Epidermolysis Bullosa/European Reference Network Registry meeting: Background summaries

Wed 8th 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 .................... 10 Providing the tools to support interoperable patient registries ................................................ 10

EPIRARE – Luciano Vittozzi .................................................................................. 12 Biography and the EPIRARE project ...................................................................................................... 12

RD-Action – Victoria Hedley ................................................................................ 13 Biography and the Joint Action for Rare Diseases, RD-Action .................................................... 13

openEHR – Ian McNicoll ...................................................................................... 13 About openEHR .............................................................................................................................................. 13

OpenApp – George Reynolds ............................................................................... 14 From Registry to Rare Disease Management System ..................................................................... 14

OSSE: Open Source Registry System for Rare Diseases in the EU – Holger Storf .... 15 Background .......................................................................................................................................................... 15 Aim of the Project............................................................................................................................................... 15 Concept ................................................................................................................................................................... 15 The OSSE Registry Toolkit ............................................................................................................................. 16

Proposed European Reference Network for Rare and Undiagnosed Skin Disease . 16 ERNs and skin disease ................................................................................................................................. 16

About the supporting eHealth group for the proposed ERN for Rare and Undiagnosed Skin Disease .......................................................................................................................................................... 16

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.

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:

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.

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 2003. 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

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

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 co-

morbidity 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).

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

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

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 (http://parent-wiki.nijz.si/) 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 (http://www.parent-ror.eu) 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.

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

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, (www.rd-action.eu) 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 2012-2015

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

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 inter-

related 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 real-

time comparisons to health factor norms.

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 open-

source 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 (https://download.osse-register.de/MDS_3.0.pdf). 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.

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 11179 Metadata Registry Standard) has to be defined within the metadata

repository first. Further information is available at http://www.osse-register.de/en/.

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

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.