CDASH : A PRIMER AND GUIDE TO IMPLEMENTATION
Mark WheeldonNJ CDISC User GroupMerck, SummitSeptember 19, 2013
• Introduction
• What is CDASH? What it is not
• Perfect libraries with CDASH
• CDASH with multi-EDC vendors
• CDASH aids mapping to SDTM
• Practical CDASH mapping examples
• Conclusions
AGENDA
• Vendor neutral using CDISC since 2000 • Save time & money in End-to-End Clinical Trial• Universal Design with Formedix Origin™
• Data Acquisition Design & Dataset Design • Origin Study and Submission Modeller™
• Universal Execution with Formedix Transform™• Data Acquisition – Paper, EDC, ePRO & IVRS• Conversion – ETL• Submission – Annotated CRF and Define.pdf
• Create once work with all. Train in one work in all• Formedix Consult™ Consultancy Services
• Planning, preparation, implementation, multi-EDC execution• Won 2 CDISC awards – wrote much of ODM/define
INTRODUCTION
INTRODUCTION TO CDASH
• Content Standard NOT a Model • Covers 22 core Case Report Forms (CRFs)
Variable Names, Definition, Question Text
Instructions to the Site, SDTM Variable Mapping
• Core Designations is a killer feature Give clinical context on why something is collected Highly recommended, recommended/conditional, optional Clinical Perspective on data collection
•What it is not One-to-one mapping with the SDTM AEYN not in SDTM, AEBODSYS not in CDASH
WHAT IS CDASH? WHAT IT IS NOT
• Excel, Word, PDF Libraries Excel for database metadata Word for CRF mock-ups
• Global proprietary EDC Library Rave, DataLabs, Prism… Has shortcomings
◦ Lack of full support for CDISC◦ No alias support – automate aCRFs◦ No discrete measurement units support◦ Poor support for vertical structures
• Optimal solution CDASH in CDISC-ODM
HOW CAN CDASH BE STORED?
WHAT IS CDASH ODM?
Submission
Codelists
Extended ODM Structure
Database Contentand Structure
Clinical Context
• Libraries – Content Reuse 70% reuse Standards maintenance resources down by 23% Just this use case ROI – 8 months
• Study Set-up Specification auto-generation Boston Scientific proved a 68% reduction With CROs, Partners, EDC vendors ….
• Study Build Automate EDC build build 55% reduction in EDC build
• Study Conduct and Analysis 76% reduction in dataset production
CDISC SAVES TIME & MONEY
PERFECT LIBRARIES WITH CDASH
CASE STUDY - CDASH NOT USED
8STUDIESIN SAME
THERAPEUTIC AREA
MIXTURE OFEDC/CROVENDORS
342FORMS
143UNIQUEFORMS
Multiple permutations of Forms present
= 36 FORMS
10MEDICALHISTORYFORMS
5SURGICALHISTORYFORMS
15VITALSIGNSFORMS
6PHYSICAL
EXAMFORMS
36FORMS
WITHOUT CDASH
4MASTER LIBRARY
FORMS WITH CDASH
• Use study 1 as a library• Add each ‘new' form from study
to study• Do not standardize• End-to-end reuse low until final studies
CRF REUSE BEFORE & AFTER
• Standardize common forms• 66 vs. 142 unique forms• 22 CDASH forms• End-to-end reuse high in early studies
STUDY % REUSE
1 0
2 36
3 52
4 71
5 80
6 90
STUDY % REUSE
1 48
2 70
3 94
4 80
5 86
6 100
WITHOUT CDASH WITH CDASH
1 2 3 4 5 60
20
40
60
80
100
120
Percentage Reuse % Reuse%Reuse CDASH
CDASH LIBRARY – MASTER DEMOGRAPHICS EXAMPLESTUDY SPECIFIC DEMOGRAPHICS
•Quality is built in up-front not tested in•CDISC Libraries with CDASH Content
Clinical context – quicker clinician approval Vendor neutral and portable
•Design once Everything pre-approved so review reduced Only test new content or changed content Standardized CRFs = consistent data collection Standardized CRFs = standardized datasets/mappings
•Reuse of all study design components Across end-to-end clinical trial Across multiple vendors & data capture systems
CDISC MODELS AND CDASH CONTENTPERFECT REUSE EVERYWHERE.
CDASH WITH MULTI-EDC VENDORS
Drag picture to placeholder or click icon to add
CDASH MULTI-VENDOR eCRFS AUTOGENERATED
• Structural Issues CDASH vertical vs. EDC horizontal EDC systems allow only one vertical structure
• Poor/Lack of support for CDISC identifiers - lengths, character restrictions etc. Aliases – used to annotate/map to SDTM, Legacy fields ... Multiple languages Enumerated codelists
• Worst case ‘Hard coded’ CRFs required for EDC Demographics, Labs,
AE etc.
IMPLEMENTATION ISSUES - CDASH WITH MULTI-EDC VENDORS
• Structural Implement one field per question (horizontal) Implement vertical versions Split repeating sections on separate forms (incl/excl)
• Core Libraries Covers most use cases Special case specific EDC eCRFs in separate library
• Global aliases Company corporate identifiers used end-to-end everywhere Still supports EDC identifier restrictions
• Code / decode instead of enumerated codelist
IMPLEMENTATION ISSUES - SOLUTIONS
MAPPING CDASHTO SDTM
ADVANTAGES OF CDASH
• Interventions CM (Concomitant
Medications) EX (Exposure) SU (Substance Use)
• Events AE (Adverse Events) DS (Disposition) MH (Medical History)
• Findings EG (ECG) IE (Inclusion / Exclusion
Exceptions) LB (Laboratory Test Results) PE (Physical Examination) QS (Questionnaires) SC (Subject Characteristics) VS (Vital Signs)
• Special Purpose DM (Demographics) CO (Comments)
SELECTION OF CDISC STANDARD DOMAINS MAP TO CDASH
CDASH ODM CDASH & SDTM ALIGNMENT
CDASH CRF Label Question SDTM Controlled
Terminology
SDTM Variable Name
CDASH Core (Highly Recommended)
OPTIMIZING DOWNSTREAM DATAFLOWS
1
6
4
5
2
3
1
2
3
4
5
6
CDASH Form Non-CDASH Form
Drag picture to placeholder or click icon to add
OPTIMIZING DOWNSTREAM DATAFLOWS
1
2
3
45
6
CDASH Non-CDASH
• Vital signs (VS form)• Vertical implementation suggested• Optimized for dataset production
and not all easy to enter data.• Must repeat on VSTEST.
Cannot have repeat on time as well Form repeats for time points
• Other issues Every variable collected at every time
point even if likely to remain constant VSORRESU Units must be a pull down Error prone needs more edit checks Repeated collection of irrelevant values
• Pros: Simple dataset mapping
PURE CDASH : VERTICAL NEEDS HELP SOMETIMES
COLLECTION DB
USUBJID TEMP TEMP_U PULSE PULSE_U
1001 38.0 °C 82 BPM
1002 38.5 °C 79 BPM
CRF - SDTM DATA MAPPINGHORIZONTAL - VERTICAL
CRF
TEMPERATURE
°C
TEMP.
BPM
PULSE
PULSE
USUBJID TEMP TEMP_U PULSE PULSE_U
1001 38.0 °C 82 BPM
1002 38.5 °C 79 BPM
COLLECTION DB
USUBJID VSTESTCD VSORRESU
1001 TEMP
BPM1001 PULSE
VSORRES
°C38.0
82
1002 TEMP
BPM1002 PULSE
°C38.5
79
SDTM DATASET
•CDASH ODM is best format to store CDASH Union of all standards SDTM, ODM, CT EDC extensions and best practices
•CDASH saves time and money Clinical perspective Promotes reuse of CRFs and end-to-end designs Alignment with SDTM and mapping ease
•Compromises have to be made Multi-vendor and your own content No two CDASH libraries are identical
CONCLUSIONS
ANY QUESTIONS?