1. EUROPA ~ WP4 Clinical research Executive Organisation ( CREO) Paris, September 2004

2. WP4 activities overview Objectives - To establish a EuroPa clinical research and trial organisation for conducting industry-independent and industry-sponsored studies : Clinical Research Executive Organisation (CREO) - To select and design a first research project by the end of the funded period Responsible partners: Toulouse, in collaboration with Lisbon, Marburg and all EuroPa partners

3. WP4 activities – Tasks to be accomplished - Meeting with all partners and centres willing to participate in clinical studies; - Establishment of an executive committee; - Definition of procedures to decide which studies will be performed; - Definition of work flows for designing protocols and electronic case report forms; - Adaptation of the general EuroPa databank to the specific needs of a research clinical trial (RCT); - Definition of monitoring procedures and services needed; - Establishment of a strategy for web-based patients and study centre recruitment; - Initiation of and providing a co-operation with a biometrics department; - Planning an investigator initiated study as an example of a RCT; - Applying for funding of this RCT

4. WP4 deliverables 1st meeting of the RCT specialist groupmonth 0 Organigram of the structuremonth 12 2 nd meeting of the RCT specialist groupmonth 18 Manual describing procedures(C.Sampaio)month 24 Study protocol of the first RCTmonth 30 3 rd meeting of the RCT specialist groupmonth 32 Electronic case report form for the first RCTmonth 36 Final reportmonth 36

5. WP4 milestones Identified RCTmonth 24 Designed RCTmonth 30 Prepared application for external fundingmonth 36

6. WP4 Accomplished deliverables (1) 1st meeting of the RCT specialist groupmonth 0 Frankfurt, January 31 2002 ~ start-up (plenary) meeting (contractors council) including all project members, definition of objectives and of first working procedures for WP4 Organigram of the structuremonth 12 - Recruitment of WP4 manager (December 2002) -CREO constitution (Toulouse - May 31, 2002; Barcelona -July 12, 2002; Lisbon - July 13-14, 2002; Frankfurt - July 25, 2002; Vienna – October 27, 2002; Miami - November 10, 2002; Frankfurt January 9, 2003 ) 2 nd meeting of the RCT specialist groupmonth 18 Barcelona – July 11, 2003

7. WP4 Accomplished deliverables (2) Manual describing procedures month 24 CREO procedures (Jan04); SOPs ongoing (C. Sampaio) Study protocol of the first RCT month 30 Aug03: Process for project call; Nov.03 : Call for project; Dec03 : Reception of 4 proposals; Jan04 : CREO meeting in Toulouse for projects selection process; Feb04 : Circulation of proposals among steering committee and conf calls ; Mar04 : study selection process (conf call + face/face meeting in Lisbon); July04 final draft of the selected protocol and conf call 3 rd meeting of the RCT specialist group month 32 May04 : final selection by SC (conf call) ;

8. CREO objectives(1) - To facilitate, conduct and manage clinical research project 1-Centres accreditation 2- Select project 3- protocol redaction 4- CRFs & others supports writing 5- Ethics & legal aspects 6- Budget plan & funding 7- implementation of the project - To organise and manage CREO resources - To guaranty transparent information and fair access to all EuroPa partners 8- data collection 9- monitoring 10- data entry 11- data management 12- data analysis 13- study report 14- publication

9. CREO Organisation Role and responsibilities 11 EuroPa partners Steering Committee Scientific advisory board Executive Board Executive team Study Steering Board

10. CENTRE ACCREDITATION EuroPa STEERING COMMITTEE SCIENTIFIC ADVISORY BOARD STUDY STEERING BOARD STUDY PREPARATION QUALITY CONTROL STUDY FOLLOW-UP DATA MANAGEMENT DATA ANALYSIS STUDY REPORT EXECUTIVE BOARD EXECUTIVE TEAM SUBCONTRACTORS 11 EuroPa PARTNERS

11. CREO Executive Board (1) Members O. Rascol, C. Sampaio, W. Oertel up to the end of the EU; Responsibilities To give final approval on CREO activities To supervise their implementation and progress. To call for research projects & activities, To assess the feasibility of scientific projects proposed by the scientific advisory board, To identify the needs of a project, To set up the budget To distribute the tasks for study conduction to internal facilities if available or to external subcontractors (like CROs for example) according to availability and expenses. To participate in communication and fundraising activities.

12. CREO Executive Board (2) Functioning Report to the steering committee Meeting on a monthly basis (telephone, face /face) Chair : bi-annual rotation – (W.Oertel Jan-Jun04; C.Sampaio Jun-Nov04) Decision making process : by consensus (common agreement of the 3 CREO members). In the absence of consensus, the decision is submitted to the steering committee final decision. Supported by a CREO Executive Team

13. CREO Executive Team (1) Members : Managers designated by the Executive Board (at least one designated representative of Toulouse, Lisbon and Marburg). Responsibilities To accredit centres based on accreditation policies (abandonned) To write EuroPa Standard Operation Procedures (SOP) for the 14 tasks (ongoing – C.Sampaio) To track studies budget To co-ordinate Study Teams after the approval by the CREO Scientific Advisory Board To propose appropriated resources to ensure that project activities are performed in line with prevision regarding timing and budget To co-ordinate overall research activities from protocol initial phases until publications, i.e. data management plan & organisation, data analysis plan & organisation, study report, compliance to publication policies

14. CREO Executive Team (2) Functioning Report to the CREO Executive Board at least once a month. Meeting on a weekly basis (face to face or via teleconferences) Communication : Day by day work will take place via E-mail or telephone at the individual location.

15. CREO Scientific Advisory Board (1) Members: 1 representative designated by each of the 11 EuroPa clinical partners (Austria: W. Poewe, Czech Republic: E Ruzika, France: O. Rascol, Germany: W. Oertel, Israel: R. Djaldetti, Italy: P. Barone, The Netherlands: N. Leenders, Portugal: C. Sampaio, Spain: E. Tolosa, Sweden: H. Widner, UK: A Lees ) Responsibilities To select projects proposed by EuroPa members To submit selected projects to the Executive board for feasibility assessment according to EuroPa SOPs To define priorities among selected projects To ensure that all members will have a fair opportunity to propose and to participate into research projects. To designate a Principal Investigator (PI) for each project To regularly update CREO activities to all partners

16. CREO Scientific Advisory Board (2) Functioning Reporting : steering committee Chair : rotating on annual basis – 2004: C. Sampaio Decision making process : voting system (each representative will have 1 vote) Meeting on a 6-month basis in association with another meeting to save resources.

17. CREO Study Steering Board (1) Members Investigators, study staff (ie statistician, monitors,...) and will be Specifically appointed for each project Responsibilities To design and to write the protocol To design and to write appropriate study guidelines before anything is starting To select participating centres and to set up a study scientific committee To define centre commitments To track study budget To co-ordinate various scientific and logistic aspects (printing, sending, meetings,…) within the agreed budget together with the CREO Executive Team. To track patients recruitment. To ensure that all different CREO teams and boards are kept informed of any factors which might impact the project and the budget To propose a publication plan in relation with the project To write at least 1 study publication To update CREO Executive Team every month on project advancement status to all partners

18. CREO Study Steering Board (2) Functioning Reporting : executive board/ executive team/ study scientific committee Chair : principal investigator Decision making process : Principal investigator with the approval of the executive board/executive team/ study scientific committee Meeting on a weekly basis

19. First EuroPa project CROSS SECTIONNAL STUDY OF CHRONIC PAIN AMONG AMBULATORY PARKINSONIAN PATIENTS LIVING IN 11 EUROPEAN COUNTRIES Cross-sectional epidemiological type with full service -light logistic - low costs - rapid results

20. Hypothesis - The prevalence of chronic pain in PD is high, up to 50%, according to the last published survey in 1986 ; - Chronic pain could be associated with some markers of PD (severity, Dopa responsive or Dopa resistant symptoms, anxiety, depression, insomnia); - Chronic pain in PD has a significant impact on quality of life;

21. Objectives To evaluate the prevalence of chronic pain among ambulatory Parkinsonian patients living in various countries of Europe; To describe and compare the profile of Parkinsonian patients whether they feel pain or not; To evaluate the repercussion of chronic pain on the quality of life of the Parkinsonian patients.

22. Patients 600 ambulatory PD patients to be included ~ 50 first patients seen at each centre

23. OUTCOME CRITERIAS Principal outcome - Specific questionnaires about chronic pain in Parkinsons disease (in preparation – To be discussed) Secondary outcomes - To assess PD severity (Hoehn and Yahr, UPDRS, Schwab and England) - To assess chronic pain [visual analogic scale, short version of the Mc Gill pain questionnaire (if validated translation are avalaible)] - To assess quality of life (PDQ39, SF36)

24. ESTIMATED BUDGET Investigators/ centres (1 day doctor/centre/week) : 50 000 Material (CRFs, etc...) 15 000 Translation costs20 000 Study implementation (meetings)25 000 Monitoring60 000 Project coordination25 000 Data management & analysis50 000 Publication & Communication 5 000 TOTAL 250 000

25. TIME TABLE Project inception and preparation 9 months Project implementation and data collection 9 months Data analysis and publication 6 months