1) The document discusses the importance of standards for clinical research data and metadata exchange. It notes that electronic data capture (EDC) systems can increase efficiency and quality but require computer system validation. 2) A survey of German research networks found that over 80% saw exchanging metadata and clinical data as very or important. The top study partners for sharing data were universities, networks, and study groups. 3) Proper computer system validation is important for conducting GCP-compliant clinical studies. It ensures systems meet requirements through qualification and testing of components, computerized systems, and processes.

1. Evaluation of the importance of standards
for data and metadata exchange for clinical
research
TELEMED 2005
9.4.2005 in Berlin
W. Kuchinke, KKS Düsseldorf
R. Gernemann, KKS Charité
S. Wiegelmann, KKS Köln

2. Why Electronic Data Capture (EDC) in
Clinical Research
●
Reduced time spent on building and
managing studies for single center or
multicenter studies
●
eCRF form builder is user-friendly
●
Advanced user management and
workflow streamlines the data capture for
all your clinical trials

3. Functions of Electronic Data Capture
in Clinical Research
●
Ensure high-quality, clean data capture
●
Easily capture repeating measurement like
– Medical history
– Concomitant medications
– Unscheduled visits
– Adverse events
●
Capture data on multiple devices
– Desktop PC, Mobile phone, Tablet
●
Review the study subject‘s progress
●
Raise and manage queries throughout the entire study

4. Aim of the EDC project
• Create Process descriptions, as well as necessary
documents and checklists for any GCP-compliant
system validation (Computer System Validation, CSV)
• Provide output to all research associations of the
TMF (Telematics Platform for Medical Research
Networks)
• Research networks should be made aware of the
necessity and importance of using EDC systems and
conducting a corresponding computer system validation
•

5. Topics to consider
• XML-based data exchange can support cooperation in
scientific research networks
• Clinical data acquisition and study execution
• patient examinations
• electronic data (ECG, ...)
• laboratory data
• X-rays
• Formats of the data are different
• The way documentation in clinical trials is conducted differs
§ Restrictions exists due to the software used

6. EDC (Electronic Data Capture)
• Definition: Electronic recording of patient data in clinical
studies
• Internet use
• Increased efficiency
• Improved quality

7. XML for exchange of data
• New possibilities for integrating data and metadata
• New possibilities for standardization
• Automation of processes
§ Improving cooperation

8. CDISC, the standard for clinical
research
• CDISC Consortium (Clinical Data Interchange Standards
Consortium)
• Standard for the collection, exchange, submission to
authorities and archiving of data from clinical studies
• CDISC is global, vendor neutral, platform and software
independent
• XML-based standard for study content and metadata
• Examples: ODM (Operational Data Model), SDS (Submission
Domain Standard) and LAB (Laboratory Data Standard)
• Broad support and approval in the pharmaceutical industry,
but still largely unknown in the academic world

9. ODM Standard
• Completely XML-based
• Maps the entire clinical study
• Main modules:
• Study metadata
• Administrative data
• Reference data
§ Clinical data

10. Main and sub modules in ODM

11. Harmonization efforts effecting
clinical trials data
• Consolidation of data acquisition on the supply and research
level through harmonized XML standards
• HL7: leading standard for electronic exchange of supply data
• HL7 supports XML as a technology standard from V3
Reference Information Models (RIM)
• ICH Electronic Common Technical Document (eCTD)
• Technical Committee for HL7 Regulated Clinical Research
and Information Management (TC:RCRIM)
• Representatives of HL7 / Pharma, FDA and CDISC
• Harmonization of standard development between research
and supply

12. Infrastructure
Topology of project
collaboration
Coordination Centres
of Clinical Trials
Medical research
networks
Cooperation
EDC
Additional co-
operation partners

13. Germany
•
Information technology networking in the health care
system in Germany
•
Merging of the xDT standard for general practitioners with
the HL7 standard in the hospital sector
•
SCIPHOX

14. Telematics Plattform (TMF)
• Adresses the overarching problems of networked working
• Merger of research associations
• Competence networks in medicine
• Coordination centers for clinical studies
• National Genome Research Network
• Networks for rare diseases
• Further medical research collaborations
• Growing importance of standards for data and metadata
exchange

15. Survey among the network members
• Respondees: 42 associations of the TMF
• Standardized questionnaire
• 32 questionnaires were completed
• 11 questions on the exchange of clinical data and the
importance of standards
• Answered by senior IT or data managers of the networks
§ 5-value answer scale, ranging from "very important (=
1)" to "useless (= 5)

16. Survey questions
• Type of data and metadata exchanged by the TMF
consortia members
• Type of study partners mainly involved in data exchange
• Importance of the CDISC standards (ODM, SDTM, LAB)
for the networks
§ Degree of implementation of CDISC in the clinical study
software solutions in use

17. Survey among software companies
• Seven questions on the degree of implementation of CDISC
in clinical trial software solutions
• Answers range from "fully implemented" to "neither
implemented nor planned
• Existence of a strategy for the use of standards by developers
• Example companies that participated and their EDC software
solutions: eReseach Network from eReseach Technology,
MACRO from InferMed, secuTrial from iAS, PhOSCo from
Guillemot Design, CAP from CAP-Net

18. Example: Question about
importance of CDISC ODM
standard

19. Example: Question about
importance of data sharing

20. Results of survey
• 90% possibility of data exchange very important / important
• 80% Exchange of metadata very important / important
• Partners for data exchange
• universities = 91%
• Partners within the respective network = 81%
• study group = 78%
• Competency networks and PPS = 78%
• Exchange of laboratory data = 88%
• Patient data = 78%.
Requirements for data exchange
% Antworten mit „sehr wichtig
oder wichtig“

21. Computer Systems and
Validation
•
Computerized systems, includes all instrumentation and
software used to create, modify, transmit, or archive
data associated with work subject to federal
regulations (GCP, GLP, and GMP)
•
Addressed by Computer System Validation
•
Validation brings standard computerized systems into
regulatory compliance

22. Traceability Matrix
• Most important document for Computer System
Validation (CSV)
• Based on user requirements
• Based on the process of clinical studies
• Considers the GCP Impact (high, medium, low)

23. Importance of System Validation
• Improve the quality of clinical studies in a university
environment
• Able to conduct GCP-compliant studies and/or studies
relevant to market authorization
• Consider GCP and quality assurance
• Employ EDC software (MACRO, eResNet, CAP
network, PhOSCo, secuTrial)

24. IQ
Example of CSV test document: the test script for the Logon into the data entry
screen (IQ=Installation qualification)

25. OQ
Example of CSV test document for the Data entry into the EDC system
(OQ=Operational qualification)

26. OQ
Example of CSV test document: the Operation Qualification Plan for an EDC
system (OQ=Operational qualification)

27. OQ
Example of CSV test document: the test script for the Logon into the data
management system (OQ=Operational qualification)

28. Definitions
Open System
System access is not controlled
by the persons responsible for
the electronic records in the
system
Closed System
System access is controlled by
the persons responsible for the
electronic records in the system

29. 21CFR Part11
●
21 CFR Part 11 Electronic Records, Electronic Signatures
●
Validation of systems to ensure accuracy, reliability,
consistent intended performance, and the ability to discern
invalid or altered records. Protection of records to enable
their accurate and ready retrieval
●
Use of appropriate controls over systems documentation
●
Audit trail
– Use of secure, computer-generated, time-stamped audit
trails to independently record the date and time of
operator entries and actions
●
Limiting system access to authorized individuals
●
Use of authority checks to ensure that only authorized
individuals can use the system

30. Training
•
Third CSVHC-Konferenz über Software-Validierung für
das Gesundheitswesen (SQS) in Köln
•
Workshop Computervalidierung (Kendle)
•
PTS-Workshop 6.5.03

31. Working packages
•
KKS Düsseldorf (Tracebilitymatrix, Validation Master Plan,
Validation Plan, SOPs)
•
KKS Mainz/KKS Heidelberg (Evaluation of legal foundations
and guidelines, Glossary)
•
KKS Leipzig (security infrastructure, security SOPs, security
plan, security policy, risk analysis)
•
KKS Tübingen (test study and test cases, test plan, test
evaluation)
•
KKS Marburg (management)

32. Contact
Wolfgang Kuchinke, KKS Düsseldorf, University
Düsseldorf
●
wolfgang.kuchinke@uni-duesseldorf.de
The presentation was held at Telemed 2005 in
German.
The motto "bit for bit - halfway point on the way to the
telematics infrastructure" was the theme of the
TELEMED congress on April 8th and 9th in Berlin.