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PhUSE CDASH2RFD TCMay 31, 2013
Gary Walker, QuintilesRhonda Facile, CDISC
© CDISC 2013
Slide Number One
Agenda
• The need for CRF Standards• Background• Approach• Current Deliverables• Q&A
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© CDISC 2013
CRFs Without Standards (CDASH)
© CDISC 2013
Data Without Standards…
ID GENDER
A1 Male
A2 Male
A3 Female
A4 Female
A5 Male
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SUBJID SEX
0001 M
0002 F
0003 F
0004 M
0005 F
USUBID SEX
00011 0
00012 1
00013 1
00014 0
00015 1
PTID GENDER
0001 1
0002 1
0003 2
0004 2
0005 1
Study #2 – dmg.xpt
Study #3 – axd222.xpt
Study #4 – dmgph.xpt
Name for Subject ID is never the
same
Name for demography
dataset is variable???
Is Sex Male or Female, M or F, 1 or 2?
Gender or Sex, what will
this study use?
Adapted from slide courtesy of Armando Oliva, M.D. and Amy Malla, FDA
Study #1 – demo.xpt
© CDISC 2013
Data Collection With CDASH (paper)
© CDISC 2013
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
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Catalyst
• FDA CRITICAL PATH INITIATIVE: STREAMLINING CLINICAL TRIALS
Creating Innovative and Efficient Clinical Trials and Improved Clinical Endpoints
45. Consensus on Standards for Case ReportForms. Clinical trial data collection, analysis, andsubmission can be inefficient and unnecessarilyexpensive. A wide array of different forms andformats are used to collect clinical trial information,and most data are submitted to the FDA on paper.Differences in case report forms across sponsors andtrials creates opportunities for confusion and error.Standardization of the look and feel of case reportforms could reduce these inefficiencies and also helpaccelerate progress toward electronic data captureand submission.
“Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products”, Critical Path Opportunities List, March 2006, page L-10.
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
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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
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© CDISC 2013
Purpose of CDASH
• Initial scope limited to most commonly collected data• These CRF standards apply across most therapeutic areas and
phases of clinical development (I-IV)
Develop CRF content standards for a basic set of global industry-wide CRF fields to support clinical research
Maximize re-use of data, CRFs, programming, etc.
Increase transparency and traceability in the data
Support data repository and data sharing
• CDASH used as a content standard to harvest data from electronic health records (Healthcare Link)
Support integrating research into clinical care workflow
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Section 1.1 of CDASH v1.1
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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
CDISC CDASH V 1.1 2010
18 Domains
UG V1.0 published in 2012
Mapping to SDTMCRF ExamplesCDASH in ODM
Clinical Data Acquisition Standards Harmonization:
Basic Data Collection Fields for Case Report Forms
Prepared by the CDISC CDASH Core and Domain Teams
Revision History
Date Version Summary of Changes
2008-08-22 Final Draft 1.0 NA
CDASH Standards
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© CDISC 2013
Metadata Tables
Full question text for the
data collection
field. Either question text or prompt can
be used on the CRF
Short prompt for the data collection
field; could be used as
the CRF label
SDTM Variable Name
OR CDASH Variable Name
BRIDG
Mapping Defines the Data
collection field
Instructions for the
clinical site on how to enter data
on the CRF. Includes
controlled terminolog
y
Information/rationale and instructions on how to implement
the CRF data collection
fields
Designations
HR
Rec/Cond
Optional
© CDISC 2013
Overview of CDASH Tables
Domain tables contain most common fields in clinical trials
• Supplement therapeutic area-specific fields according to protocol
Standard domains do not contain everything
Domain tables are arranged in alphabetical order
• Data collection fields are presented in the domain tables similar to the order found on a CRF
• Example CRFs are in the CDASH UG
CRF layout is not part of scope
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Section 4.3 of CDASH v1.1
© CDISC 2013
General Notes
• Applies to both paper CRFs and eCRFs• If something only applies to one, it will be noted in
the standardCDASH
• What is on the CRF• Date concomitant medication was started“Fields”
• What is in the database• CMSTDAT, or CMSTDY, CMSTMO, CMSTYR,
etc.“Variables”
• Encompasses investigational products, devices, study drug, etc.“Study treatment”
Section 1.2.1 of CDASH v1.1
© CDISC 2013
Data collection mechanisms
CDASH is system-independent
When a CRF restricts responses to a set list of choices, different collection systems may handle it differently
• Tick box, Check box, Code list, Pick-list, Radio buttons, Dropdown list
These are all interchangeable ways to describe a pre-defined list of response choices on the CRF
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Section 1.2.1 of CDASH v1.1
© CDISC 2013
CDASH Standard Document Contents
• Header data elements presented first• CRF domains (topics) arranged alphabetically
Documents the defined standard for data collection, organized by CRF “topic”
Best Practices on CRF design along with FAQs
Provides references to regulatory documents that were considered during CDASH creation
Describes how CDASH relates to other CDISC standards
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Section 1.2 of CDASH v1.1
© CDISC 2013
CDASH User Guide
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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.
© CDISC 2013
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
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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
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© CDISC 2013
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)
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© CDISC 2013
CDASH Overview
Q&A
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