1. _______________________________
DSBS
30th May 2006, Annual Meeting
_____________________________________
DMC – how and what should they evaluate?
_______________________________
Bjarne Nielsen, Vice President Biometrics

2. DMC – Data Monitoring Committees
General info
Medicon is involved in DMCs for several clients and have a special group dedicated to DMC tasks.
Medicon is involved either as a member of the DMC or as external statistician to perform statistical analysis for the DMC, keeping the client blinded for the trial.
Medicon is at the moment involved in 12 DMC worldwide.

3. DMC Group – staff at Medicon
Bjarne Nielsen, MSc Statistics
Vice President Biometrics
Martin Eeg, MSc Statistics
Senior Biostatistician
Peter Meisels, MSc Statistics
Senior Biostatistician
Allan Prang, MSc Biology
Senior Statistical Programmer
Tony Awwad, MSc Economy
Statistical Programmer
Rita Schou,
Executive Assistant
Jesper Nelby Kristiansen, MSc Biology
Senior Data Manager

4. DMC – Data Monitoring Committees
Typical Procedures
An Independent experienced DMC is selected and a Charter is produced with input from DMC and protocol input is made.
Open and closed sessions are prepared, a SAP is made showing deliverables (data packages) and timelines. A face-to-face meeting is held.
During the trial, telecons or web-conf are held. The DMC receives data packages typically 3-5 working days after Medicon receives interim data.
DMC requests additional or revised analyses or data presentations.

5. Typical Procedures, continued
DMC Data Handling
Typical Procedures, continued
Data sources: We receive data from various sources,
e.g. Laboratories, Safety departments, Event committees,
Study database, ECG readings, Fax forms.
Timelines: Typically, we deliver the data package 3-5 days after
receipt of (unclean) data.
Web site: MUDA – Medicon Upload & Download Area.
For easy exchange of information between DMC members.
Personal Username and Password required in order to
gain access to this site.

6. DMC – Data Monitoring Committees
What should the DMC do? – apart from recommending to either continue or stop the trial
Ensure patient safety, Ensure patient safety, Ensure patient safety.
Evaluate safety data and compare to control and/or expectations.
Evaluate whether the conduct of the trial and the data quality are sufficient to make recommendations and ensure that ”patients are not waisted” on inconclusive trials due to sloppyness.
Evaluate safety in relation to risk/benefit – requires often efficacy considerations, Ensure patient safety.

7. DMC – Data Monitoring Committees
What should the DMC do?
– Evaluate safety
Evaluate AEs and SAEs, critical events etc – often on a case-by-case basis.
Evaluate other safety data like ECGs, laboratory data or mortality.
Evaluate dose effects on the above mentioned data.
How should they do that?
Review data overview (descriptive summary tables and plots and stat.tests).
Review case data.
Use statistical stopping rules as guidance.
Look for expected as well as unexpected findings.
Look for trends, e.g across dose groups – even across trials!!

8. DMC – Data Monitoring Committees
What should the DMC do?
– Data quality and study procedures
Review data, missing data patterns and magnitude.
Review study procedure appropriateness, e.g. randomisation bias, bias in censoring or sloppyness on crucial data collection points.
Ensure comparabililty of data – issues relevant also in final reporting.

9. DMC – Data Monitoring Committees
What should the DMC do?
– Risk / benefit evaluation
Not sample size adjustment in order to reach efficacy conclusion.
Basis for evaluation of risk, taking the benefit into account – requires hard endpoint data on efficacy – which may only be partly available – e.g. long time mortality measures. Often an issue for discussion.

10. DMC – Data Monitoring Committees
Conclusion
A DMC must ensure patient safety
Meet and discuss up front
Find experienced members
Plan, but be prepared for changes

11. For further information on Medicon, please contact:
Contact Details
For further information on Medicon, please contact:
Bjarne Nielsen, MSc Statistics
Vice President, Biometrics
Medicon Biometrics
Datavej 24
P.O. Box 130
DK-3460 Birkerød
Denmark
Phone:
Fax: