1 Research & Development Process Target Identification & Prioritization Drug Discovery Pre-Clinical Clinical Development Governance & Risk Management Regulatory Affairs (incl. FDA, SOX and SPL) Manufacturing Scale-up Portfolio and Project Management (incl. Budgeting Process) Presentation Focus Marketing

Today's Challenges in Managing Clinical Trials Horst Nowak Director Data Management & Biostatistics Omega Mediation – Clinical Research Services Bingen/Offenbach/Athens Digital Pharma: Effiziente Forschungs- und Entwicklungsprozesse in der Pharma-/Life Science-Industrie Wiesbaden, November 24, 2005

3 Definitions Clinical Trial Management (CTM) management data (e.g. times, resources, responsibilities, budget), trial meta data (e.g. from protocol, CRF, standards) Clinical Data Management (CDM) patient data (e.g. from CRF, diaries, electronic devices) Tools e.g. dictionaries, codelists

4 Requirements Clinical Trial Management (CTM) - project management on study and project level - status reports (availability and distribution of docs, trial progress) - key performance indices (benchmarks) - forecasts for other studies/projects - link to document management system (scanning, imaging) Clinical Data Management (CDM) - exchange (CROs, license partners, authorities) - establishment of a clean database, incl. validation/query process - availability of valid data for analysis and report - long term availability of data (audits, inspections) - link to document management system (scanning, imaging)

5 CDM: Sources for data past future paper data tables paper CRF paper diaries CRF: process oriented electronic diaries electronic CRF (PC based) electronic CRF (internet) electronic file transfer electronic data uploading patients investigators labs, devices

6 CDM: Interactions (data flow) Investigator Data Manager Monitor Patient DCF (Data Clarification Form) CRF diary Regulator Biostatistician Med. Writer lab, devices other Authority Reviewer Drug Safety SAE form

7 CDM: Cooperations Sponsor lab, devices Authorities CRO License partner(s) Investigators Patients electronically via paper

8 CDM and Clinical Operations (COp): new processes the past - CDM linear to COp: CDM to COp, COp to investigators - CRF development, database design prior to data entry the future - no need for paper exchange by COp at investigators - need for hot line and technical support - CRF = screen design as part of database design, prior to investigators' training

9 Challenges: CTM hierarchical data condensing real time information (automatic data exchange with CDM) distributed responsibilities: CROs for data delivery multisite access (user roles and rights) tracking of times and budgets focus on key performance indices workflow for defined events portability? validation?

10 Challenges: CDM (1) flexibility for different input data streams linkage to imaged documents (if paper is used) real time information (automatic data exchange with investigators and labs, e.g. internet) feedback actions, incl. correction request to investigators paper copies (for SDV, for long term documentation) data lock on various levels multisite access (user roles and rights)

11 Challenges: CDM (2) (status) reports in paper and as data exchange to CTM focus on key performance indices workflow for defined events portability (CDISC)! validation!

12 Case Study – Microsoft Merck

13 Improved Trial Administration Business value Hierarchical overview on all trial related information Real-time information Distributed roles and responsibilities for faster results Direct access to all critical information (costs, enrollement, etc.) Central administration of role access and security Direct links to team members Dashboard allows overview on trial status at-a-glance

14 Improved Trial Administration Business Value Fast, cost effective training via the participants’ laptops Training contents can be modularized to allow faster completion Improved user acceptance Consistent training of all study team members ensures conformity in study conduct Improved feedback on training needs and performance Certification and compliance Interactive Training modules Training can be run real-time or archived for self study

15 Standardized Data Collection Processes Business Value Reduced error rate and high acceptance by guiding users through data entry Templates based on standards including all FDA relevant fields Faster CRF generation by distributed authoring process Highly intuitive design using graphical elements CRF pages can only modified by authorized users

16 More Effective Data Management Business Value Real time tracking of patients during the study avoids over- recruitment Reduced error rates and rapid closure of queries Rapid freezing of patient data Real tiome status of all patients in the study Fast overview on study progress from different perspectives

17 Integration: CTM & CDM CTM CDM company IT environment

18 Conclusions and Critics Establishing modern CTM&CDM needs not only IT decision, but a re-organisation of many processes (across departments). Modern CTM&CDM solutions will speed up the availability of information for decision. It is in question how far this improvement will also speed up the entire development as there are many externally driven process steps. Shortening the number of trials is more efficient than looking into each trial into details. Independently from theoretically possible solutions, it must be decided whether an entire electronic solution is desirable. A paper backbone may be favourable with respect to FDA "21 CFR part 11" requirements. Full electronic solutions in the long-term development of drugs impose the problem of system and release changes.

19 Many thanks for your attention! Questions to: Dr. Horst Nowak Director, Data Management & Biostatistics Omega Mediation Clinical Research Services GmbH & Co. KG Kaiserleistr Offenbach am Main Tel.: Fax: Ruediger Dorn Director Process Manufacturing Industries Europe Middle East & Africa Microsoft Deutschland GmbH Tel. +49 (0) Fax +49 (0) Cell +49 (0) Mail