metadata system Spreadsheet or document Database Metadata Repository © 2015 Accenture All Rights Reserved.

Metadata Repository (MDR) Definition Database created to store metadata Function Storages of Standards metadata in global library Manage Standards metadata Govern Standards metadata Develop study-level metadata from global library Feed metadata to other system(e.g., EDC and ETL system) © 2015 Accenture All Rights Reserved.

Study level metadata definition development in MDR Global Library Study 001 Protocol Protocol CDASH CDASH SDTM SDTM ADaM ADaM TFL TFL © 2015 Accenture All Rights Reserved.

Why is Study Level metadata definition in MDR important? It can dictate study level artefacts development. Study 001 Study 001 Protocol Protocol EDC database CDASH eCRF SDTM SDTM datasets ADaM ADaM datasets TFL TFL © 2015 Accenture All Rights Reserved.

Management Final Thought Standards Metadata Standards Regulatory Clinical Data Submission Standards Metadata-driven Automated Clinical Artefacts Development © 2015 Accenture All Rights Reserved.

Contacts and Questions Kevin Lee Email: kevin.s.lee@accenture.com LinkedIn: www.linkedin.com/in/HelloKev inLee Slides: www.slideshare.net/KevinLee 56 Tweet: @HelloKevinLee Blogs: HiKevinLee.tumblr.com © 2015 Accenture All Rights Reserved.