Epidermolysis Bullosa/European Reference Network Registry meeting: Background summaries

Transcription

1 Epidermolysis Bullosa/European Reference Network Registry meeting: Background summaries Wed 8 th June 2016, Dublin, Ireland Table of Contents Introduction... 3 The Irish Skin Foundation Dmitri Wall... 3 About the Irish Skin Foundation Registry Project... 3 DEBRA Avril Kennan... 3 About DEBRA Ireland and DEBRA International... 3 A message from the DEBRA International President... 4 EB-CLINET Gabi Pohla Gubo & Helmut Hintner... 4 About the EB-CLINET registry project... 4 British Association of Dermatologists Dermatology and Genetic Medicine (BADGEM) Mozheh Zamiri & Neil Rajan... 5 About the BADGEM register for rare genetic skin disease... 5 UK Epidermolysis Bullosa Database System... 6 About the database... 6 EB Registry Freiburg Cristina Has & Leena Bruckner-Tuderman... 6 About the EB Registry of the EB Centre Freiburg... 6 Description... 6 Outcomes... 7 Italian EB registry Maya El Hachem & Gianna Zambruno... 7 An overview of the Italian EB registry: state of art... 7 The French National Database for EB Christine Bodemer... 8 French EB registries Alain Hovnanian... 9 Local registries and plans to establish a national registry... 9 The Prospective EB Longitudinal Evaluation Study (PEBLES) Jemma Mellerio... 9 An overview of the PEBLES study and the data it captures... 9 PARENT JA (PAtient REgistries initiative Joint Action) Ivan Pristaš Providing the tools to support interoperable patient registries EPIRARE Luciano Vittozzi Biography and the EPIRARE project... 12

2 RD-Action Victoria Hedley Biography and the Joint Action for Rare Diseases, RD-Action openehr Ian McNicoll About openehr OpenApp George Reynolds From Registry to Rare Disease Management System OSSE: Open Source Registry System for Rare Diseases in the EU Holger Storf Background Aim of the Project Concept The OSSE Registry Toolkit Proposed European Reference Network for Rare and Undiagnosed Skin Disease. 16 ERNs and skin disease About the supporting ehealth group for the proposed ERN for Rare and Undiagnosed Skin Disease... 16

3 Introduction Dear friends and colleagues, we are delighted to host the upcoming meeting, which we hope will enable an exciting collaboration. Many thanks for the contributions to this document, which provides an insight into the diverse backgrounds of the meeting s attendees. With best wishes, Alan, Avril & Dmitri The Irish Skin Foundation Dmitri Wall About the Irish Skin Foundation Registry Project The Irish Skin Foundation (ISF) was founded in 2011 with the purpose of assisting patients with all forms of skin disease in Ireland. To this end, the ISF identified the development of a patient-centric registry, facilitated by an interoperable, state-of-the-art, patient information management system as a priority. The establishment of a mutually beneficial and collaborative, national and international ecosystem, with broad stakeholder representation, was considered vital to support the development and maintenance of such a system. It is the hope of the ISF that this endeavour will create a technological and networked solution that will map many of the core components, across the multiple domains required to deliver high quality, dermatological care. A 3 year-plan has received full funding to deliver a nationally implemented system, that covers many of these components and domains, and which could serve as a proof-of-concept model that could easily be adopted and implemented by other groups geographically. To date this has resulted in the development in software that, it is hoped, will support the development of a European atopic dermatitis registry. This is currently being beta-tested in 3 European centres. DEBRA Avril Kennan About DEBRA Ireland and DEBRA International DEBRA Ireland is the Irish patient organisation for people affected by EB. We provide patient care, advocate for patients in policy and political spheres and are heavily involved in many aspects of research. We have been working with the Irish Skin Foundation over the last couple of years, on our mutual vision to improve patient care through the creation of a registry that supports clinical management, facilitates research and encourages patient involvement in their own care. Our involvement throughout has been in close consultation with our DEBRA International colleagues.

4 DEBRA International is the worldwide alliance of epidermolysis bullosa (EB) patient support groups, working in over 50 countries and growing. The aim of the organisation is to facilitate member groups and people living with EB to work together, in order to maximise quality of life and to promote the development of effective treatments for the condition as quickly as possible. A message from the DEBRA International President Dear EB Registry meeting attendants, It is a great pleasure to have all you attend this meeting, with the objective of setting the main principles and possibly, milestones, of this important activity. Today we represent all different stakeholders interested in the registry development. We all - patients representatives, researchers and healthcare professionals - are daily facing the challenge of how to prioritise our activities and actions in the different areas of our responsibilities. In the healthcare area, the decisions are often influenced by the reality of the urgent needs of EB affected people on the one hand and restricted resources on the other. We all can only make as good informed decisions as the quality and availability of information and data we have. The EB registries are one of the key elements that can influence many of our actions, help understanding better EB causes and natural history, influence research development, select patient s involvements in trials and monitor the trials success. The importance of creating EB patients registry is therefore unquestionable. Setting up the new EB patient registry sets us on a high risk journey though, where a number of decisions need to be made about methodologies, processes, technologies and governance with many different stakeholders involvement. This process will require time, a number of meetings, calls and follow ups, of course. I am sure with all the important professionals and the expertise present today, that demonstrate the strong will we all have to make this happen, we will achieve this important result soon. I would like to thank the Irish Skin Foundation for this commitment to EB and to thank you all for coming. My kindest regards Cinzia Pilo DEBRA International President EB-CLINET Gabi Pohla Gubo & Helmut Hintner About the EB-CLINET registry project EB-CLINET is a clinical network of EB centres and experts, which aims at establishing EB centres worldwide to improve medical care for people with EB, through exchange of knowledge and experience about EB and, by providing a basis for clinical trials, to accelerate the way to a cure for this disease. To date an EB-CLINET registry project has been addressed at three meetings:

5 Registry workshop, Vienna 2013 EB-CLINET meeting, Salzburg 2013 EB-CLINET meeting, London 2015 Numerous excellent initiatives in a number of countries have been recognised and considerable work has explored the needs that call for an international EB Registry, potential stakeholders, data required, governance, funding and technical and regulatory requirements. In the Vienna workshop, 5 general aims of EB registries were identified: 1. Recruitment for clinical trials 2. Genotype-phenotype correlation 3. Natural history of disease 4. Biobanking 5. Epidemiology A number of challenges were recognised: Funding Consent Legislative differences Data sharing agreement Data synchronisation Access Connecting local databases At the 2015 EB-CLINET meeting in London, existing and emerging initiatives and opportunities highlighted the need for a renewed effort to progress the vision of a collaborative EB-CLINET registry network. British Association of Dermatologists Dermatology and Genetic Medicine (BADGEM) Mozheh Zamiri & Neil Rajan About the BADGEM register for rare genetic skin disease Patients with rare genetic skin disease may wish to seek new treatments in clinical trials. Disease registration is a key focus of the BADGEM informatics group, as this will allow national data on numbers affected to be collated, which is crucial given the small numbers in rare diseases. We have been involved in the development of a secure register that will contain a minimal dataset (clinical diagnosis and genotype) on a broad range of rare genetic skin disease, that will initially pilot in Scotland, with a plan to include the rest of the UK. This data can then inform the planning and design of UK and EU wide rare skin disease trials, as well as allow for natural history studies of cohorts of patients for clinical research projects.

6 The register design has been developed following consultation amongst the BADGEM Informatics team, made up of dermatologists with a special interest in genetic skin disease. Advice has been sought from experts in other relevant specialties as well as direct discussion with patient groups. The register infrastructure has been created by the University of Dundee Health Informatics Centre (HIC) who have experience of working on similar national databases and provide a secure environment for data collection under the provisions of the Data Protection Act. Scotland-wide ethical and Caldicott Guardian approval is currently being sought. Patients who have been diagnosed with a genetic skin condition via dermatology services would then be provided with appropriate information regarding the register and be invited to participate. Consent would also be sought to be able to contact patients in the future about any future ethically approved research or therapeutic studies which may be relevant to that individual. This register has the potential to inform us how frequently different rare genetic skin diseases occur, and in addition, allow a more coordinated approach to the delivery of clinical trials. UK Epidermolysis Bullosa Database System About the database This database acts primarily as an Electronic Patient Record at four user sites across the NHS; Birmingham Children s Hospital, Solihull Hospital, Great Ormond Street Hospital and St Thomas s Hospital (clinical users and laboratory). Since 2002, it has gathered comprehensive data on all EB patients (2167 as of September 2015), including demographics, date of birth, date of death and diagnosis, though data is incomplete for patient with milder EB subtypes. EB Registry Freiburg Cristina Has & Leena Bruckner-Tuderman About the EB Registry of the EB Centre Freiburg Description: The EB Registry of the EB Centre Freiburg was established in It comprises personal, clinical and molecular genetic data of more than 1047 patients with all types of EB. All included patients have given their informed consent. The quality of the data is assured by weekly interdisciplinary conferences, in which every single case is discussed, and the diagnosis is validated before being incorporated into the Registry. The diagnoses are established according to the international consensus classification of EB 2014 (Fine et al., J Am Acad Dermatol 2014). The distribution of EB types in the EB Registry Freiburg is: 40.1% dystrophic EB, 27.2% EB simplex, 20.3% junctional EB, 4.6% Kindler syndrome, and 7.7% EB (type not specified). It reflects the fact that predominantly patients with severe EB types request molecular diagnostics and require specialized management. In more than 90% of cases, molecular

7 genetic diagnosis is available. Longitudinal clinical information of about 250 patients is available (natural history). Outcomes: Based on the EB Registry Freiburg incidence of EB in Germany was estimated at 1:25,000. New causative genes and new types of EBS and JEB have been described (Pigors et al. Hum Mol Genet 2011, Has et al N Engl J Med 2012) Genotype-phenotype correlations have been analysed and reported for dystrophic EB (Kern et al., J Invest Dermatol 2006; Kern et al., Br J Dermatol 2009), junctional EB (Kiritsi et al., J Med Genet 2011; Schumann et al., Br J Dermatol 2013), EB simplex (Arin et al., Br J Dermatol, 2010) and Kindler syndrome (Has et al, J Invest Dermatol 2006; Has et al, Br J Dermatol 2008; Has et al, Clin Genet 2015; Chmel et al, J Invest Dermatol 2015; Maier et al, J Invest Dermatol 2015). The first study of the natural history of the Kindler syndrome was published in collaboration with other European Centres (Has et al., Hum Mutat 2011). Study of the genetic basis and clinical outcome of severe generalized junctional EB in Germany has been performed in collaboration with other centres (Hammersen et al, in revision). Currently, the Registry serves for the selection of patients for clinical trials and studies. Participation at the international dystrophic epidermolysis bullosa registry (van den Akker, Hum Mutat 2011). The contribution of Elfriede Kirchner and Daniela Kirstein who run the registry and of all physicians who collected clinical data over the years is acknowledged. We thank the patients for their participation. Italian EB registry Maya El Hachem & Gianna Zambruno An overview of the Italian EB registry: state of art The first initiative for an Italian EB registry was started, in 1991, by Dr Gianluca Tadini (Milan) several years ago, and published in 2005 on the Italian Journal of Dermatology (G Ital Dermatol Venereol 2005;140:359-72). Currently, local EB registries are kept by major EB centers in Italy. However, the information contained in the registry is variable from center to center, a registry specific informed consent is usually not obtained, registry data are, in most cases, updated occasionally, and the registry format (e.g. Excel, or SQL database) is different from center to center. A project proposal for a pilot web-based National EB Registry has been submitted by the center of Milan (Dr. G. Tadini and Prof. S. Esposito), and two centers in Rome, Bambino Gesù Children s Hospital (Dr. M. El Hachem and Dr. G. Zambruno) and IDI, (Dr D. Castiglia) to

8 DEBRA Italy for funding. DEBRA has expressed interest and discussions are ongoing. If approved, the project foresees the inclusion of all Italian EB centers at the end of the pilot trial. The French National Database for EB Christine Bodemer The French national database for rare diseases (project driven by the ministry of health) aims at collecting data for all rare diseases patients followed up within FIMARAD (the French national network for rare skin diseases, certified by the French Health Ministry and coordinated by C Bodemer). To encourage a consensus at a national level to constitute a homogeneous data collection at the point of care for rare disease patients, a minimum data set for all rare diseases patients (MDS-RD) was established and validated. The MDS is composed of 58 data elements divided in 6 categories: patient administrative, family history, encounter, condition, medication, and research participation questionnaire. In order to facilitate the integration on their daily routine data capture tools, the minimum data set is now being integrated within the national health information framework to enable national interoperability between electronic health care records applications of more than 60 university hospitals and the national BNDMR infrastructure. The objectives of the data collection are: (i) enable descriptive epidemiology for all RDs: prevalence, incidence of disease(s), (ii) care provision assessment, (iii) expert centre care activity measurements; (iv) undiagnosed cases characterization and time to diagnose analysis, (v) genotype to phenotype correlation analysis, (vi) identify RD patients within the care setting for research. In a second phase, the project will enable further analysis when record-linkage with other national databases will be set: (i) medico-economic studies, (ii) care pathways documentation, (iii) mortality and comorbidity studies. The French minimum data set for rare diseases was published internationally and validated at European level by the European expert group of rare diseases. The actual data collection is made by 1/3 of expert centres. The future interoperability framework of the project should dramatically increase the coverage of the data collection at national level. The data collection is set and accompanied by the French local RD thematic networks in order to set the necessary links between human actors and data collection methods. In Paris the certified centre for genodermatoses and EB patients is MAGEC, (coordinator C Bodemer), involving the following hospitals: Necker-Enfant Malades Hospital (coordinator: C Bodemer), St Louis Hospital (coordinator E Bourrat) and Avicene Hospital (Coordinator F Caux). There are also in France other certified centres in Nice (coordinator JP Lacour), Toulouse (coordinator J Mazeereuw), Bordeaux (coordonator A Taieb/C Labrèze).

9 French EB registries Alain Hovnanian Local registries and plans to establish a national registry Currently, local registries are kept by reference EB Centers in France (at Necker (Prof. C. Bodemer), Saint-Louis (Dr E. Bourrat) and Bobigny (Prof. C. Prost) hospitals in Paris and at L Archet hospital (Pr JP Lacour) in Nice), as well as by Prof. Hovnanian s laboratory at the Imagine Institute at Necker hospital in Paris. The information contained in these registries varies and is different from center to center. There is a project to establish a national EB registry through a national network (FIMARAD), with data management at the Imagine Institute. However, the rules of use of this registry have to be better defined in order to benefit EB patients and their families and to facilitate clinical studies, research projects and innovative treatments in the respect of each contributing center and laboratory. The Prospective EB Longitudinal Evaluation Study (PEBLES) Jemma Mellerio An overview of the PEBLES study and the data it captures The Prospective Epidermolysis Bullosa Longitudinal Evaluation Study (PEBLES) is a study looking at the natural history of recessive dystrophic EB in individuals of all ages from birth throughout life. It is being run jointly at St Thomas' and Great Ormond Street, London, recruiting from the EB services there. It was established to look in depth at the many different ways in which EB affects someone with RDEB, with a view to capturing cohort data across different types of RDEB at different ages, and also longitudinally within individuals. Children up to 10 years are seen every 6 months, and older children and adults are seen every 12 months. It has been recruiting for about 18 months now and includes data on approximately 50 patients. An electronic data capture tool has been developed to collect information which encompasses up to 2000 datasets. This information, once entered, is uploaded to a secure server and can then be interrogated via a dashboard to compare different parameters of interest. Some of the information is entered by the study nurse or doctor onto the tool at the time of doing the study, and other information is recorded by the patient/carer in the week or two before the study interview. Other information is retrieved from the patient's hospital or GP records. Only information and tests that would be undertaken as part of that person's routine care are recorded, with the exception of an additional serum sample for future analysis of biomarkers, if blood is being taken anyway. The following data is recorded as part of PEBLES: Demographic data (age, sex, etc) Previous skin biopsy and genetic diagnostic tests

10 Clinical subtype of RDEB Birth history and skin changes at birth Systematic review of EB-related problems e.g. eye, airway, musculoskeletal, oesophageal, bowel, bone, cardiac problems and SCCs Previous EB-related procedures e.g. oesophageal dilatations, hand surgery, gastrostomy Clinic appointments and inpatient spells Birmingham EB Severity Score iscoreb score Pain and itch questionnaire Quality of life measure Pubertal assessment (where appropriate) Medications Dressings (precise quantities and sizes) Information about who does dressings and whether paid or not Photographs of skin (standard views) The above information provides a very detailed picture about objective and subjective elements of an individual's EB, as well as data which means the costs of caring for their EB (e.g. carer costs, dressings, OP and IP hospital costs) can be calculated more accurately than in any previous studies. PARENT JA (PAtient REgistries initiative Joint Action) Ivan Pristaš Providing the tools to support interoperable patient registries PARENT Joint Action was a three-year project (May 2012-May 2015) co-funded by the European Commission and some Member States. The project represented a joint EU and Member States response to poor cross-border availability of health data for public health and research. The overall objective of PARENT JA was to support the EU Member States in developing comparable and interoperable patient registries in clinical fields of identified importance, thus enabling the use of secondary data for public health and research purposes in cross-organizational and cross-border setting. The importance of the PARENT JA relies on the development of tools of significant utility, not only for those involved in the day to day work in patient registries, but also for those trying to create a new one. The purpose of PARENT Framework, one of the deliverables of PARENT JA, is to provide Member States, patient registry holders and registry data users with the policies, guidelines, and tools necessary to support interoperable patient registries and exchange of data between them. It consists of a Knowledge Management Platform (holding documents such as Guidelines, State-of-the-art reviews and best practices), Information Technologies (IT) tools and models repository (consisting of software tools and services and links to external tools and services relevant for patient registry implementers

11 and holders) and Registry of Registries (providing structured search across a number of EU Patient Registries). Figure 1. Web view of the PARENT JA Methodological guidelines and recommendations for efficient and rational governance of patient registries The tools of PARENT are built having in mind easy, user-friendly, time- and place independent access to them. The Methodological Guidelines and Recommendations for Efficient and Rational Governance of Patient Registries ( enables the registry holders, governance bodies, financing institutions, researchers and others a comprehensive overview on necessary activities and structures to govern the registries, provide high quality data and re-use registry data. Over the course of the PARENT JA, two complete versions of the Registry of Registries tool ( have been created. The first was based upon an online questionnaire, which collected metadata on European patient registries and included a complete directory with various browsing functions. The second version of the RoR included the ability for registry holders to nominate new organisations and registries as well as edit their data, with links to the Registry Guidelines wiki tool. It allowed them to maintain and update the information, but also assess their registry(es), get guidance for improvement (based on knowlege dynamically compiled in the framework) and compare them to a freely selected comparison group.

12 Figure 2. Screenshot from the PARENT JA Registry of Registries version 2 The main activities needed to ensure continuity of what has been accomplished during the PARENT Joint Action include applying, maintaining, developing and disseminating PARENT deliverables as well as maintaining and adapting connections to ongoing stakeholders' activities. The continuation of further development of PARENT and PARENT output will take place in the context of JAseHN, EUnetHTA JA3 nd RD-JA. Registries and their holders, researchers, policy makers and other secondary users of registry data will have permission to put the PARENT Framework and tools to the test of addressing a variety of domain specific needs. Research programs will also offer a diversity of opportunities on development, through a combination of approaches and fields. In such a setting, the importance of maintenance and communication across applications of the Framework becomes truly essential. EPIRARE Luciano Vittozzi Biography and the EPIRARE project After a long period of research in Biochemical Toxicology, the development and assessment of toxicology tests and in the control of Standard Operating Procedures, L. V. joined the European Commission, Unit of Emerging, Rare and Communicable Diseases, as Seconded National Expert. There, he combined his scientific and technical experience with the basics of European co-operation and management in public health. In 2008, he joined the National Centre for Rare Diseases becoming Director of the Unit dealing with public health aspects and EU relations. He was responsible for the Italian National Registry of Rare Diseases and coordinated operatively several EU public health projects (EUGLOREH, EUROPLAN, the EU

13 Tender on Neonatal Screening Practices in Europe and EPIRARE), always facing the issues of existing data comparability and collation. In particular with the EPIRARE project, he addressed the need to facilitate the establishment of registries of rare disease patients and the collection of comparable data. A concept European platform was developed based on: 1) purposes, which could allow synergies among four basic stakeholders: patients, researchers and clinicians, health institutions and the pharma industry; 2) a common set of data elements fitting the platform purposes, which could be used as a menu for registries; 3) an encrypted identifier, based on personal details which are likely to be the basis of most patient identifiers, so that data linkage is feasible once that the patient authorizes it or a common encryption algorithm is defined by the health authorities at EU level. After the completion of the EPIRARE project, this concept has been tested and made operative with the implementation of two registries: one mainly driven by clinicians and another mainly driven by patients. RD-Action Victoria Hedley Biography and the Joint Action for Rare Diseases, RD-Action Victoria Hedley is a rare disease policy expert with experience and understanding of a wide range of topics across the rare disease spectrum. As Thematic Coordinator in the new Joint Action for Rare Diseases, RD-Action, ( she is responsible for facilitating the translation of the needs and priorities of the field into meaningful policies at the European level whilst maximising impact at the national/regional level. A major focus of this role is continuing to support the RD field in preparing for, and implementing, robust ERNs; for instance, Victoria has led the RD-ACTION Matchmaking tool and is spearheading the interactions with ehealth communities (she is a member of the RD-Action Task-Force on Interoperable data sharing in the framework of the operation of ERNs). From Victoria project-managed the EUCERD Joint Action working for Rare Diseases, as the main point of contact in the Newcastle University Coordinating team. Over the last three years this role entailed building and maintaining relationships with stakeholders from Competent National Authorities, academia, patient organisations and Industry, to ensure the specificities and unique needs of those living and working with rare diseases are addressed in expert policy guidance. Since 2013 Victoria has supported the National Rare Disease conferences and provided guidance to optimise national activities for rare diseases. She has organised and delivered workshops on the European level with a particular emphasis on cross-border healthcare, particularly on the topics of European Reference Networks and Cross-Border Genetic Testing for Rare Diseases. openehr Ian McNicoll About openehr

14 openehr is an open specification for health records standardisation that aims to provide a platform on which a variety of vendors and developers can compete to build high quality ehealth applications but where the underlying information is held in a standardised format that prevents vendor or technology lock-in. openehr also enables a much faster and flexible way of getting new and changing clinical ideas into ehealth systems and allows highly interoperable systems to be developed by the sharing of open-source, clinically-developed information components known as 'archetypes'. There are now examples of successful openehr-based applications across the world, from UK to Brazil, Norway, Australia and China, with a growing clinical and vendor community committed to open standards. OpenApp George Reynolds From Registry to Rare Disease Management System Established over 12 years ago, OpenApp is a successful software company specialising in healthcare with almost 30 employees. We are the main provider of healthcare analytics solutions to the Irish health care system (HSE) (healthatlasireland.ie). Over the last few years we have developed our skills to include Rare Disease registry software. We are developing registries for a variety of rare and acute diseases, including cystic fibrosis, alpha-1 antitrypsin deficiency, interstitial lung disease, autism, Tay- Sachs disease, multiple sulfatase deficiency, orthopaedics, haemophilia, phototherapy, atopic dermatitis and epidermolysis bullosa. At one time, registries were simple spreadsheets. They then evolved into a series of interrelated spreadsheets commonly referred to as 'spreadsheet hell'. Not so today. OpenApp Registry can evolve and expand into a full rare disease management system that provides all the clinical data required for Clinical Trials and Health Technology Assessments. Our vision is that a patient registry ought to be optimised for a disease and not limited by geographical area. It should be a system not just for research, but also for patients and clinicians. We believe that a registry should evolve into a patient-centric, rare disease management system with a: Patients portal Clinical portal Studies portal Genetic portal Using this ehealth, patient-centric approach, registries can integrate with multiple different systems including hospital based labs, radiography departments and IT systems. Doctor's notes, multi-disciplinary team reviews and automated assessment triggers can be integrated into the registry giving a longitudinal view of each patient s disease history along with realtime comparisons to health factor norms.

15 OpenApp believe ERNs represent a paradigm shift from acute, silo-based hospital ICT systems to disease based ICT systems providing pan-european rare and chronic ehealth care. We are working with several ERN groups and will be extending its current ehealth platform to include: Multidisciplinary team review Optimum clinical pathway Videoconferencing Cross boarder billing Audit trail for verification of services OSSE: Open Source Registry System for Rare Diseases in the EU Holger Storf Background In keeping with the European Council recommendations, Germany published a National Plan for Rare Diseases (RD) in August 2013, which includes 52 policy proposals to guide and structure actions in the context of rare diseases within the German health and social system. The project OSSE (Open-Source-Registersystem für Seltene Erkrankungen in der EU / Open Source Registry System for Rare Diseases in the EU), funded by the German Federal Ministry of Health, provides a reusable software for RD registries. Aim of the Project OSSE provides patient organizations, physicians, scientists and other parties with opensource software for the creation of patient registries. As a result, the national registry landscape is empowered to comply with European principles regarding the establishment of minimum data sets, the compliance to data quality standards, etc. (summarized in the EUCERD Recommendation on RD registries). In addition, the necessary interoperability between different registries is supported from the start and allows to federate those registries on a national and international level (e.g. distributed searches designed to comply with data protection requirements and preserve data sovereignty). Concept OSSE has defined and implemented a common data set (CDS) that should be held by all compliant registries ( Disease-specific additions can be collected and made available throughout the federated registries by defining them in a metadata repository (MDR). To meet the requirements of data protection, a template of required patient consent forms is provided along with a generic data protection concept taking into account the specificities of RD. A generic registry software was implemented and is distributed as an open source solution. It enables the handling of forms by providing an editor to read, modify and validate forms. Versioned persistency, secure authentication and an access management system is provided as well. As a proof of concept, the software is currently set up in two RD registries and will be employed during the first half of the year 2016.

16 The OSSE Registry Toolkit The backbone of OSSE is a registry toolkit that enables scientists with a basic IT background to build a registry for a specific rare disease. A form editor allows defining forms for longitudinal and basic medical data and of the corresponding data schema. Each field (including, inter alia, data type, ranges, measurement units and value sets according to ISO/IEC Metadata Registry Standard) has to be defined within the metadata repository first. Further information is available at Proposed European Reference Network for Rare and Undiagnosed Skin Disease ERNs and skin disease The European Commission recently launched a first call for interest to establish European Reference Networks (ERNs), groups of highly specialised providers across the EU. The call, open 16/03 21/06, will provide 2.5 million to support successful applicants for a maximum duration of 5 years. Furthermore, 1.2 million will be made available to fund the development of 3-4 new registries on rare diseases based on existing registries in Member States. Only successful ERNs will be invited to apply for this funding. The Genodermatoses Network was launched in 2004 and has been co-funded from 2008 to 2011 by the European Commission as a pilot ERN for Rare Disease. Since then, the Genodermatoses Network, which works in close collaboration with patient groups and alliances such as DEBRA International, has developed an inclusive approach to involve the network experts and centres taking care of patients with rare skin diseases. Under the lead of Professor Christine Bodemer, in partnership with Geneskin and EB-Clinet, the Genodermatoses Network is preparing a project proposal for an ERN on Rare and Undiagnosed Skin Disorders. About the supporting ehealth group for the proposed ERN for Rare and Undiagnosed Skin Disease A key enabler of ERNs will be strong ehealth-focused IT platforms to enable, for example, videoconferencing, image sharing, outcome measurement, research and clinical trial facilitation. Within the proposed ERN for Rare and Undiagnosed Skin Diseases, an ehealth committee has been established. This committee consists of Alan Irvine and Dmitri Wall, Matthias Schmuth, Kathrin Giehl and Frank Ückert, Martin Lablans and Holger Storf of The Open Source Registry System for Rare Diseases in the EU (OSSE). The group aims to support the needs of the clinical groups within the proposed ERN by proposing a collaborative approach that recognises the achievements and sovereignty of existing information systems (for example patient registries), by providing a means of appropriate data sharing amongst these systems, while also adopting information modeling processes that will enable the ERN to maximise its impact by developing consensus datasets that can underpin the development of new registries and systems. This will facilitate the development of cross-border, best

17 practice, collaborative clinical and research networks using state-of-the-art systems. These will aim to incorporate the recommendations of European projects such as PAtient REgistries initiative joint action (PARENT JA) and the EPIRARE project with respect to best practice registry development and rare disease registry establishment, respectively. The hope is that this meeting and collaboration will act as a prototype for the proposed ERN for Rare and Undiagnosed Skin Disorders, strengthening their chance of success and opening opportunities for further funding opportunities.