PhUSE CS Final Deliverables Catalog
The PhUSE CS Working Groups bring together academia, industry, technology providers and regulatory agencies including the FDA to collaborate on projects to address unmet computational science needs. This catalog provides a single point of reference for content developed by the CS Working Group projects.
Preliminary recommendations for Traceability using Define-XML Version 2.0: 15-DEC-13: The Define-XML 2.0 Specifications, “Metadata Submission Guidelines” (MSG) V1 and the “ADaM Implementation Guide” V1 documents, describe metadata for SDTM, Analysis Data Sets (ADS) [*1] and Analysis Results. The Define-XML specification document is expected to handle the technical implementation of what is described in less technical terms in implementation guidelines documents; however, it must be recognized that the Define-XML 2.0 Specifications document is reflecting the current version of the Metadata requirements, while the implementation guidelines are not updated yet.
Traceability: Current State Analysis. Version 1.0: 21-AUG-13: Addresses the challenges of integrating and converting data across studies. To define traceability considerations and best practices for study level and integrated dataset conversion for a variety of different data flow scenarios.
Analysis Data Reviewer's (ADRG) Version 1.1: 01-NOV-16: The ADRG provides FDA Reviewers an orientation to the submitted analysis data in a consistent and usable format. The ADRG Work Package includes a ADRG Completion Guidelines, ADRG Template, and examples. This document is referenced in the FDA Study Data Technical Conformance Guide release, March 2015 - click here to view.
Study Data Reviewer's (SDRG) Version 1.2: 01-NOV-16: The SDRG provides FDA Reviewers with additional context for SDTM datasets received as part of a regulatory submission. The SDRG Work Package includes a SDRG Completion Guidelines, SDRG Template, and example SDRGs. This document is referenced in the FDA Study Data Technical Conformance Guide release, March 2015 - click here to view.
Standardizing Data within the Inspection Site Selection Process Final Version: 26-MAY-16: "Guidance for Industry: Providing submissions in electronic format.
CDISC Foundational Standards in RDF Final Version: 30-AUG-15: CDISC has officially taken this on
Metadata Definitions Document Version 1.0: 15-JULY-14: This document contains definitions and example usage for commonly used terms relating to metadata and master data management.
Cloud Services: A Framework for Adoption in the Regulated Life Sciences Industry Version 3.0: 18-NOV-16 : A new edition of the framework was published in November 2016 by the Cloud Adoption Working Group.
SEND Implementation Wiki: Knowledge base for SEND implementers including reference articles, links, modeling basics and FAQs.
The Handling of SEND References in Study Documentation: Recommendations for handling references to SEND in study documentation (e.g. protocol, contracts, etc).
Traceability References: Summarizes and interprets traceability references found in the public domain (e.g. conference papers, CDER Common Data Standards Issues Document, etc).
Emerging Trends & Technologies Working Group:
Alternative Transport: Transport for the Next Generation (word) Version 1.1: 20-MAY-17:
PhUSE initiated The PhUSE Alternate Transport Format Project following discussions between the FDA and PhUSE representatives to come up with some suggestions for the replacement of the venerable (but seriously outdated) SAS® Version 5 (V5) Transport format (hereafter referred to as SAS V5 transport format). This format is the standard for the submission of clinical, nonclinical and analysis datasets to the FDA and other regulatory agencies.
Standard Analyses & Code Sharing Working Group:
2017 White Papers
Screen Shots of the Display Created Using Scripts Contributed by the FDA (PDF) Version 1.1: 23-MAY-17:
Screen Shots of the Display Created Using Scripts Contributed by the FDA (Word) Version 1.1: 23-MAY-17:
Adverse Events White Paper (Word) Version 1.0: 03-FEB-17:
Adverse Events White Paper (PDF) Version 1.0: 03-FEB-17:
2016 White Papers
Analyses and Displays Associated with Thorough QT/QTc Studies (PDF) Version 1.0: 11-MAR-16:
Analyses and Displays Associated with Thorough QT/QTc Studies (Word) Version 1.0: 11-MAR-16:
2015 White Papers
Analyses and Displays Associated with Outliers or Shifts from Normal to Abnormal: Focus on Vital Signs, Electrocardiogram, and Laboratory Analyte Measurements in Phase 2-4 Clinical Trials & Integrated Summary Documents (PDF) Version 1.0: 10-SEP-15:
Analyses and Displays Associated with Outliers or Shifts from Normal to Abnormal: Focus on Vital Signs, Electrocardiogram, and Laboratory Analyte Measurements in Phase 2-4 Clinical Trials & Integrated Summary Documents (Word) Version 1.0: 10-SEP-15:
2014 White Papers
Analyses and Displays Associated to Non-Compartmental Pharmacokinetics - with a Focus on Clinical Trials Version 1.0: 25-MAR-14:
Analyses and Displays Associated with Demographics, Disposition and Medications in Phase 2-4 Clinical Trials and Integrated Summary Documents (PDF) Version 1.0: 07-OCT-14:
Analyses and Displays Associated with Demographics, Disposition and Medications in Phase 2-4 Clinical Trials and Integrated Summary Documents (Word) Version 1.0: 07-OCT-14:
2013 White Papers
Analyses and Displays Associated with Measures of Central Tendency - Focus on Vital Sign, Electrocardiogram, and Laboratory Analyte Measurements in Phase 2-4 Clinical Trials and Integrated Submission Documents (PDF) Version 1.0: 10-OCT-13:
Analyses and Displays Associated with Measures of Central Tendency - Focus on Vital Sign, Electrocardiogram, and Laboratory Analyte Measurements in Phase 2-4 Clinical Trials and Integrated Submissions Document (Word) Version 1.0: 10-OCT-13:
Nonclinical Topics Working Group:
Journal Article: Graphical display of histopathology data from toxicology studies for drug discovery and development: An industry perspective: Histopathology data comprise a critical component of toxicology studies and are typically presented as organ-specific incidence counts, tabulated in study reports. Various software applications are available to convert histopathology data into graphical displays for visual presentation. Intra-industry surveys were conducted within the FDA PhUSE Nonclinical Working Group and at the 2015 European Society for Toxicologic Pathology annual meeting regarding the use and limitations of graphical displays of histopathology data. This article discusses the outcome of the surveys in the context of visual cues, use-cases and the value of cross-domain visualisations. This article was published in the Journal: Regulatory Toxicology & Pharmacology, Volume 82, December 2016, Pages 167-172.
Investigating Endpoint Modeling Biomarkers, ADA Data & Immunophenotyping Version 1.0: 03-JAN-17: The Investigating Endpoint Modeling PhUSE project team embarked on an investigation in 2015-2016, to determine suitable ways to model endpoints, which are not modelled in the SEND Implementation Guide (SENDIG V.3.0) and development a methodology for the inclusion of data such as biomarker, anti-drug antibody (ADA) and immunophenotyping results. This paper describes a recommendation for a methodology to include data such as biomarkers into a SEND dataset and the decision making process utilised. The paper presents possible best practices for inclusion of unmodeled endpoints with a consistent methodoloy.
Journal Article: Interconnectivity of Disparate Nonclinical Data Silos for Drug Discovery and Development 22-APR-14: Pharmaceutical research and development generates enormous amounts of nonclinical and clinical data related to safety and efficacy and the ability to manage and utilize these data is critical for discovering and developing new drugs. Information systems exist that store and analyze relationships among seemingly disparate data sets (i.e. data silos); however, to fully utilize the potential of these informatics systems, it is necessary to define basic parameters about the data and to develop concepts regarding "interconnectivity" or relationships among disparate data sets. This article was published in the Therapeutic Innovation & Regulatory Science, DIA Scientific Journal, 2014. Click here to view.
Roadmap for Nonclinical data Standards and Elements to Improve Data Access: Identifies points to consider when implementing Nonclinical Standards, sets priorities for Nonclinical data types and considerations for future Nonclinical Standards development. Documents key Standards resources.
Optimizing Use of Data Standards Working Group:
Study Level Traceability in a Non Linear Data Flow. Version 1.0: 01-OCT-14: This white paper will focus on traceability in a non-linear data flow, resulting from the conversion of legacy data to CDISC standards. In February, 2014, the FDA released the Draft Study Data Technical Conformance Guide – Technical Specifications Document1. In the Draft Study Data Technical Conformance Guide.
Best Practices for Data Sizing: Provides recommendations managing the length of character variables in a submission, handling SAS transport files that exceed the maximum allowable size and documenting split domains in define.xml.
Best Practices for Data Standards Implementation, Assigning VISITNUM to Unplanned Visits and Assigning EPOCH to Observations 06-MAR-14: This document provides recommendations for assigning VISITNUM values to unplanned visits as well as EPOCH to observations when dates are missing, partial or during a period which is not a planned element in the trial. The document focuses on specific use cases and provides recommendations for managing solutions.
Traceability, Best Practices for Linear Data Flow: Describe traceability needs pertinent to regulatory agency review of electronic clinical data for collected data to tabulation data (SDTM) to analysis datasets to analysis results/output.
Linked Data & Graph Databases Working Group
Introduction of Clinical Development Design (CDD) Version 1.0: 01-NOV-16: The Clinical Development Design (CDD) Framework encompasses design decisions and their attributes in clinical development programs and trials. These decisions rely on consolidating, analyzing, weighing, and prioritizing a multitude of information from guidance, past experience, expert advice, and real world evidence. This wealth of information is typically captured in an unstructured format, in the form of clinical development plans, protocols, documents, and presentations. The CDD Framework aims to provide structure and rigor to the design of clinical development programs consisting of clinical trials and clinical research programs. A cross- industry initiative under the auspices of PhUSE, with participants from industry, FDA, and academia, is working on an information model to underpin clinical development program design