PhUSE CDASH2RFD TC May 31, 2013 Gary Walker, Quintiles Rhonda Facile, CDISC

1. PhUSE CDASH2RFD TC May 31, 2013 Gary Walker, Quintiles Rhonda Facile, CDISC

2. Slide Number One Agenda • The need for CRF Standards • Background • Approach • Current Deliverables • Q&A

3. CRFs Without Standards (CDASH)

4. Data Without Standards… Name for Subject ID is never the same Name for demography dataset is variable??? Study #2 – dmg.xpt Study #1 – demo.xpt Study #3 – axd222.xpt Study #4 – dmgph.xpt Gender or Sex, what will this study use? Is Sex Male or Female, M or F, 1 or 2? Adapted from slide courtesy of Armando Oliva, M.D. and Amy Malla, FDA

5. Data Collection With CDASH (paper)

6. Basic Concepts of CDASH • Minimal ‘core’ dataset for clinical research • Standardize the questions/fields on CRFs • Standardize the variables and harmonize with SDTM (CDASH is a subset of SDTM) • Collect data using standard CDISC controlled terminology that maps into SDTM • Implementation help • Best Practice recommendations • Implementation recommendations http://www.cdisc.org/cdash

7. Catalyst FDA CRITICAL PATH INITIATIVE: STREAMLINING CLINICAL TRIALS Creating Innovative and Efficient Clinical Trials and Improved Clinical Endpoints 45. Consensus on Standards for Case Report Forms.Clinical trial data collection, analysis, and submission can be inefficient and unnecessarily expensive. A wide array of different forms and formats are used to collect clinical trial information, and most data are submitted to the FDA on paper. Differences in case report forms across sponsors and trials creates opportunities for confusion and error. Standardization of the look and feel of case report forms could reduce these inefficiencies and also help accelerate progress toward electronic data capture and submission. • “Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products”, Critical Path Opportunities List, March 2006, page L-10.

8. CDASH Project Snapshot • 16 (+2) Safety data domains developed • Consolidated document posted for public review in May 2008 • Received over 1800 comments from 46 companies, institutions and agencies. • All 3 ICH regions were represented in the public comment process • US • Europe • Japan • V1.0 published in October 2008 • Streamlines data collection at investigative sites - addresses Critical Path Opportunity #45 • Continuation of ACRO’s Initiative • Started October 2006 • Supported by a collaborative group of 17 organizations • Initial Core Team of 16 members managed • 11 working groups • Composed of between 8-40 volunteers

9. CDASH Project Snapshot • CDASH User Guide became available to members in 2012, including • User Guide documentation • CDASH content in ODM • CDASH example CRF library • Therapeutic Area CRFs are being developed, including • Alzheimers • Cardiovascular • Oncology • CDASH guidelines to address regulatory requirements (DILI, E2B) are being developed • Version 1.1 published January 2010 to address • New data elements added • A few corrections • Question Text and Prompt • Conformance Rules • CDASH and the analogous NCI CRFs are being harmonized • Current Leadership Team manages several CDASH Sub-teams with participation of ~50 team members

10. Section 1.1 of CDASH v1.1 Purpose of CDASH

11. Principles • Ensure that SDTM “required” elements are addressed directly or indirectly • Be “standard” but flexible to allow customization within defined limits • Focus on CRF Content, not CRF Layout • Limit variables to required and necessary • Comply with regulatory requirements • Reduce redundancies • Facilitate use of standards by all users • Be appropriate for use both pre and post approval studies • Allow consistent and efficient data collection/storage/transmission and analysis

12. CDASH Standards CDISC CDASH V 1.1 2010 18 Domains UG V1.0 published in 2012 Mapping to SDTM CRF Examples CDASH in ODM

13. Metadata Tables • Information/rationale and instructions on how to implement the CRF data collection fields Short prompt for the data collection field; could be used as the CRF label BRIDG Mapping • Defines the Data collection field Full question text for the data collection field. Either question text or prompt can be used on the CRF • Instructions for the clinical site on how to enter data on the CRF. Includes controlled terminology SDTM Variable Name OR CDASH Variable Name Designations HR Rec/Cond Optional

14. Section 4.3 of CDASH v1.1 Overview of CDASH Tables

15. Section 1.2.1 of CDASH v1.1 General Notes

16. Section 1.2.1 of CDASH v1.1 Data collection mechanisms

17. Section 1.2 of CDASH v1.1 CDASH Standard Document Contents

18. CDASH User Guide Contains implementation examples, including CDASH to SDTM mappings, CDASH ODM files and a library of example CRFs that have been created in several different data collection systems, including paper examples.

19. Core Designations • Highly Recommended (HR): A data collection field that must be on the CRF (e.g., a regulatory requirement) • Recommended/Conditional (R/C): A data collection field that should be on a CRF based on certain conditions (e.g., complete date of birth is preferred, but may not be allowed in some regions, AE time should only be captured if there is another data point with which to compare it) • Optional (O): A data collection field that is available for use

20. FAQs • Yes/No questions are preferred over “check all that apply” format • Keep response boxes (Yes/No/NA) in a standard format consistent across CRFs • Use unambiguous date format DD-MMM-YYYY • Create convention to capture Unknown portions of the date-DO NOT IMPUTE! • Use 24 hour format for times • Do not include manually calculated items on the CRF (e.g. BMI) if the raw data are collected

21. Current CDASH Subteam Projects • Development of PK CRF content • Development of Device CRF content • Working on update to CDASH 2.0 (new version of standard) • Working on update to CDASH UG • Liaising with TA teams for Alzheimer’s Disease, Asthma, Diabetes. (Future TA work TBD) • Looking at development of CDASH Model • Expanding CRF Library • Adding Terminology guidance for mandatory codelists in the next version of CDASH (2.0)

22. CDASH Overview Q&A