PhUSE Computational Science Symposium

Working GroupsAn Experiment in Collaboration

What is PhUSE?

Pharmaceutical Users Software Exchange• Global group of programmers, statisticians, and data

scientists • Vendor neutral, Inclusive, and Open• www.phuse.euMission: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

FDA

Pharma

CDISC

Vendors

CROs

Academia

CSS Timeline2013/14: 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 processesIncubator

•Open forum for sharing ideas across FDA, Industry, and other organizations•Provide platforms (wikis, code libraries) for sharing informationCollaboration

What CSS WGs are Not

•Projects do not create, define and/or recommend policy or guideline changes•FDA individuals provide input onlyPolicy•CDISC, HL7 and other SDOs create standards;•CSS Working Groups tackle implementation and best practices around standardsStandards

•Projects are not a place to ‘market’ technology•Open collaboration in a non-competitive environment

Commercial

Optimizing Use of Data Standards

Emerging Technologies

Standar

d Scri

pts f

or

Re

por

ti

ng a

nd

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 ofData 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 ThemeDeveloping Collaborations

Our Sessions1. 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.

30

Metadata Definition

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– 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