CDASh : A Primer and Guide to Implementation

1. CDASh : A Primer and Guide to Implementation Mark Wheeldon NJ CDISC User Group Merck, Summit September 19, 2013

2. AGENDA • 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

3. Introduction • 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

4. INTRODUCTION TO CDASH

5. What is CDASH? What it is Not • 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

6. How CAN CDASH BE Stored? • 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

7. What is CDASH ODM? Clinical Context Submission Database Content and Structure Codelists Extended ODM Structure

8. CDISC Saves Time & Money • 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 buildbuild • 55% reductionin EDC build • Study Conduct and Analysis • 76% reduction in dataset production

9. Perfect Libraries with CDASH

10. CASE STUDY- CDASH not used 8 STUDIESIN SAME THERAPEUTIC AREA 342 MIXTURE OFEDC/CRO VENDORS FORMS 143 UNIQUEFORMS Multiple permutations of Forms present 10 MEDICAL HISTORY FORMS 5 SURGICAL HISTORY FORMS 15 VITAL SIGNS FORMS 6 PHYSICAL EXAM FORMS 36 FORMS WITHOUT CDASH 4 MASTER LIBRARY FORMSWITH CDASH = 36 FORMS

11. CRF Reuse Before & After • Use study 1 as a library • Add each ‘new' form from studyto study • Do not standardize • End-to-end reuse low until final studies WITHOUT CDASH WITH CDASH • Standardize common forms • 66 vs. 142 unique forms • 22 CDASH forms • End-to-end reuse high in early studies

12. Study specific demographics CDASH LIBRARY – MASter DEMOGRAPHICS EXAMPLE

13. CDISC Models and CDASH Content Perfect Reuse Everywhere. • 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

14. CDASH with multi-EDC vendors

15. CDASH Multi-Vendor eCRFs Autogenerated

16. Implementation Issues - cdash WITH multi-EDC vendors • 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.

17. Implementation Issues - SOLUTIONS • 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

18. Mapping CDASHto SDTM

19. Advantages of CDASH

20. Selection of CDISC Standard Domains Map to 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)

21. CDASH ODM CDASH & SDTM Alignment CDASH CRF Label Question SDTM Controlled Terminology SDTM Variable Name CDASH Core (Highly Recommended)

22. Optimizing Downstream Dataflows 1 1 2 2 3 3 4 4 5 5 6 6 Non-CDASH Form CDASH Form

23. Optimizing Downstream Dataflows Non-CDASH CDASH 1 5 4 6 2 3

24. Pure CDASH : Vertical Needs Help Sometimes • 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

25. CRF - SDTM DATA MAPPING Horizontal - vertical CRF COLLECTION DB SDTM DATASET COLLECTION DB USUBJID USUBJID TEMP VSTESTCD TEMP_U PULSE VSORRESU PULSE_U VSORRES TEMP. 38.0 1001 TEMP ° USUBJID TEMP TEMP_U PULSE PULSE_U C C C C C ° ° ° ° 1001 82 38.0 BPM BPM 82 1001 PULSE TEMPERATURE 1001 82 38.0 BPM PULSE 38.5 1002 TEMP 1002 79 38.5 BPM ° ° C C BPM BPM 79 1002 PULSE 1002 79 38.5 BPM PULSE

27. Conclusions • 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

28. ANY QUESTIONS?