1. The database network taking it to the next level..... Bodo Grimbacher, MD University of Freiburg, Germany Head of ESID patient registries

2. Registry The existing ESID Registry Up-to-date patient- and research-databases The ESID Main Patient Registry The CVID Subregistry Requirements Time schedule Support for the documenting centers Summary Prospectives

3. a non-profit organization established in 1983, became a society in 1994 to facilitate the exchange of ideas and information among doctors, nurses, biomedical studies, patients and their families, collaboration with IPOPI and INGID to establish common diagnostic criteria (together with PAGID) (Clin. Immunol. 1999; 93:190). to promote research on causes, mechanisms and treatment - summer schools (education, pathogenesis, treatment of primary immunodeficiencies) - biennual scientific meetings (next: 21-24 October, 2004 in Versailles, France) All ESID Countries Austria Belgium Croatia Czech- Republic Denmark Estonia Finland France Germany Greece Hungary Iceland Ireland Israel Italy Netherlands Norway Poland Portugal Russia Serbia- Montenegro Spain Sweden Switzerland Turkey United- Kingdom President: Prof. L. D. Notarangelo, Brescia, Italy; Secretary: Prof. H. Wolf, Vienna, Austria Main patient registry 10,717 recorded cases of Primary Immunodeficiencies in Europe

4. Registry The existing ESID Registry Up-to-date patient- and research-databases The ESID Main Patient Registry The CVID Subregistry Requirements Time schedule Support for the documenting centers Summary Prospectives

5. What features should a patient- and research database have? m Longitudinal Analysis of a single patient and a cohort of patients m Cross-sectional Analysis of patient cohorts m Multivariate Analysis and complex database queries m Variable programming of queries m Easy implementation of new databases via XML-programming m Data-entry via electronic Import, Scanning-Function or manually m Connecting medical centers world-wide m Accessable any time from any place m Patient-Report-Generation m Recall-Function m Security: Implementation of rules for patient‘s data protection m Access: controlled by complex User-Role-Management

6. Concept and architecture of an internet based ESID database network User-Role management User-Password: Handles access to the ESID-database system

7. XML View ModelController DBJava2EnterpriseEdition Server XML Initialisierung Client access via Standard Internet Browser Server Client Thin Client-Server Architecture OperatingSystem: Unix

8. 3. Additional Subregistries on demand ESID Main Patient Registry CVID Subregistry DGS Subregistry NBS Subregistry XLA Subregistry HIGM Subregistry SCID Subregistry Neutropenia Subregistry... Additional Subregistries ESID Main Registry & Subregistries 2. CVID Subregistry 1. ESID Main Registry

9. The existing ESID Registry Up-to-date patient- and research-databases The ESID Main Patient Registry The CVID Subregistry Requirements Time schedule Support for the documenting centers Summary Prospectives

10. Core data-subset PATIENT: Sex, date of birth, region of residence (clustered in regions with > 30 millions inhabitants) DIAGNOSIS: Date of diagnosis, onset of symptoms, disease/diagnosis THERAPY: Date, drug, dose per weight, dose interval, route (oral / SC / IV), from, until, side-effects, reason stopped, compliance PHARMACO-ECON: Days in hospital, days missed at school, days missed at work IMMUNIZATIONS: Date, vaccine, postvaccinal titres LABORATORY: Date, time, label, value (IgG, IgA, IgM, CD3, CD4, CD8, CD19 or CD20, CD56, Leukocytes, Thrombocytes, Erythrocytes, Lymphocytes, Granulocytes, Hb, Eosinophils, Basophils, Macrophages) in percent or/and in absolute values

11. The ESID Main Registry

12. The ESID Main Registry

13. The ESID Main Registry

14. The ESID Main Registry

15. The existing ESID Registry Up-to-date patient- and research-databases The ESID Main Patient Registry The CVID Subregistry Requirements Time schedule Support for the documenting centers Summary Prospectives

16. Datamodel: CVID database-system

17. The CVID Subregistry

18. The CVID Subregistry

19. The CVID Subregistry

20. The CVID Subregistry

21. The CVID Subregistry

22. The CVID Subregistry

23. The CVID Subregistry

24. The CVID Subregistry

25. The CVID Subregistry

26. The CVID Subregistry

27. The CVID Subregistry

28. Registry The existing ESID Registry Up-to-date patient- and research-databases The ESID Main Patient Registry The CVID Subregistry Requirements Time schedule Support for the documenting centers Summary Prospectives

29.  Positive statement of data protection officer and/or ethics board  Signed consent form from patients  Database models Requirements

30. Data protection approval: source document

31. Ethics vote: source document

32.  Positive statement of data protection officer and/or ethics board  Signed consent form from patients  Database models Requirements

33. Consent form for patients

34.  Positive statement of data protection officer and/or ethics board  Signed consent form from patients  Database models Requirements

35. PID Classification & Steering committees

36. Registry The existing ESID Registry Up-to-date patient- and research-databases The ESID Main Patient Registry The CVID Subregistry Requirements Time schedule Support for the documenting centers Summary Prospectives

37. Time schedule Sept. 1st 2003Start of project Jan. 27th, 2004CVID-datamodel submitted Jan. 29th, 2004NBS-datamodel submitted Feb. 2nd, 2004DGS-datamodel submitted Feb. 19th, 2004osteopetrosis-datamodel submitted March 8th, 2004The beta-version goes online May 15th, 2004End of test drive June 15th, 2004The ESID-registry will go online with the ESID-main-registry and the CVID subregistry October 1st, 2004additional 3 subregistries implemented from there on:additional 4 subregistries per year

38. Registry The existing ESID Registry Up-to-date patient- and research-databases The ESID Main Patient Registry The CVID Subregistry Requirements Time schedule Support for the documenting centers Summary Prospectives

39. The ESID registry working party has made major steps towards an ”ESID Online Patient- and Research-Registry”. We are about to develop a multi-centred data collection system in European and Non-European countries for patients with Primary Immunodeficiencies. The data collected in the participating centres shall be pseudonymized and thereafter be entered and made accessible in a central online registry. The registry will consist of multiple 'disease-specific subregistries'. Data from e.g. national registries will be automatically transferrable to eliminate the need of a second registration. The system will enable the user to enter any data at any time for any visit. We are asking for yearly updates of the records. With PPTA (Plasma Protein Therapeutics Association), the major financial sponsor of this project, we are about to arrange a financial compensation for the use of secretarial help for the documentation. For this project, ESID is asking for support from all physicians and researchers involved in the diagnosis, care, treatment, and support of patients with PID. The bonus system is set up as follows:  ESID suggests to compensate for secretarial assistence with 5 € per documented patient for whom a core dataset (red fields) has been documented and 10 € for each documented patient for whom an extended dataset (blue fields) has been documented.  In addition, there shall be an annual award for the five best publications of the five disciplines (Antibody deficiencies, T-cell or combined deficiencies, Phagozytic disorders, Complement disorders, Other PIDs) within PID using data of the ESID registry of about EUR 2.000,00 per publication and an extra award of EUR 5.000,00 for the best publication over all.  Furthermore, a center which has reached a specific number of documented patients shall be rewarded by travel grants to either the ESID summer school or the biannual ESID scientific meetings. Free registration to the meetings is also beeing discussed.  Each center may install the database locally to be able to work with personalized data, since the application will be able to generate patient reports to be sent e.g. to the home-physician. In addition, the database will support features like 'recall functions' which will remember the physician if a patient has not shown up for his/her regular follow-up visit. There will be a patient consent to be signed to ensure that the patient supports the initiative. It will be the centers' responsibility to obtain the patient consent. However, all PID patient organizations so far supported this project since it is designed to increase awareness and diagnosis of PID and to facilitate research in the field. We are prepared to provide you with all documents you will need for patients consents and ethics approvals. Thank you for your collaboration! By now about 150 confirmations of intended colla- boration by single documentation centers Letter to the ESID members Bonus system:  Compensation for secretarial assistance (EUR 10 per patient per year)  Annual award for the best publications within PID using data of the ESID Registry  Travel grants to ESID meetings and summer school  Possibility to work with personalized data plus recall-functions

40. Registry The existing ESID Registry Up-to-date patient- and research-databases The ESID Main Patient Registry The CVID Subregistry Requirements Time schedule Support for the documenting centers Summary Prospectives

41. Industry access to a core dataset additional data for post licensing surveillance data for marketing advertisement, publicity close contact to a world- wide network of high- profile research institutions Patients optimize research implement standards for diagnosis and therapy improve quality of life meet the patient‘s needs support the spirit of ESID Physicians research across centers using a huge database enable genetic, and therapeutic trials within ESID secretarial assisitance automated patient reports Why support the ESID-online registry?

42. Registry The existing ESID Registry Up-to-date patient- and research-databases The ESID Main Patient Registry The CVID Subregistry Requirements Time schedule Support for the documenting centers Summary Prospectives for participating countries

43. Decision 1: Do I need a signed consent form for the registry in my country? Do I need a vote from my ethical review board? Decision 2: Do I wish to have a personalized version of the ESID registry as a national registry, running behind the the firewall of my university? Question 1: What do I need from ESID to facilitate the registration of my patients? Does my center have the technical requirements for runnig the ESID database? Question 2: Can I improve the ESID registry? Prospectives

44. The online patient and research database network Bodo Grimbacher MD; Dominic Veit MA; Barbara Frisch MA University of Freiburg, Germany ESID patient registries grimbacher@medizin.ukl.uni-freiburg.de frisch@medizin.ukl.uni-freiburg.de veit@medizin.ukl.uni-freiburg.de

46. Concept and architecture of an internet based ESID database network Security and Dataprotection Input requires a positive statement from the local data protection officer and a signed consent from the patient(s) or legal tutor (approved form provided in 6 languages) SSL encrypted data transmission Secure Server Net (audited Firewall of the Hospital of Freiburg) User-Role Authentication Passwords are stored in encrypted form Multiple-User-Roles restrict views and presented data Patient randomization (patient ID’s) Only coded data allowed (ONLY the patient’s physician can match a specific data-set with his patients) No demographical data or ‘free text’ that potentially directly identifies the patient is stored in the system Meet the standards set by FDA CFR 21 Part 11 for Good Clinical Practice and ISO 9001 for Quality Control

47. Concept and architecture of an internet based ESID database network The network structure ESID registry: Disease-specific subregistries A b Local patient registry a B... National patient registries Centers AIEOP CINECA Italy National DB Local physicians Hospitals/INGID ESID mutation databases IPOPI

48. Existing registries/databases in: Italy 04/03 Spain 09/03 Poland 10/03 Czech 11/03 Paris 12/03 Hannover 02/04 Munich 03/04 Ulm Belgium Hungary The Netherlands Portugal Sweden...