1. Cecilie Moe Oslo University Hospital
Clinical trial data management: Points to consider and the impact on the outcome
Cecilie Moe
Oslo University Hospital

2. Dept. of Research Support and the CTU
Comparative medicine
Henrik Rasmussen
3 sections, RAD, UL, RH
Research Admin and Biobanking
Peder Utne
2 teams (Biobanking and External funding)
Clinical Trial Unit
Jon B Borgaard
Section
monitoring
Elin Westerheim
10 staff
Section data management
Cecilie Moe
7(9) staff
Section HE, coordination and PROM (PROMiNET)
Ellen Johnsen
9 staff
GCP/QMS/QA
Martha Colban
Statistics, collab OCBE, workflow
Inge Christoffer Olsen
OCBE
Arnoldo Frigessi
OCBE OUS
Morten W Fagerland
Health Registry Support
Dominic Hoff

3. Data management process

4. Points to consider for CDM
Who/what regulates the data management
Qualifications and training
SOPs for clinical data management
Approved and validated computer systems
ALCOA+ standards
eCRF fit for purpose
Validation of data
Continues documentation of the DM process
Risk based approch to DM and central monitoring
Cross-functional teamwork and dvlp. of DM units

5. Who/what regulates the data management
Laws and regulations
National laws for research incl. GCP, personal data etc
Hospital procedures
How to implement privacy (the right to discontinue a study etc) and Information security (data systems) requirements
Guidelines
e.g. ICH documents

6. The skillset of a Data Manager includes:
Knowledge of best practices of study set-up and management of a living database
Database structure conventions (CDISC)
Medical coding (MedDRA, ATC)
Programming and logic
Statistics and study design
Project management
Continuing education in the computer systems incl. eCRF
Data Managers must work collaboratively and across many disciplines to make sure data is collected, managed and reported clearly, accurately and securely.

7. Qualifications and training
Heterogeneous group, different background
Be qualified and trained to do each task
Job descriptions
Regularly managing training requirements
training and development for individual DM
Documentation of training
Maintanance of training records
Up to data CVs
Educational background and training courses attended
Signed and dated

8. SOPs for clinical data management
Keywords: Version control, structured, revision, training and WI

9. Approved and validated computer systems
GCP 5.5.3:When using electronic trial data handling and/or remote electronic trial data systems, the sponsor should:
Ensure and document that the electronic data processing system(s) conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistent intended performance (i.e., validation).
ADDENDUM The sponsor should base their approach to validation of such systems on a risk assessment that takes into consideration the intended use of the system and the potential of the system to affect human subject protection and reliability of trial results

10. Data systems and data protection Some issues
How to protect the data?
Use of the right eSYS, PROM (Ipads in clinic, system to avoid capturing identifiable information)
Can’t afford Rolls Royce
GCP requirements: audit trail, back-up, certified copy, validation..
Storage of electronic and paper data (many hospitals lack archiving facilities) in a secure place
Distribution of electronic data
Secure login to eSYS, the hospital requires 2 factor auth
Requirements for sharing of data
For low budget studies, many researchers are their own data managers without training
Access to the best systems (EDCS, data validation systems, web browser, etc.)
Tender procedures required
The hospitals focus a lot on security, but not on GCP
Many prioritize personnel (study nurses, PhD) instead of costs for DM
Lack of focus on grant applications
Lack of understanding the need for DM and quality in each step

11. ALCOA+ standards
+ (CCEA) : Complete, Consistent, Enduring and Available
Can also be mapped to FDA Guidance for Industry: Electronic Source Data in Clinical Investigations which states that,
“Source data should be attributable, legible, contemporaneous, original, and accurate (ALCOA)”.

12. eCRF (pCRF) should be fit for purpose
Only collect the data needed
Use friendly eCRF
Data that could identify a subject
Database specification
Testing, testing, testing
Who should test?
Cross-functional team work

13. Validation of data What to check and how Data validation plan
Manual checks
Electronic checks
Query management
Audit trail of queries and changes
Database changes
Amendments etc
Protocol deviations
Maintain the blinding !!!

14. Documentation of the DM process
Written, reviewed and approved
Qualified persons to perform the tasks
Signed and dated with version control
Data management plan , what you plan to do
Data management report, what you did
Retain the documentation
Identify the owner

15. RBM (Risk based approch to monitoring incl
RBM (Risk based approch to monitoring incl. CDM) Responsibility of the sponor

16. RBM

17. Central monitoring
Centralized monitoring refers to the analysis of Critical to Quality (CTQ) data against quality targets and the communication of risk signals to orient clinical operations and data management activities, including monitoring visits, source data review (SDR), medical review, and risk mitigative actions.
Centralized monitoring implies ongoing collection and analysis of the information from the electronic CRF.

18. Risk classification

19. Monitoring activities

20. NorCRIN WP8: Data management
The main objective is to develop data management units at all partners’ local research support units with competent data management staff, as well as the required quality systems adapted to the local data capture systems.
A second objective is the focus on data management as an important part of the interdisciplinary team work facilitating the conduct of clinical studies.

21. ECRIN data center cerification
A not-for-profit organisation that supports multinational clinical trials
The European Clinical Research Infrastructure Network (ECRIN) is a not-for-profit intergovernmental organisation that supports the conduct of multinational clinical trials in Europe. As of 2013, ECRIN has the legal status of a European Research Infrastructure Consortium (ERIC). 
Based in Paris, ECRIN works with European Correspondents across Europe, national networks of clinical trial units (CTUs), as well as numerous European and international stakeholders involved in clinical research.

22. 16 units since 2011, 10 units are certified
The ECRIN Data Centre Certification programme identifies non-commercial clinical trial units (CTUs) in Europe demonstrating that they can provide safe, secure, compliant and efficient management of clinical research data.
The programme tests units for compliance with published ECRIN data standards through on-site audits of units' data management activities and the information technology (IT) infrastructure used to support these activities. ECRIN strongly recommends the use of certified data centres for the multinational trials it supports.
16 units since 2011, 10 units are certified
2 units in 2018, not report yet

23. ECRIN certification standards v3.1
Ny ver. 4.0 frigitt :

24. The impact on the outcome

25. Discussion/Questions
Cross-functional testing of eCRF
When?
How much?
Shared? responisbilities
Checking of data with overlapping areas, who is doing what?
Give monitors more access to data?