1. PhUSE Computational Science Working Groups Solutions Through Collaboration

2. PHUSE CS OVERVIEW

3. Paradigm Shift

4. Computational Science Collaboration Mission: To provide an open, transparent, and collaborative forum in a non-competitive environment in which Academia, Regulators, Industry, and Technology providers can address computational science needs in support of product development and regulatory review, ultimately bringing safe and effective products to those who need them.

5. CS Collaboration Framework Working Groups Symposium Computational Science Collaboration

6. CS Working Groups Steering Committee Optimizing Use of Data Standards Emerging Technologies Standard Scripts for Reporting and Analysis Non-Clinical Roadmap and Implementation Semantic Technology

7. 2016 CSS WRAP UP

8. CSS 2016 Highlights Over 300 attendees – SOLD OUT! Over 50 FDA attendees/2 from PMDA Lively panel discussion Engagement in every project Networking with new and old colleagues Great food!

11. OPTIMIZING THE USE OF DATA STANDARDS

12. CSS 2016 Project Summary  Standards Implementation Nuances (by version)  Brain-storming sessions focused on Standards Implementation and Standards Nuances  Results of sessions will be used to scope the project  Possible project with CDISC for SDTM/ADaM FAQ  Define v2.0 Implementation & Style Sheet Recommendations  Two projects identified and in the process of determining all co-leads  Define-XML 2.0 Implementation, "Completion Guidelines" document, focusing on best practices for content and granularity  Define-XML 2.0 Stylesheet Recommendations, scope to be clarified by team  Study Data Standardization Plan (SDSP)  Outstanding questions answered & deliverables to be updated  Deliverables to be sent to FDA Champion by end of March  Deliverables for public review with Technical Conformance Guide updates

13. CSS 2016 Project Summary  Legacy Data Conversion Plan & Report (LDCP)  Updated SDRG template will be sent to FDA for FDA PhUSE Working Group Review  SDRG Completion Guidelines and Example Document requires updates  Working group lead to schedule meetings with team members  Reviewer’s Guide & Define.xml  Reviewed notes and questions from discussions over the last year with the broader group  Core team reviewed and edited introductory sections of white paper and paper outline  Standardizing Data within the Inspection Site Selection Process  Analysis of gaps between FDA expectations and CDISC standards near completion  Reps from CDISC indicated they will consider new standards for this  PhUSE Standard Scripts group indicated they will consider standard specs and code for this

14. Roundtable Discussion Summary Working group met on Tuesday afternoon to discuss pertinent topics and generate ideas for projects not already defined

15. Standards Scripts for Analysis and Reporting

16. What We Did Updated the whole group about our vision, motivation, and progress Had the following breakout sessions: –Whitepapers Discussed displays associated with adverse events, questionnaire data, hepatotoxicity –Repository Reviewed Git and Github Reviewed qualification process Reviewed FDA JumpStart scripts in the repository Reviewed the front-end of repository – index page Discussed name convention, version control and the goals Conducted workshop on github and the repository Met with Results Analysis Metadata WG and formed a collaboration on creating a analysis result

17. Goals in PhUSE Year 2017 Promote and Present FDA JumpStart content Develop and present Central Tendency package moving through the qualification process Develop and present traditional vs analysis result metadata driven program using central tendency. Continue development of 4 analysis and display white papers

18. Possible new projects Test Data Curation –In order to have a good tests, we need to have test data sets containing different “issues” so that we could test scenarios that we plan to test –We need to have SDTM and ADaM data sets Mapping the whitepapers and scripts –We need to create technical documents from the whitepapers to define what type of scripts that we need –We need to create the mapping between the whitepapers and scripts at the variable level 18

19. NON-CLINICAL IMPLEMENTATION AND ROADMAP

20. CSS2016: Nonclinical Working Group Outcomes Breakout Attendance and Action better than ever – over 60 attendees representing FDA, PMDA, Pharma, CROs and software vendors. – Nine project teams will go forward into the coming “PhUSE Year” to answer their highest priority data challenges Highlights – Collaboration Poster Award for the Nonclinical SDRG! – Assessment of current state of SEND-readiness in Industry Team conclusion: progress but room for improvement New Project Teams formed to tackle emerging implementation issues – Extensive stakeholder discussions on Data Visualization and Analysis Multiple needs identified resulting on several key projects: one for visualization, one for analysis and one for script development

21. Nonclinical Projects Proposed for the Coming Year SEND Implementation – SEND Implementation User Group – Nonclinical Study Data Reviewer’s Guide – Annual SEND Implementation Status Survey – Submission Data Consistency – Test Submission Forum Visualization and Analysis – Application of SEND Data for Analysis – Visualization of Group Differences in Histopathology Data – Nonclinical Analysis Scripts

22. CSS 2016 – Wrap up Ian Fleming Geoff Low Emerging Trends and Technologies

23. Working Groups Alternate Transport Formats Cloud Adoption Data Transparency Data Visualisation Statistical Computing Environments

24. Alternative Transport Formats Achieved: –Worked on a set of criteria for evaluating transport formats –Discussed transport and content issues Target: –Finalise Criteria –Carry out Survey to prioritise criteria –Release white paper on evaluation of existing and new transport formats

25. Cloud Adoption Achieved –Discussed Existing Framework document –Discussed Questions posed by EMA –Defined path for expansion and socialisation of Existing Framework Targets –Update Framework to include Auditor section –Update Framework to incorporate data location –Develop Q&V section

26. Data Transparency Achieved –Review EMA Policy 0070 –ADaM De-identification Scenarios extreme values, imputed dates Targets –Blog Post on EMA 0070 –Questionnaire for previous downloaders –Release ADaM guidance for Public review

27. Data Visualisations Achieved –Discussed and agreed future direction of Group Targets –Risk-Based Monitoring & Data Visualisations –Implementations of Data Visualisations –Safety Graphics –Technology Comparisons –Interactive vs. Static Visualisations

28. Statistical Computing Environments Achieved –Developed framework for describing user requirements for SCE (Acquire, Transform, Analyze, Visualize, Deliver) –Created list of requirements within this framework. Targets – Distill notes further and finalize framework – Request industry to share user requirement documents that they have developed – Develop best practices as precursor to user requirements – Develop visual representation of SCE, clearly defining scope – Develop and publish user requirements

29. CSS 2016 Project Summaries Semantic Technology Working Group

30. Workshop: Semantics 101 for Pharma An introduction to Linked Data and the Semantic Web Over 50 attendees Groundwork for Semantic Technology Projects. Future Offerings: PhUSE CSS – EU Annual Conference, Barcelona Marc Andersen, Tim Williams

31. Analysis Results & Metadata Project Deliverables Due end of June, 2016: White Paper, RDF Data Cube Tech. Specification, R Package. Collaboration Standard Scripts, Use Cases –R Package Hosting. –Code base and data for use cases. Plans for 2016 Use cases from Clinical Data Review Template (FDA suggestion). Cloud solution. Marc Andersen, Tim Williams

32. Clinical Program Design White Paper Review and Development Reviewed original CPD suggestions. Reviewed and added tools for ST design in other industries. Reviewed sections and comments. Added Early Experiences with Design Tools. Schedule Finish all WP sections and reviews : March – June 2016 Send WP for PhUSE review by July 1, 2016 Tool Development : June 2016 – April 2017 –Test CMAP and Neo4j for Design Activities. –Build Instructional materials for tools. –Validate nodes for Design Activities. Mary Banach, Laszlo Vasko

33. Regulations to RDF (REG2RDF) Project Deliverables (by March, 2016) Key words for 21 CFR, reviewed by the FDA CDER/OSI. Web-based search 21 CFR. C-map graph representations of two of the 21 CFR sections. Plans for 2016 Interactive domain expert review tool for 21 CFR key words. Link 21 CFR regulation to: –Relevant FDA guidances. –Regulations from other health authorities (e.g. EMA, ICH, PMDA, KMDA, and etc.). –Geographic locations. Change Management and Version Control. Cloud storage for public accessibility. Mitra Rocca

34. Use Cases For Linked Data Project Kick Off Collected Use Cases. Collaboration Optimizing the Use of Data Standards. –Additional Use Cases. Plans for 2016 2-3 virtual round tables. Collate Use Cases, Draft White Paper. Consider development of proof of concept. Scott Bahlavooni, Christine Fleeman

35. 2016 EUROPEAN CSS

37. Why a European CSS? Collaboration and innovation are global European colleagues make significant contributions to the CS Collaboration –Steering Committee –Working Group Co-Leads –Project Co-Leads > 20% of US CSS attendees from Europe

38. European CSS Overview June 21-22 in Basel, Switzerland Focused on a subset of CS projects Free to PhUSE members –Only 120 spots available –April 1: Registration opens to Working Group members –April 18: Registration opens to general public

39. European CSS Agenda Tuesday, June 21 –14:00-16:00: Opening Session –16:00-17:00: Working Group Breakout and Introductions –17:00-18:30: Semantics 101 for Pharma Workshop Wednesday, June 22 –9:00-15:00: Working Group Breakout Sessions –15:00-17:00: Working Group Wrap Up and Closing Remarks

40. European CSS Projects Describe and develop requirements for an ideal SCE SCE Experiences Finalise evaluation criteria survey Alternative Submission Transport Formats Continued development of ADaM de- identification rules De-Identification of ADaM Review of ongoing Working Group projects Non-Clinical: SEND Implementation Joint CDISC/PhUSE project to address SDTM implementation questions SDTM Implementation FAQ Define optimal to enable new ways of working and increase collaboraprocessestion PhUSE Future Forum: Process Optimization

41. Questions