PhUSE Computational Science Symposium Working Groups An Experiment in Collaboration

1. PhUSE Computational Science Symposium Working Groups An Experiment in Collaboration

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

3. Old Paradigm FDA Please tell us what to do

4. Paradigm Shift FDA CDISC Pharma CROs Academia Vendors

5. CSS Timeline

6. What CSS WGs Are?

7. What CSS WGs are Not

8. CSS Working Groups

9. 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

10. 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!

11. Optimizing the Use ofData Standards 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.

12. Optimizing Data Standards Active Projects

13. ODS Projects Traceability and Data Flow • Leaders: Paul Bukowiec, Sandra Minjoe, TanjaPetrowitsch, 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.

14. 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)

15. 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.

16. 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

17. 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

18. Data Optimization: Best Practices • 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

19. ODS Project • 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

20. Standard Scripts for Analysis and Programming 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.

21. Refined Projects • 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

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

23. Whitepaper 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

24. Plans for Upcoming Year • 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

25. 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.

26. 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”

27. CSS PhUSE 2014 ThemeDeveloping Collaborations • Our Sessions • Panel discussion – “How are clinical and nonclinical data coming together in your environment?” • 3 presenters shared experiences (vendors, sponsors, consortia) • 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 • Team time • Opportunity for NC projects to get feedback from full WG on accomplishments and future directions • New project idea triage and action plans • Leveraging Deliverables • “Table Teams” contributed their experience Socializing the Deliverables

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

29. 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.

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

31. ST: Representing PRM/SDM.xml in RDF • 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

32. ST: Analysis Results Metadata • 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

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

34. Get Involved • See the PhUSE CSS Dashboard for an overview of active projects • http://www.phuse.eu/CSS-dashboard.aspx • More detailed project and working group information is available on the PhUSE Wiki • http://www.phusewiki.org/wiki/index.php?title=PhUSE_Wiki • Email and working group lead or sign up for a mailing list • http://www.phusewiki.org/wiki/index.php?title=Listbox_Instructions