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.