1. Standardisation of Trial Design Definitions in CDW at Novo Nordisk
Nordic CDISC User Group meeting
Copenhagen 22-April-2008
Mikkel Traun

2. Agenda 1 2 3 4 5 Trial Design in context of CDW at Novo Nordisk
Standardisation of Trial Design Definitions in CDW
Agenda
Trial Design in context of CDW at Novo Nordisk 1
CDISC SDTM Trial Design Model 2
Standardised Protocol Trial metadata 3
Trial Design metadata in CDW 4
SDTM submission dataset from CDW 5

3. Lets start with the Novo Nordisk R&D Vision
First with Superior Therapies
R&D Vision
To be recognised as world leaders in drug development
Key Goal
Reduce overall time to market
Support increased number of projects
Reduce late phase pipeline attrition
Value Drivers
Reduce
overall costs
Support
market launch
Support larger increase in patient volumes
Utilize resources more efficiently
Leverage data better
Critical Success
Factors
Introduce the vision of Global Development and the connesction to the Eclinical programme:
Create overview of link between business goals and our identified drivers and especially critical success factors (CSFs)
Achievement of the CSFs will beneficially impact on achieving the business goals
The eClinical vision:
To achieve global integration of business processes enabled by the optimal capture of data, integration of systems, and better use of data
For eClinical to support “F1rst with superior therapies”, it is necessary to focus on increasing the number of projects we can support, and reduce the overall time to market for our products.
- We will do this by working smarter, by increasing our flexibility
and by tying Global Development together across the world.
With eClinical, Global Development will, in 2008, be characterised by…
A global resource and portfolio management that will enable a flexible allocation and execution of development activities
A co-ordinated, more cost effective clinical supplies organisation
Information and systems available on a clinical data platform increasing flexibility for data usage and improving the work environment for global development staff worldwide
Quick access to historic data enabling better planning and execution everywhere across Global Development
Optimal data usage enabling adaptive development programmes and increased support of marketing and labelling activities as well as requests from authorities
Efficient global processes that support EDC and will result in a higher data quality and timely trial execution
Performance based investigator recruitment
eClinical

4. F1rst with superior therapies Shortened time to market
Standardisation of Trial Design Definitions in CDW
By building the Clinical Data Warehouse (CDW) we will help Global Development reach its vision
F1rst with superior therapies
Shortened time to market
Research
Product Launch
Clinical Data
Improved decision making based on better utilisation of our accumulated data and knowledge
Stream-lined processes and tools for statistical analysis and clinical interpretation
CDW

5. The CDW system is a means to reach the vision of Global Development and obtain the benefits
Foundation for the solution
Standardised global platform for statistical analysis and reporting
Establishing common standard clinical data model
Creation of trial design meta data standards
Cross-organisational clinical data warehouse
Frontloading and use of standards
Clinical Data and trial meta data model
Standard program catalogue
Access to historic clinical data for analyses
Adequate process changes
Development of a validated standard program catalogue for use in EOT documents
Standardisation
The Clinical Data Warehouse is an environment for Statistical Analysis and Reporting in Global Development and the CDCs
The “shelves in the warehouse will gradually be filled’ with clinical research data structured to support the research processes in Global Development and the CDCs
Allowing access to historic clinical data for explorative analyses

6. The benefits to be obtained with CDW
Standardisation of Trial Design Definitions in CDW
The benefits to be obtained with CDW
Compliance with federal regulations and NN procedures - globally 3
Increasing capacity of existing statistical staff 1
Ease the integration of data in clinical summaries and leveraged use of historic data 6
Reduction in critical time path for statistical analysis 2
Expansion of statistical knowledge and capabilities 4
Globalization and knowledge sharing of clinical data 5
2008
2009
2010
Editing: All objects are editable with PowerPoint. Adjust, copy and paste elements. Change the position of processes. Delete excess elements.

7. Agenda 1 2 3 4 5 Trial Design in context of CDW at Novo Nordisk
Standardisation of Trial Design Definitions in CDW
Agenda
Trial Design in context of CDW at Novo Nordisk 1
CDISC SDTM Trial Design Model 2
Standardised Protocol Trial metadata 3
Trial Design metadata in CDW 4
SDTM submission dataset from CDW 5

8. CDISC SDTM Trial Design Model
Standardisation of Trial Design Definitions in CDW
CDISC SDTM Trial Design Model
Purpose is to support reviewer to:
Clearly and quickly grasp the design of a clinical trial
Compare the designs of different trials
Search a data warehouse for clinical trials with certain features
Compare planned and actual treatments and visits for subjects in a clinical trial (future)

9. CDISC SDTM Trial Design datasets
Standardisation of Trial Design Definitions in CDW
CDISC SDTM Trial Design datasets
Trial Arms (Planned)
Trial Elements (Planned)
Trial Visits (Planned)
Trial Inclusion/Exclusion Criteria (Lookup table)
Trial Summary (Descriptive attributes of trial)

10. CDISC SDTM Trial Design Trial Elements, Arms, Visits
Standardisation of Trial Design Definitions in CDW
CDISC SDTM Trial Design Trial Elements, Arms, Visits

11. Agenda 1 2 3 4 5 Trial Design in context of CDW at Novo Nordisk
Standardisation of Trial Design Definitions in CDW
Agenda
Trial Design in context of CDW at Novo Nordisk 1
CDISC SDTM Trial Design Model 2
Standardised Protocol Trial metadata 3
Trial Design metadata in CDW 4
SDTM submission dataset from CDW 5

12. The CDW system - Standardisation is the foundation!
Standardisation of Trial Design Definitions in CDW
The CDW system - Standardisation is the foundation!
Cross-organisational clinical data warehouse
Clinical Data and trial meta data model
Standard program catalogue
Access to historic clinical data for analyses
Adequate process changes
Standardisation

13. Standardisation of Trial Design Definitions in CDW
The Clinical Data Warehouse affects the data analysis and reporting process
Initiate Trial
Set-up
Metadata
Transfer
Data
Conduct
Analysis
Prepare
submission
Request for Trial Definition and Trial Container
Use metadata standards from protocol onwards
Access request for Trial Definition and Trial Container
Metadata set-up is mandatory
Protocol and statistical metadata mainly entered through applications a few transferred from Source System
Mapping of transfer from OC to CDW
Data Enrich-ments in transfer from OC to CDW
Use of standard programs from standard library
Standardised framework for making derived datasets
Metadata ADM contains reference of the metadata for trials available in CDW to use for searches
Storage of data to facilitate SDTM data submission
We want to make this more real life by showing how a trial is processed with CDW. We will do this by covering these 5 key areas in the process
What are the 5 key areas dealing with? Slowly go through each area – and remember to say that we will look at the definition of a trial definition and a trial container later in the presentation.

14. Protocol information (metadata) to include in CDW
Standardisation of Trial Design Definitions in CDW
Protocol information (metadata) to include in CDW
Title – free text
Objectives – free text
End-points – free text
Visit structure – template
Description of trial design – code lists
Trial design diagram – template
Trial products – template
Dosage - template
Trial flow chart – template
Sampling profile - template

15. How to define and enter protocol metadata
Standardisation of Trial Design Definitions in CDW
How to define and enter protocol metadata
Templates have been created in Excel worksheets
Standard definitions and terminology has been agreed and code lists created
Standard terms are to be selected from drop down lists in the templates
Code lists will be updated on a regular basis when requested

16. How to define and enter protocol metadata
Standardisation of Trial Design Definitions in CDW
How to define and enter protocol metadata

17. How to define and enter protocol metadata
Standardisation of Trial Design Definitions in CDW
How to define and enter protocol metadata

18. Definition of Visit structure
Standardisation of Trial Design Definitions in CDW
Definition of Visit structure

19. Definition of Visit structure
Standardisation of Trial Design Definitions in CDW
Definition of Visit structure

20. Definition of Visit structure
Standardisation of Trial Design Definitions in CDW
Definition of Visit structure

21. Description of trial design
Standardisation of Trial Design Definitions in CDW
Description of trial design

22. Description of trial design
Standardisation of Trial Design Definitions in CDW
Description of trial design

23. Standardisation of Trial Design Definitions in CDW

24. Standardisation of Trial Design Definitions in CDW
Trial design diagram

25. Standardisation of Trial Design Definitions in CDW
Trial products

26. Standardisation of Trial Design Definitions in CDW
Trial products

27. Standardisation of Trial Design Definitions in CDW
Trial products

28. Standardisation of Trial Design Definitions in CDW
Dosage

29. How to use the templates
Standardisation of Trial Design Definitions in CDW
How to use the templates
When a new protocol is being created the templates must be used to secure that protocol metadata are defined in a standardised way.
After completion the excel worksheets, these are exported to a ’Protocol metadata document’
This ’Protocol metadata document’, are separate sheets that will follow the protocol and which will be filed in NovoDocs
The protocol originator may choose to include completed templates or part of these in the protocol text
Use of protocol standards will be included in the QC check of protocol before PRC submission

30. Agenda 1 2 3 4 5 Trial Design in context of CDW at Novo Nordisk
Standardisation of Trial Design Definitions in CDW
Agenda
Trial Design in context of CDW at Novo Nordisk 1
CDISC SDTM Trial Design Model 2
Standardised Protocol Trial metadata 3
Trial Design metadata in CDW 4
SDTM submission dataset from CDW 5

31. Create Generic Trial Design 1
Standardisation of Trial Design Definitions in CDW
Case 3:
Create Generic Trial Design 1
What is generic trial design
A template of a Trial Design, where the type and relationship between arms, branches, epochs and elements are defined.
The generic trial design template facilitate a standardised definition of trial design that supports the generation of trial design submission datasets and can be used by standard programs.
Terminology (arms, branches, epochs, elements)

32. Create Generic Trial Design 2
Standardisation of Trial Design Definitions in CDW
Case 3:
Create Generic Trial Design 2
Illustrating Element, Arm, Visit

33. Create Generic Trial Design 7
Standardisation of Trial Design Definitions in CDW
Case 3:
Create Generic Trial Design 7
Generic Trial Design as defined in CDW-Operations

34. Create Generic Trial Design 8
Standardisation of Trial Design Definitions in CDW
Case 3:
Create Generic Trial Design 8
Trial Design defined in CDW-O with protocol attributes

35. Trial Design datasets in CDW SCE Planned Trial Arm
Standardisation of Trial Design Definitions in CDW
Trial Design datasets in CDW SCE Planned Trial Arm

36. Trial Design datasets in CDW SCE Planned Trial Element
Standardisation of Trial Design Definitions in CDW
Trial Design datasets in CDW SCE Planned Trial Element

37. Trial Design datasets in CDW SCE Planned Trial Epoch
Standardisation of Trial Design Definitions in CDW
Trial Design datasets in CDW SCE Planned Trial Epoch

38. Trial Design datasets in CDW SCE Planned Trial Design Matrix Cell
Standardisation of Trial Design Definitions in CDW
Trial Design datasets in CDW SCE Planned Trial Design Matrix Cell

39. Agenda 1 2 3 4 5 Trial Design in context of CDW at Novo Nordisk
Standardisation of Trial Design Definitions in CDW
Agenda
Trial Design in context of CDW at Novo Nordisk 1
CDISC SDTM Trial Design Model 2
Standardised Protocol Trial metadata 3
Trial Design metadata in CDW 4
SDTM submission dataset from CDW 5

40. Data Flow Metadata driven data flow ADS DDM Source Systems
Standardisation of Trial Design Definitions in CDW
Data Flow
Source Systems
Data Processing
Analysis & Reporting
NN CDMS
Statistical Computing Environment
OC Clinical data
OC Metadata
MedDRA
Staging
ADS
IMPACT
DDM
Trial Metadata
Tables, Listings, Figures,
Submission datasets
Statistical Documentation
CDW Operations
CDR
ADM
Admin
MDR
SDM
MMA
Since we have a technical audience I actually dare to walk you through the dataflow. First we will focus on the Source systems. The first Source we have is familiar to all of us and that is data from OC, from OC we need to have the Clinical data (Visit structure, CDMS Treatment Pattern) and the MedDRA dictionary.
From IMPACT information about Site/Investigator is transferred into the metadata.
From the different applications various types of metadata is entered, we will go into details on that later in the presentation, where you will actually see some of the screens.
All the information (metadata is saved in the MDR (Meta Data Repository) and transformed and loaded into the staging area.
Using this meta data information the clinical data now is loaded into the Final CDR and the ADMs is created.
With the DDM load a framework is created to handle all the enrichments and creation of the DV, the statistical data handling decisions and some denormalisations.
If needed for specific purposes the ADS’s can be created, typically just a transformation of the data for use in a specific procedure.
In the new statistical computing environment you now can generate the statistical documentation using the standard programs and custom programs.
Metadata driven data flow

41. Standardisation of Trial Design Definitions in CDW
SDTM Trial Arm dataset

42. Query for SDTM Trial Arm dataset
Standardisation of Trial Design Definitions in CDW
Query for SDTM Trial Arm dataset

43. Standardisation of Trial Design Definitions in CDW
SDTM Trail Arm dataset

44. The trial meta data - brings us a number of benefits
Standardisation of Trial Design Definitions in CDW
The trial meta data - brings us a number of benefits
Data handling
Statistical Analysis
Reporting
In order to make use of the data in the CDW, the trial metadata need to be standardised
Metadata driven mapping and enrichment of study data
Matching analysis methods to study design
Metadata driven reports and output management
Today
Tomorrow with CDW
Data
Preparation
Reporting
Data Preparation
Reporting
Programming code reusability
Integration of data into standardised structure
Data preparation & reporting optimisation
Frontloading

45. …next Questions How do you plan to manage Trial Design metadata
Standardisation of Trial Design Definitions in CDW
…next
Questions
How do you plan to manage Trial Design metadata