Standard Analyses and Code Sharing Working Group Project Updates US CSS 20 March 2017

SDA: Script Discovery and Acquisition Project Description Discover, acquire and review scripts to be stored in the repository with adequate metadata to describe the scripts Project Leads Rebeka Revis Alfredo Rojas

P01 - SDA: Script Discovery and Acquisition Project Accomplishments JumpStart scripts have been contributed A couple in 2015, additional scripts early 2016, modified scripts early 2017 First draft of scripts have been tested, a couple modified scripts have been tested White paper with JumpStart screen shots – hope to finalize in March 2017 Non-clinical scripts, scripts related to data handling, and an interactive safety review have also been contributed

SDA: Script Discovery and Acquisition Adverse Event Severity (AE_Severity) Accenture: Alfredo Rojas Novo Nordisk: Lina Ulkjær Adverse Event Toxicity (AE_Toxicity) Demographics (DemographicsGeneral) Disposition (DispositionGeneral) Exposure (ExposureGeneral) Liver Labs (LiverLabsGeneral) MedDRA at a Glance (MedDRA_at_a_Glance – ae_meddra_w_flag_generation.sas) The list above gives the script and the script tester(s).

SDA: Script Discovery and Acquisition Project Next Steps Continue testing modified JumpStart Scripts (need additional volunteers) Will continue to monitor for additional scripts that may make sense for the PhUSE Repository We also need a JumpStart representative to help us respond to reviewer comments.

P02 - RCD: Repository Content and Delivery Project Description Develop and enhance scripts under a defined qualification process to ensure the usability and quality of the standard scripts Project Leads Gustav Bernard Andrew Miskell

RCD: Repository Content and Delivery Team Distributed in 2 Target Teams Target Team 1: Nancy Brucken Target Team 2: Alex Ford Each Team worked on Separate Target Deliveries / Outputs

RCD: Repository Content and Delivery Project Accomplishments GitHub script repository https://github.com/phuse-org/phuse-scripts/ Project Programming Guidelines http://www.phusewiki.org/wiki/index.php?title=WG5_P02_Programming_Guidelines Streamlined Qualification Process http://www.phusewiki.org/wiki/index.php?title=WG5_Project_02#Qualification_Process https://prezi.com/qsc7hr8j2h8b/2015-phuse-cs-qualification-process-wg5-p02/?utm_campaign=share&utm_medium=copy Central Tendency package Qualification Completed 6 Recommended displays in CT White Paper https://github.com/phuse-org/phuse-scripts/blob/master/whitepapers/WPCT/TODO.md

RCD: Repository Content and Delivery Project Next Steps Central Tendency Shifts Scripts for SAS only Scripts less Macro dependent (Stand alone program for easy download and use) 2017 FDA Representative: Dr. Qing Zhou

P03 - RGI: Repository Governance and Infrastructure Project Description: Establish the basic structure and management of the repository. Define and enforce existence of required metadata for scripts Manage users and projects in the repository Project Leads: Mike Carniello Hanming Tu

RGI: Repository Governance and Infrastructure Project Accomplishments MIT license chosen: https://github.com/phuse-org/phuse-scripts/blob/master/LICENSE.md Qualification guidelines developed: http://www.phusewiki.org/wiki/index.php?title=WG5_Project_02#Qualification_Process User-friendly front end developed: https://github.com/phuse-org/phuse-scripts/wiki/Simple-Index Repository has been updated to have a place to store scripts developed by other groups More people have joined the development team (28 now): https://github.com/orgs/phuse-org/people

RGI: Scripts Contributed Scripts contributed by other groups FDA: https://github.com/phuse-org/phuse-scripts/wiki/JumpStart-Scripts Non-clinical: https://github.com/phuse-org/phuse-scripts/tree/master/contributed/Nonclinical Data Handle: https://github.com/phuse-org/phuse-scripts/tree/master/lang/SAS/datahandle Spotfire Templates: https://github.com/phuse-org/phuse-scripts/tree/master/contributed/Spotfire

RGI: Scripts Developed Scripts developed by volunteers 6 Scriptathons (plus additional work by project members) resulting in several scripts at various stages 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 Scripts developed based on white paper Central Tendency package Qualification Completed: 6 Recommended displays in CT White Paper

RGI: Repository Governance and Infrastructure Project Next Steps Continue maintaining repository structure Continue managing users and accesses to the repository Define how to use YML for script metadata Define and explore script test environment

P07 - CPE: Communication, Promotion, and Education Project Description Conceptualize Efficient Ways to Communicate Working Group Progress and Results Project Leads Jared Slain Wendy Dobson

CPE: Communication, Promotion, and Education Project Accomplishments Presentations: List of past/present/future working group member presentations on PhUSE Wiki Presentations JumpStart scripts – 2016 PhUSE Annual Conference GitHub User Guide – 2017 CSS

CPE: Communication, Promotion, and Education Project Accomplishments cont’d Compiled ongoing list of events for promoting WG Use of social media to advertise White Papers As co-lead, Wendy provides streamlined integration with PhUSE Office

CPE: Communication, Promotion, and Education Project Next Steps Keep project page on PhUSE Wiki updated Find people already going to events to present/promote working group Work with White Papers project to enhance White Paper visibility Training Material

P08 - ADW: Analysis and Display White Papers Project Description This project includes the development of white papers that provide recommended Tables, Figures, and Listings for clinical trial study reports and submission documents. The intent is to begin the process of developing industry standards with respect to analysis and reporting for measurements that are common across clinical trials and across therapeutic areas. Script developers could then create scripts consistent with the recommendations for all to use, improving efficiency and safety signal detection. Project Lead – Mary Nilsson

ADW: Analysis and Display White Papers How to find final white papers: Go to www.phuse.eu, Click on Working Groups, Click on CS Deliverables Catalog Project Accomplishments 6 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/QTc Studies Finalized in March 2016, Lead – Christos Stylianou Adverse Events Finalized February 2017, Lead – Mary Nilsson, Nhi Beasley, Sheryl Treichel

ADW: Analysis and Display White Papers Project Next Steps AE White Paper follow-up tasks Gender- and Pediatric-specific MedDRA lists Process for Grouping MedDRA terms Work on 4 new white papers Hepatotoxicity Questionnaire data Treatment-emergent definitions Adverse events of special interest Work on version 2 of a couple white papers Demographics/Dispostion/Medications Labs/Vitals/ECGs

Analysis and Display White Papers Project Team Version 1 Version 2 Public Review Published Public Review Vital Signs, Labs, ECG – Central Tendency Oct 2013 Q4 2017 Non-Compartmental PK March 2014 Demographics, Disposition, Medications Oct 2014 Q3 2017 Outliers / Shifts Sept 2015 QT/QTc Studies March 2016 Adverse Events Feb 2017 Treatment-Emergent Definitions Hepatotoxicity Questionnaires Events of Special Interest

ADW: Analysis and Display White Papers Project Next Steps (continued) Communication and Education Will network with the CPE project team Will likely focus on “Core” package (demographics, disposition, medications, AEs, labs, vitals, ECGs) Will likely include multiple approaches (live educational and informational sessions, webinars, video clips, etc.) Please help – anyone attending a conference can cover a roundtable or poster – we will help!

P09 - TDF: Test Data Factory Project Background: Several PhUSE projects develop scripts/concepts that need to be tested with trial data sets Use of CDISC pilot datasets and/or data sets from team members for testing isn’t sufficient in many cases Project Approach and Objective: Determine test dataset requirements Short versus long term approach: Create test data sets from existing study data Implement scripts that create ‘simulated’ SDTM and/or ADaM test data sets Publish datasets, and if possible, user-configurable scripts Project co-lead: Peter Schaefer (pschaefer@vca-plus.com)

TDF: Test Data Factory Project Accomplishments Project team has been established We still can use additional team members Decided to update existing CDISC pilot data to be consistent with current SDTM/ADaM standards with two objectives Produce useful results quickly Establish knowledge base for issues around ‘simulating’ test data sets Update of SDTM domains in progress Some domains are done (trial design, DM, …) See poster PP16 for more information

TDF: Test Data Factory Project Next Steps Continue to recruit project members Short term: Complete update of CDISC Pilot data sets and publish Mid term: Create Proof of Concept for ‘simulated’ test data sets