Development of Standard Scripts for Analysis and Programming PhUSE Computational Science Working Group Update 24 November 2015

Working Group Goal Establish a platform for the collaborative development of program code to be used as analytical tools for clinical trial research, reporting, and analysis Includes recommendations for analyses, tables, figures, and listings Process and guidelines for documentation and management of scripts Harness data standards whenever feasible

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)

Vision: Shared Reusable Code Library (Script Repository) 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.

Three Focus Areas, 5 active projects Script Repository (3 projects) Script Discovery and Acquisition (SDA, Adie Bonwick, Aiyu Li) Repository Content and Delivery (RCD, Dante Di Tommaso, Peter Schaefer) Repository Governance and Infrastructure (RGI, Mike Carniello, Hanming Tu) Analyses and Display White Papers (ADW, Mary Nilsson) Script Repository (4 projects) Platform, process, development, access, validation, legal considerations, etc. White Papers on Analyses and Displays (1 project) Communications (1 project) P01: Look for existing scripts and store them in the repository Adrienne Bonwick and Aiyu Li P02: Define qualification steps for scripts in the repository Dante Di Tommaso P03: Maintain and enhance platform (repository) for sharing scripts Mike Carniello/Hanming Tu P04: Legal ownership and issues in open source repository Sally Cassells P05: Create templates and metadata for documenting scripts and coding practices Jean-Marc Ferran/Eric Sun P06: Refine process for creating and editing scripts in Google Code Closed, any remaining tasks moved to Project 03 P07: Implement and further develop communication plan for standard scripts Dirk Spruck P08: Create white papers providing recommended display and analysis including Table, List and Figure shells Mary Nilsson Communication, Promotion, Education (CPE, Dirk Spruck)

Working Group Accomplishments Script Repository has been created Started in Google Code, now in GitHub 5 Scriptathons Scripts exist in the repository MIT license chosen Process guidelines developed Qualification guidelines developed User-friendly front end developed

Working Group Accomplishments 4 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

Deliverables for Public Review White Paper just went through public review TQT Studies Lead - Christos Stylianou Upcoming white papers for public review Adverse Events Working on Draft 2 for public review, Lead – Sheryl Treichel Hepatotoxicity Working on Draft 1 for public review, Lead – Terry Walsh

Goal Between CSS 2015 and CSS 2016 Create a “full package” for the Vital Signs, ECGs, Labs Central Tendency White Paper Updated white paper with ADaM specifications Qualified code for the displays in the white paper Agreed upon structure for storing scripts Agreed upon meta-data for scripts See the “Boxplot Challenge” http://www.phusewiki.org/wiki/index.php?title=WG5_Box_plot_challenge

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 Sign-up for Scriptathons (e.g., at 2016 CSS) Participate in the boxplot challenge! Keep eyes open for existing scripts that need a public home Advertise! Advertise! Advertise!

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 (www.phusewiki.org)