PhUSE Computational Science Symposium Working Groups An Experiment in Collaboration

What is PhUSE? Pharmaceutical Users Software Exchange Global group of programmers, statisticians, and data scientists Vendor neutral, Inclusive, and Open Mission: Provide platform for creating & sharing ideas, implementing tools & standards around data, and exploring innovative methods and technologies

Old Paradigm FDA Please tell us what to do

Paradigm Shift

CSS Timeline 2008: PhUSE and FDA collaborate on Wiki2009: FDA forms CSC2010/11: FDA hosts first two CSC meetings2012: First Annual CSS Meeting2013/14: Annual CSS Meetings

What CSS WGs Are? Work on best practices for standards and technology implementation Discuss and summarize challenges with implementation Implementation Try ideas using new technology e.g., semantic modeling, cloud- based implementation Test and provide feedback on new standards and processes Incubator Open forum for sharing ideas across FDA, Industry, and other organizations Provide platforms (wikis, code libraries) for sharing information Collaboration

What CSS WGs are Not Projects do not create, define and/or recommend policy or guideline changes FDA individuals provide input only Policy CDISC, HL7 and other SDOs create standards; CSS Working Groups tackle implementation and best practices around standards Standards Projects are not a place to ‘market’ technology Open collaboration in a non-competitive environment Commercial

Optimizing Use of Data Standards Emerging Technologies Standard Scripts for Reporting and Analysis Non-Clinical Roadmap and Implementation Steering Committee CSS Working Groups

Steering Committee Industry Chris Decker – Industry PM (d-Wise) Scott Bahlavooni (Biogen Idec) Anne Russotto – (Celgene) Michael Brennan (J&J) Jim Johnson – Optimizing Standards Liaison (Summit Analytical) Susan DeHaven – Non-Clinical Liaison (Sanofi) Mary Nilsson – Standard Scripts Liaison (Eli Lilly) Frederik Malfait – Emerging Technologies Liaison (IMOS Consulting) FDA Crystal Allard – FDA PM Lilliam Rosario Steve Wilson Suzie McCune

Working Group Leadership Teams Emerging Technologies – Frederik Malfait (Roche) – Isabelle deZegher (Paraxel) – Matteo Ditommaso (Pfizer) – Crystal Allard, FDA Liaison Optimizing Data Standards – Jim Johnson (Summit Analytical – Jingyee Kou, FDA Liaison – Steve Wilson, FDA Liaison Standard Scripts – Mary Nilsson (Eli Lilly) – Hanming Tu (Accenture) – Steve Wilson, FDA Liaison Non-Clinical – Susan DeHaven (Sanofi) – Bob Dorsam, FDA Liaison Lot of other volunteers leading projects!

Overview: The development and implementation of data standards has shown significant promise in improving efficiencies in the product submission and review process. However, there are challenges in the interpretation and use of the standards. This working group identifies specific gaps and best practices to enable FDA and industry to maximize the benefits of standards implementation. Optimizing the Use of Data Standards

Optimizing Data Standards Active Projects Traceability and Data Flow ADaM Data Reviewer’s Guide Best Practices Study Data Standardization Plan

Traceability and Data Flow Leaders: Paul Bukowiec, Sandra Minjoe, Tanja Petrowitsch, Natalie Reynolds This project will discuss and define traceability considerations and best practices for study level dataset and integrated datasets conversion for a variety of different data flow scenarios. ODS Projects

Traceability and Data Flow Meeting Accomplishments: – Developed first draft of Study Level Traceability white paper – Noted specific traceability details to be added to current Basic Linear Data Flow white paper – Determined the need to develop a template for the Legacy Data Conversion Plan (mentioned in the new draft FDA Study Data Technical Conformance Guide) ODS Projects

Analysis Data Reviewer’s Guide (ADRG) Leaders: Susan Kenny, Gail Stoner Development of an ADRG template and instructions for industry to consider that will enable consistent and usable ADaM documentation in submissions. ODS Projects

Analysis Data Reviewer’s Guide (ADRG) Accomplished at Meeting – Completed final review of Template – Completed final review of Completion Guideline – Presented poster and expect to receive additional comments. Comments due by MARCH 28. – Began review of one ADRG example By April 30: – Complete review and updates to 2 examples – Finalize ALL documents (template, guidelines, samples) – Post all materials to PhUSE Wiki ODS Projects

Best Practices for Standards Implementation (NEW) Leaders: Mike Molter, Lisa Lyons Goal: develop a set of recommendations for best practices in optimizing the data standards. Each topic will be ~3-5 months duration for delivery of the recommendation Each best practice will have a sub-team First topics include: – Lab Unit Standardization – EPOCH/VISITNUM assignments – USUBJID assignments ODS Projects

Future Best Practices Topics Identified – Programming Documentation – Reference Range Standardization – Unit Standardization Beyond Labs – Trial Design Setup – Treatment Emergent Flags – ARM/ARMCD assignment and standard implementation – Others welcome – Will be a place to identify new topics on Best Practices Wiki Data Optimization: Best Practices

Study Data Standardization Plan (SDSP) – New Project Starting in 2014 – Goal of the Project is to develop a Template to be made available for Industry – Template Model will follow a similar development as the SDTM and ADaM Reviewer’s Guide ODS Project

Overview: The development and implementation of data standards provides a great opportunity to develop standard analyses and displays to support the needs of FDA medical and statistical reviewers. This working group will identify potential standard scripts for data transformation, analyses, and displays. Standard Scripts for Analysis and Programming

P01: Look for existing scripts and store them in the repository - Work on FDA scripts first P02: Define qualification steps for scripts in the repository P03: Maintain and enhance platform (repository) for sharing scripts P04: Create templates and metadata for documenting scripts and coding practices P05: Implement and further develop communication plan for standard scripts P06: Create white papers providing recommended display and analysis including Table, List and Figure shells Refined Projects

Scriptathon – Success!!!! – 26 attendees/15 coders – 13 Scripts developed – Volunteers for the remaining scripts – Organize local and annual events Scriptathon Summary

White Papers – Great Discussion! – Six whitepapers ECG, Vitals, Labs – Central Tendency: finalized in 2013 ECG, Vital, Labs – Outlier/Shifts Adverse Events Demographics, Disposition, Medications Hepatotoxicity PK – One additional white paper planned to be added (QT Studies) – Look for writing support Whitepaper Summary

Continue to build Script Repository – Continue creating code for tables and figures as outlined in white papers – Look for other existing code sharing libraries Continue white paper development – Consider updating the first white paper – Finalize PK white paper this month – Finalize remaining 4 white papers in 2014 – Consider additional white papers to develop Communications – Presentations at various conferences – Implement other ideas to increase awareness Plans for Upcoming Year

Non-Clinical Roadmap and Impacts on Implementation Overview: A need exists to improve nonclinical assessments and regulatory science by identifying key needs and challenges then establishing an innovative framework for addressing them in a collaborative manner. This working group establishes the collaborative framework and identifies and executes projects to support nonclinical informatics and specific implementation solutions for SEND.

Nonclinical Working Group 6 projects with significant accomplishments over the past year -White paper published (3/14): “Interconnectivity of Disparate Nonclinical Data Silos for Drug Discovery and Development” - Manuscript developed on industry use of Nonclinical Historical Control Data - Expansion of SEND Wiki, with QA perspectives on SEND – poster - Compared Clinical vs Nonclinical Study Data Reviewer’s Guide – poster - Development and testing of interorganizational flow of e-data – 2 posters - “How to Design a Custom SDTM Domain for Nonclinical Data”

CSS PhUSE 2014 Theme Developing Collaborations Our Sessions 1.Panel discussion – “How are clinical and nonclinical data coming together in your environment?” 3 presenters shared experiences (vendors, sponsors, consortia) 2.Develop collaborations across PhUSE and others – Interactive discussion on possible projects with Emerging Technologies, IMIeTox, and Transcelerate Goal to increase potential for collaborative new projects 3.Team time Opportunity for NC projects to get feedback from full WG on accomplishments and future directions New project idea triage and action plans 4.Leveraging Deliverables “Table Teams” contributed their experience Socializing the Deliverables

Actions for 2014 AND…….. Turbocharge the SEND Implementation User Group! – New members, WIKI tools, communication subteams

Emerging Technologies Overview: Regulatory science, drug, biologic, and new device development challenged present a unique opportunity to apply underutilized existing technologies and/or new and emerging technologies. This working group provides an open, transparent, pre-competitive forum for the exploration and application of said technologies.

Metadata Definition 30 Leader: Isabelle deZegher No formal meeting Finalize document through TC – Available Apr2014

Review the current draft model Discuss modeling of study parameters/parameter groups, study activities and planned activities Discuss next steps for the RDF model – Do not want it to become another “under-used” representation of structured protocol content ST: Representing PRM/SDM.xml in RDF

Introduce team and concept to the broader community Developed draft metadata for count and summary statistic analysis procedures Identified central tendency, t-test, ANOVA as next analyses to develop Identified strategy for researching publically available existing models Identified alignment needs with the define.xml team and standard scripts repository white paper team ST: Analysis Results Metadata

Summary Great opportunity for FDA and Industry to work together Evolving and changing Typical Challenges of volunteers and time Exciting interactions and discussion

Get Involved See the PhUSE CSS Dashboard for an overview of active projects – More detailed project and working group information is available on the PhUSE Wiki – and working group lead or sign up for a mailing list – uctions uctions