1. Standard Analyses and Code Sharing
(PhUSE Computational Science Working Group)
CDISC Interchange
29 September 2016

2. Working Group Vision/Goals
Leverage crowd-sourcing to improve the content and implementation of analyses for medical research, leading to better data interpretations and increased efficiency in the clinical drug development and review processes.
Establish and maintain a publicly available repository for storing program code to be used as analytical tools for medical research.
Where gaps exist, develop recommendations for analyses and displays in areas that could benefit from crowd-sourcing.
Where gaps exist, develop code for recommended analyses and displays that could benefit from crowd-sourcing (to reside in the repository).

3. Vision: Fill the Gap on Analysis Standards
Data Collection Systems
Observed Datasets
Analysis Datasets
Tables, Figures and Listings
Clinical Data
Flow
Trial Design
PRM
SDTM
ADaM
No TFL Stds Exist
Industry
Standards
Alignment
CDASH
A lot of progress has been made with respect to standardization – mostly in the collection and data space. There’s a gap with respect to analyses and displays. CFAST = Coalition for Accelerating Standards and Therapies
CFAST (Therapeutic Areas)

4. Vision: Shared Reusable Code Library (Script Repository)
Can be a place to share code for ADaM derivations
Repository: Standard Qualified Scripts
Industry
FDA
Academia
Vision of the Script Repository – Reusable code library – Utilizing crowd-sourcing to maintain. All inclusive. Assumes SDTM/ADaM data structure. Currently SAS and R focus but not intended to be limited to those. Getting code associated with the white papers is a current focus. Adding some standard code that FDA medical reviewers use is also a focus.
SAS Cloud
R Studio
Whitepaper Scripts
Contributed Scripts

5. Three Focus Areas, 5 active projects
Script Repository (3 projects)
Script Discovery and Acquisition (SDA, Rebeka Revis, Michael Man)
Repository Content and Delivery (RCD, Gustav Bernard, Andrew Miskell)
Repository Governance and Infrastructure (RGI, Mike Carniello, Hanming Tu)
Analyses and Display White Papers (ADW, Mary Nilsson)
Communication, Promotion, Education (CPE, Jared Slain and Wendy Dobson)

6. New Project – Test Dataset Factory
Background:
Several PhUSE projects develop scripts/concepts that need to be tested with trial datasets
Use of CDISC pilot datasets and/or datasets from team members for testing isn’t sufficient in many cases
Approach and Objective:
Determine test dataset requirements (like # of subjects, observation parameters, etc.)
Implement scripts that create ‘simulated’ SDTM and/or ADaM data sets
Publish datasets and if possible user-configurable scripts
Team:
Project co-lead: Peter Schaefer
Status:
Completed a proof of concept
Working on scope specification and priorities
Need to recruit team members to move ahead
CDISC participation would be appreciated!
Want to use R as the scripting language, this would enable us to easily host the scripts in a cloud-based environment

7. New Project Idea – Best Practices on Data Collection Instructions
Adverse events, concomitant medications, study disposition, reasons for permanent discontinuation from study treatment
Will potentially lead to increased efficiency (site personnel won’t have to learn as many collection methods) and fewer queries (less confusion by site personnel),
Will enable more standardization in data, analyses, displays
For some data domains (e.g., adverse events, concomitant medications, study disposition, reasons for permanent discontinuation from study treatment), sharing best practices on collection instructions will potentially lead to increased efficiency (site personnel won’t have to learn as many collection methods) and fewer queries (less confusion by site personnel), and will enable more standardization in analyses and displays for data common across therapeutic areas.  Unnecessary variations in collection instructions are creating inefficiencies and limiting abilities to fully leverage data standards.  Collection and associated instructions may vary depending on whether the study is early- versus late-stage (as discussed in the February 2016 FDA guidance “Determining the Extent of Safety Data Collection Needed in Late-Stage Premarket and Postapproval Clinical Investigations”), however, reducing the extent of variation would be beneficial for medical research.   
Potential impact on SDTM/ADaM

8. Working Group Accomplishments
5 White Papers finalized
Vital Signs, ECGs, Labs - Central Tendency
Finalized in October 2013, Lead – Mary Nilsson
Non-Compartmental Pharmacokinetics
Finalized in March 2014, Lead - Francois Vandenhende
Demographics, Disposition, and Medications
Finalized October 2014, Lead – Simin Baygani
Vital Signs, ECGs, Labs – Outliers and Shifts
Finalized in September 2015, Lead – Wei Wang
QT Studies
Finalized in March 2016, Lead – Christos Stylianou
How to find final white papers: Go to Click on CS Working Groups,
Click on CS Deliverables Catalog

9. Working Group Accomplishments
AE White Paper out for public review
This is the 2nd and last draft
Comments due 14 October 2016
Expected to be final by end of 2016
Lead – Sheryl Treichel, Nhi Beasley, Mary Nilsson
Upcoming white papers for public review
Hepatotoxicity
Working on Draft 1 for public review
Should be ready approximately October
Lead – Terry Walsh
Please review and recruit reviewers!

10. Working Group Accomplishments
Script Repository has been created
Started in Google Code, now in GitHub
MIT license chosen
Process guidelines developed
Qualification guidelines developed
User-friendly front end developed

11. Working Group Accomplishments
Scripts exist in the repository
Several scripts at various stages (5 Script-athons, plus additional work by the project team)
Focused on creating scripts associated with the displays in the white papers, starting with ADaM data
The specifications for the scripts include assumptions and required ADaM variables
Starting with CDISC pilot data
Received scripts that are part of FDA’s JumpStart service
A couple last year, additional scripts this year

12. Working Group Needs More project team members
Increased participation in white paper reviews – Help recruit!
Use/reference recommendations in existing final white papers!
Forward to any existing standards groups
Link to white papers from Statistical Analysis Plans
Participate in re-usable code development
Write, Test, Qualify, Review, Improve
Keep eyes open for existing scripts that need a public home
Advertise! Advertise! Advertise!

13. How to Participate Sign up for the PhUSE working group mailings
From phusewiki.org, click “Join a Working Group Now”
Standard Scripts Groups
CSS-WG-Standard-Scripts (Entire Working Group)
CSS-WG-Standard-Scripts-WhitePapers (White Paper Project Team)
CSS-WG-Standard-Scripts-Platform (Script Repository)
CSS-WG-SS-WhitePaperReviewers (Notified when a white paper is ready for review)
See wiki pages for each of the projects (