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

2. What is PhUSE? Pharmaceutical Users Software Exchange Mission:
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

3. Please tell us what to do
Old Paradigm
FDA
Please tell us what to do

4. Paradigm Shift
FDA
CDISC
Pharma
CROs
Academia
Vendors

5. CSS Timeline 2008: PhUSE and FDA collaborate on Wiki
2009: FDA forms CSC
2010/11: FDA hosts first two CSC meetings
2012: First Annual CSS Meeting
2013/14: Annual CSS Meetings

6. What CSS WGs Are? Implementation Incubator Collaboration
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

7. What CSS WGs are Not Policy Standards Commercial
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

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

9. Steering Committee FDA Crystal Allard – FDA PM Lilliam Rosario
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 of Data 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
Traceability and Data Flow
ADaM Data Reviewer’s Guide
Best Practices
Study Data Standardization Plan

13. ODS Projects 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.

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 Theme Developing 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
More detailed project and working group information is available on the PhUSE Wiki
and working group lead or sign up for a mailing list