1. Implementing metadata standards at the protocol level
CD12 - Implementing metadata standards at the protocol level
24 December 2018
Implementing metadata standards at the protocol level
Phuse Berlin
October 2010
Annabel Acs

2. CD12 - Implementing metadata standards at the protocol level
24 December 2018
I would like to begin my presentation with a little analogy. Maybe you remember this from your high school science class – this fire triangle- the idea behind it is quite simple – you just need the combination of air, fuel and heat to create fire, but without one of these key factors – you will not create fire…
Imagine the fire triangle – require three essential elements to create fire – air, heat and fuel.

3. Standard Technology Process
CD12 - Implementing metadata standards at the protocol level
24 December 2018
Standard
Technology
Process
Similar to the fire triangle – in order to implement standards, you need to establish 3 essential elements must be implemented, standards, technology, process. And without one of these factors – it will be difficult to successfully implement standards

4. The standards and technology at NN
CD12 - Implementing metadata standards at the protocol level
The standards and technology at NN
24 December 2018
Protocol Standards
CRF Standards
CRF
CRF
CRF
Submission Standard
Date:
/ /
Abc: x: y:
Qwr:
CDISC SDTM
Data Domain: PE
<XML> .…
CDISC ADaM
Data Domain: ADPE
<XML> .…
Standard DCM/DVGs
CDW
Numeric Findings
Categoric Findings
Subject
Events (AE/Hypo/x)
Interventions
Visits
Elements OC
Table
Responses
Std. EOT
XXCgfg hghj dklædfjkll sdfkf jklsd
Xxxx
Xxx
Xxxx
I will not spend too much time with this slide – I have included it makinly to give a big picture of the standards and systems we use at NN and how they are linked. We have standards within each area – protocol, CRF.. Etc. and we have worked to align with standards within the systems/areas. Howwever the main focus of this presentation is protocol metadata standards and how we have implemented metadata standards at the protocol level to support CDW and the standard terminology used in CRFs. At NN we have standards within the following areas – protocol standards, CRF standards, DCM/DVG standards – etc. We have systems to support these standards – protocol standards feed into CDW and CRFs – CRF standards feed into OC – standard DCMS.
CDW – Clinical Data Warehouse, supports generation of standard outputs and standard submissions. Since the standards created at the beginning a trial wil inevitably affect the standards used at the end – we have work to align the protocol standards with what is in CDW. The motivation for doing this is because the standards used in the protocol will impact those used in the CRF and continue through to data collection chain. Therefore it’s best to implement these standards at the protocol level. The focus of the presentation is HOW we’ve done this at NN.
We have worked to align standards across these areas.
Mapping
rules
Standard Reports
Standard Mappings
Standard Code Values

5. The process supporting standards and technology at NN
CD12 - Implementing metadata standards at the protocol level
24 December 2018
The process supporting standards and technology at NN
Trial
Management
Data
Management
Programmers
and
Statisticians
Process – about the people involved – trial manager are setting the standards on the protocol level – using the PMT, data management has used CRF/OC to set standards and programmers and stat have been in stat standards. In the past and currently with CDW – there is a relatively dialogue between DM and stat – both are focused on standards and aware of CDISC. More of a challenge to create and implement standards and develop more a of process between trial management and stat.
Can argue that the processes within stats have been refined around the new system. The processes between DM and stats have also been affected – primarily because OC set-up and mapping is essential for CDW to work. Furthermore DM is already focused on standardisation, particularly CDISC standards

6. PMT technology Protocol Metadata Template (Excel) Inexpensive
Easy to use
Easy to modify
Familiar to everyone
At NN – we have created an Excel based tool – Protocol Metadata Template – to align and support the standards used in CDW with those used in the protocol.
There are standard templates for Visit tructure, description of TD, TD diagram, TP, Dosage, TF – each template has a series of drop down menues from which standard terms can be selected. The structure of the templates and the terminology used is aligned with CDW – which in turn is very much aligned with CDISC terminology.
A little history: the origninal intention of CDW was that it could be used by TM as well to enter protocol metadata – this was descoped and consequently a tool with Excel was created instead. You could argue that it was actually a benefit to use Excel because it is easy to modify (we’ve had several updates) minimal training, already familiar to endusers. Furthermore, CDW is a complex system, which we are still upgrading and perfecting – therefore it
The downside of Excel is that it is not a validated system – cannot transfer the information directly from excel to CDW.
Set backs with using excel: not a verified system so you cannot directly transfer the data from excel to CDW – data must be manually re-entered into CDW.

7. Title – free text
Objectives – free text
End-points – free text
Visit structure – template – mix of drop down menus and free. Helps to ensure that visits are described consistently and always in relation to time point 0 – aids analysis at a later point.
Description of trial design – code lists to select from to describe trial
Trial design diagram – template
Trial products – template
Dosage - template
Trial flow chart – template
Sampling profile – template
Functionalities – Word document – verified and can be filed with the protocol. Update the codelist from a master file – constantly updated

8. Protocol Metadata Template standards
CD12 - Implementing metadata standards at the protocol level
24 December 2018
WBC
Leucocytes
White
Blood
Cells
Protocol Metadata Template standards
Code sheet in CDW which contains a list of terminolgy used in the PMT, which is aligned with CDW. With the prefered term, for example leucocytes, there is also a list of synonyms. In the past protocols were created with the investigated in mind and prefered terms were selected based on what’s appropriate for the investigator – now prefered terms are aligned with CDISC and it is possible to include a synonym if needed.
PMT standards group which maintains this list and evaluates requests for new standards – keeping in mind CRF, OC and CDw standaards. Somehow create a way for CDWs clinical and trial metadata to be used throughout protocols – this will influence which standards are used in the CRF – OC – CDW- Stat progs and analysis -> based on CDSIC terminology

9. Example of trial flow chart – they use drop menus to select the needed code.

10. Visit structure – drop down menus to describe visits – aligned with CDW. Ensures that visits are described in a common way throughout all protocols

11. The trial design diagram is aligned with CDW trial design and supports the development of generic trial designs. Primarily making it possible to quickly grasp the design of a trial, compare designs of different trials, seach within the data warehouse 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)
Add to sat programming

12. Trial Design defined in CDW-O with protocol attributes
CD12 - Implementing metadata standards at the protocol level
24 December 2018
Trial Design defined in CDW-O with protocol attributes
TD is entered into CDW which is a validated system and validated metadata source, which can then used for analysis in SAS DD
CDISC terminology carried through into

13. CDISC controlled terminology

16. The process supporting the standards and technology
CD12 - Implementing metadata standards at the protocol level
24 December 2018
The process supporting the standards and technology
Protocol
Draft
Protocol Metadata Template
1.0

17. The process supporting the standards and technology
CD12 - Implementing metadata standards at the protocol level
24 December 2018
The process supporting the standards and technology
Trial Mng
Data Mng
Programmers and Statisticians
Medical Writers
Time
New tool
Admin.

18. Improving the process…
CD12 - Implementing metadata standards at the protocol level
24 December 2018
Improving the process…
SOPs
Training
Mng Attn.
New
Processes
Trial Mng
Data Mng
Programmers and Statisticians
Medical Writers

19. Vision for future Clinical System Architecture
CD12 - Implementing metadata standards at the protocol level
24 December 2018
Vision for future Clinical System Architecture
Portal
Other eRecords
eRandom
Coding
CTMS
IWRS
EDC
LAB
Safety
SCE BI
cBI
PACT
eCTD
Dictionaries
Set Up
Conduct
Analyze
Publish
Training & Processes
Master Data
Metadata
Repository
Clinical
Source Data
Repository
Enriched Clinical
Data
Repository
Submission
Outputs
Repository
eStandard
eProtocol
eDCS
eSPS
ePSPS
Set-up
Verify
Enrich
Analyse
Process Data Repository