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?