Application of the ERN model in European cross-border healthcare cooperation outside the rare diseases area : report of the expert panel on effective ways of investing in health (EXPH).
Date: 2018-12-07
Institutions: Directorate-General for Health and Food Safety
Subjects: European cooperation, cross-border cooperation, health care, health care system, health policy, illness, organisation of health care, patient's rights

APPLICATION OF THE ERN MODEL IN EUROPEAN 
CROSS-BORDER HEALTHCARE COOPERATION OUTSIDE 
THE RARE DISEASES AREA

Report of the  
Expert Panel on effective ways of  
investing in Health (EXPH)

Health

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ISBN 978-92-79-97291-1 

doi: 10.2875/211563 

EW-03-18-455-EN-N

EXPERT PANEL ON EFFECTIVE WAYS OF INVESTING IN HEALTH 

(EXPH) 

Opinion on 
Application of the ERN model in European cross-border 
healthcare cooperation outside the rare diseases area 

The EXPH adopted this opinion at the 11th plenary on 26 September 2018 
after public hearing on 25 September 2018 

Application of the ERN model in European cross-border healthcare cooperation  

About the EXpert Panel on effective ways of investing in Health (EXPH) 

Sound and timely scientific advice is an essential requirement for the Commission to pursue 
modern, responsive and sustainable health systems. To this end, the Commission has set 
up  a  multidisciplinary  and independent Expert Panel,  which  provides  advice on  effective 
ways of investing in health (Commission Decision 2012/C 198/06). 

The core element of the Expert Panel’s mission is to provide the Commission with sound 
and  independent  advice  in  the  form  of  opinions  in  response  to  questions  (mandates) 
submitted  by  the  Commission  on  matters  related  to  health  care  modernisation, 
responsiveness, and sustainability. The advice does not bind the Commission. 

The areas of competence of the Expert Panel include, and are not limited to, primary care, 
hospital  care,  pharmaceuticals,  research  and  development,  prevention  and  promotion, 
links with the social protection sector, cross-border issues, system financing, information 
systems and patient registers, health inequalities, etc. 

Expert Panel members 
Christian Anastasy, Pedro Barros, Margaret Barry, Aleš Bourek, Werner Brouwer, Jan De 
Maeseneer (Chair), Dionne Kringos, Lasse Lehtonen, Martin McKee, Liubove Murauskiene, 
Sabina Nuti, Walter Ricciardi, Luigi Siciliani and Claudia Wild 

Contact: 

European Commission 
DG Health & Food Safety 
Directorate B: Health Systems, medical products and innovation 
Unit B1 – Performance of national health systems 
Office: B232     B-1049 Brussels 

SANCO-EXPERT-PANEL@ec.europa.eu 

The opinions of the Expert Panel present the views of the independent scientists who are 
members of the Expert Panel. They do not necessarily reflect the views of the European 
Commission nor its services. The opinions are published by the European Union in their 
original language only. 

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Application of the ERN model in European cross-border healthcare cooperation  

ACKNOWLEDGEMENTS 

Members of the Working Group are acknowledged for their valuable contribution to this 
opinion. 

The members of the Working Group are: 

Expert Panel members 

Chair    
Rapporteur  W. Ricciardi 

M. McKee 

Members 

S. Nuti  
L. Lehtonen 
D. Kringos 
A. Bourek 
J. De Maeseneer 
C. Anastasy 
L. Siciliani 

The declarations of the Working Group members are available at: 
https://ec.europa.eu/health/expert_panel/panel_members_en 

We are grateful to Dr Alice Walker, an ERASMUS scholar at the London School of Hygiene 
and Tropical Medicine, who conducted the interviews with ERN contacts, to Dr Domenica 
Taruscio, Director of the National Centre for Rare Diseases of Istituto Superiore di Sanità, 
and to Enrica Manzato, a student at Sant'Anna School of Advanced. Studies of Pisa, who 
assisted with editing. 

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Application of the ERN model in European cross-border healthcare cooperation  

SUMMARY 

European Reference Networks (ERNs) were created by the Directive on the Application of 
Patients’  Rights  in  Cross-Border  Healthcare.  They  offer  a  means  by  which  patients  with 
rare  and  complex  diseases can  gain  access to highly  specialised  knowledge  from  across 
the European Union. The Expert Panel has been asked to advise on areas that can benefit 
most from the ERN model, options for the new networks in the longer term and the roles 
that they might assume, and how best national health systems could integrate networks 
into their national frameworks. 

ERNs are still a very new concept, having been launched in March 2017. So far, 24 have 
been established, bringing together over 300 hospitals from 26 Member States. Given the 
short time that they have been operating, the Expert Panel concluded that it was premature 
to draw any conclusions on their effectiveness. Instead, it sought to understand how other 
networks with similar goals have operated within member states and the lessons that have 
been learned, coupled with interviews with two of the coordinators of existing ERNs. 

The Expert Panel concluded that, while ERNs have considerable potential to improve the 
care of patients with rare diseases across the EU, both through advice on the management 
of  individual  patients,  as  well  as  through  collaboration  on  research  and  development  of 
guidelines,  it  is  not  yet  possible  to  ascertain  the  extent  to  which  these  goals  will  be 
achieved.  The  Expert  Panel  also  identified  several  issues  which,  even  at  this  stage, 
appeared  to  need  to  be  addressed,  including  long-term  financial  sustainability  and  the 
implementation of effective IT systems. 

Turning to the specific questions asked of the Expert Panel, we firstly concluded that the 
current  criteria  for  establishing  a  ERN,  as  a  means  of  improving  the  management  of 
patients  with  rare  and  complex  diseases,  was  appropriate.  The  ERN  concept  does  not 
address other issues raised for our consideration, such as remote areas and border regions, 
or the development of new medicines or interventions, for which there are alternative and 
more appropriate mechanisms. We were also asked about the scope to extend the scope 
of  ERNs  to  other  areas  such  as  the  care  of  people  who  are  homeless  or  emergency 
situations.  In  both  cases,  we  believe  that  there  are  better  alternative  mechanisms  to 
achieve the intended goals. Secondly, we examined the scope of the ERNs, and in particular 
their  relationship  with  research  and  guideline  development.  Given  the  current  state  of 
implementation, it is not possible to come to a definitive conclusion, but we were persuaded 
by the arguments that there is considerable scope for incorporating these additional roles 
beyond  the  immediate  objective  of  providing  advice  on  individual  patients.  This  will, 
however, require dedicated resources, some of which will have to come from other sources. 
Thirdly, while reinforcing the importance of ERN is to link with national health systems, the 
diversity  of  systems  within  Member  States  makes  it  impossible  to  provide  detailed 
guidelines  for how this can  best  be  made to  work.  This is  another  area  where it  will  be 
important to monitor the implementation of the existing ERNs and disseminate the lessons 
that arise from their experiences. 

Opinion to be cited as:  

EXPH (EXpert Panel on effective ways of investing in Health),  
Application of the ERN model in European cross border healthcare cooperation outside 
the rare diseases area, 26 September 2018 

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Application of the ERN model in European cross-border healthcare cooperation  

© European Union, 2018 

ISSN 2315-1404 
doi:xxxx 

ISBN   
ND-xxx 

http://ec.europa.eu/health/expert_panel/index_en.htm 

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Application of the ERN model in European cross-border healthcare cooperation  

TABLE OF CONTENTS 

ACKNOWLEDGEMENTS ........................................................................................... 3 

SUMMARY ............................................................................................................. 4 
BACKGROUND ....................................................................................................... 7 
TERMS OF REFERENCE ........................................................................................... 9 
OPINION .................................................................................................... 10 
1. 
Introduction .......................................................................................... 10 
1.1. 
1.2. 
Legal basis ............................................................................................ 14 
1.3.  What do we know about existing ERNs? .................................................... 15 
1.3.1. 
How do networks benefit patients? ..................................................... 16 
1.3.2.  What are the factors influencing the success of ERNs? .......................... 17 
1.3.3.  What issues should be addressed to ensure proper functioning of ERNs? . 18 
How to evaluate the effectiveness of ERNs? .............................................. 20 
Are there other areas where European Reference networks might be 

1.4. 
1.5. 
appropriate? .................................................................................................... 25 
Should the ERN model be used as a whole? .............................................. 29 
1.6. 
1.7. 
How should national health systems integrate such networks into their national 
framework? ...................................................................................................... 31 
Proposed criteria for establishing ERNs ..................................................... 33 
1.8. 
CONCLUSIONS AND RECOMMENDATIONS .............................................................. 34 
REFERENCES ...................................................................................................... 37 

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Application of the ERN model in European cross-border healthcare cooperation  

BACKGROUND  

Member States seek to give their citizens access to the best possible health services. This 

has led to various arrangements for cooperation between them. The European Union, on 

the  basis  of  Article  168  of  the  TFEU,  plays  an  important  role  in  complementing  and 

supporting  national  health  policies,  encouraging  cooperation  among  Member  States  and 

promoting  coordination  between  their  programmes.  This  general  mandate  was  further 

defined in Directive 2011/24/EU on the application of patients’ rights in cross-border health 

care. 

The  European  Reference  Networks  (ERNs)[1]  are  a  prime  example  of  structured  and 

voluntary collaboration among the EU Member States in the field of healthcare.  

These cross-border networks bring together healthcare providers across Europe to tackle 

rare and complex diseases that require highly specialised healthcare knowledge. The ERNs 

give access to a much larger, cross-border pool of expertise and knowledge, increasing the 

chances  of  patients  receiving  the  best  advice  to  treat  and  diagnose  their  diseases.  By 

assembling a large pool of patient data, they will, in the longer term, facilitate large clinical 

studies  to  improve  the  understanding  of  diseases  or  support  the  development  of  new 

medicinal  products.  Commissioner  Andriukaitis  highlighted  the  many  opportunities  for 

cooperation provided by the ERNs, referring to them as a backbone on which a European 

health data eco-system could be built [2]. 

Although the Directive makes particular reference to rare diseases, it has been suggested 

that other conditions requiring specialized resources or expertise could also benefit from 

the  idea  of  networking  to  provide  high-quality  and  cost–effective  care  [3].  Could  the 

experience  gained  in  cross-border  collaboration on  rare  diseases  be transferred  to other 

health topics? To answer this question, it is necessary to assess what the gain in cross-

border cooperation is, what areas might potentially be amenable to this approach and what 

possibilities exist to realise this potential, as well as what the financial implications would 

be. 

Rare diseases affect 6-8% of the population and as a group are an important public health 

problem. Many of the more prevalent diseases with the highest mortality rates in Europe, 

such as cardiovascular diseases (accounting for 34% of all deaths among men and 40% 

among women), cancer (30% men, 24% women) and respiratory diseases (9% men and 

8% women) [4], are successfully treated at national level, although there are likely to be 

specialised  areas  where  European  cooperation  could  bring  further  improvements  in 

outcomes. There are also specific treatment or diagnostic challenges (e.g. genetic testing 

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Application of the ERN model in European cross-border healthcare cooperation  

or access to expensive infrastructure, such as positron emission (PET) imaging and proton 

beam  therapy)  as  well  as  the  delivery  of  services  in  border  areas,  where  cross-border 

collaboration  brings  added  value  [5].  There  may  also  be further  roles,  with  the  Council 

Conclusions  of  June  2017  suggesting  that  the  ERNs  could,  within  their  current  scope, 

assume a role in highly specialized training and continuous professional development for 

health professionals [6, Sec. 3a].  

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Application of the ERN model in European cross-border healthcare cooperation  

TERMS OF REFERENCE 

The Expert Panel's opinion on the application of the ERN model outside the rare diseases 

area would help to prepare future calls for new networks, by presenting the possibilities, 

outcomes and expected difficulties of a broader cooperation. 

The Expert Panel is requested to analyse the following: 

(a)  What  are  the  areas  that  can  benefit  most  from  the  ERN  model  of  cross-border 

cooperation? Should the selection process take into account: 

o the nature of disease (prevalence, complexity), 

o resources of the geographical area (small countries, remote areas, border regions), 

o medical intervention (treatment method or product), 

o specific goal of such a cooperation (e.g. creating new medicine)? 

(b) The Panel should also address aspects related to the implementation of the ERN model 

and advise on the different options for the long-term nature of new networks. Should the 

ERN  model  be  used  as  a  whole  (covering  diagnosis  and  treatment,  research,  training, 

knowledge generation…) or only include specific modules of collaboration depending on the 

need (e.g. only data gathering for Artificial Intelligence or genetic testing)? 

(c)  How  would  national  health  systems  integrate  such  networks  into  their  national 

framework? What are the difficulties to expect at national level? What would be the best 

national approach in the aspect of referral, financing and changes required in national legal 

systems? 

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Application of the ERN model in European cross-border healthcare cooperation  

1.  OPINION 

1.1. 

Introduction 

Ever since the Treaty of Maastricht, the European Union has recognized the contribution 

that cooperation in health services can bring to the people of Europe, while respecting the 

rights of Member States to decide how they will organize health services within their own 

national borders. The 2011 Directive on the Application of Patient’s Rights in cross-border 

care (cross-border directive) sets out the conditions under which a patient may travel to 

another EU country to receive medical care and reimbursement. It covers healthcare costs, 

as well as the prescription and delivery of medications and medical devices. In addition, 

the directive established the principle of voluntary cooperation between healthcare units 

in Member States in highlight specialized healthcare. In accordance with the article 12 of 

the Cross-Border Directive ERNs were established in 2017 as cross-Europe virtual health-

provider networks, aiming to facilitate discussion on complex or rare diseases that require 

highly specialized knowledge or treatment. Although the Directive does not define these 

networks  precisely,  it  envisages  the  creation  of  a  means  of  sharing  of  knowledge  and 

expertise,  concentrating  resources  and  patients,  and  thereby  improving  diagnosis  and 

treatment for those whose conditions are sufficiently rare that it will be difficult to provide 

appropriate treatment, especially in small Member States. Furthermore, article 13 of the 

Cross-Border  Directive  aims  to  make  patients,  health  professionals  and  those  bodies 

responsible for the funding of healthcare aware of the possibilities offered by Regulation 

(EC) No 883/2004 for referral of patients with rare diseases to other Member States even 

for diagnosis and treatments which are not available in the Member State of affiliation. 

The expectation of ERNs is that they will offer the following benefits: 

• 

 access to a much larger, cross-border pool of expertise and knowledge, increasing the 

chances of receiving the best advice to diagnose and treat their diseases, particularly 

for small Member States; 

• 

 bringing  together  patients  and  resources,  enabling  economies  of  scale  for  accessing 

treatment for rare diseases; 

• 

 gathering  a  larger  pool  of  patient  data,  thereby,  in  the  longer  term,  facilitate  large 

clinical studies to improve the understanding of diseases or support the development 

of new medicinal products. 

Historically, certain bilateral arrangements did exist, with varying degrees of informality, 

especially  in  the  smallest  Member  States  such  as  Malta  or  Cyprus,  or  within  the  Nordic 

countries.  However,  the  new  concept  offers  a  stronger  European  legal  basis  for  this 

approach, enabling more people to access them. 

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Application of the ERN model in European cross-border healthcare cooperation  

Starting  from  March  2017,  24  ERNs  have  been  established,  bringing  together  over  300 

hospitals from 26 Member States (MS): the number of MSs participating in each ERN varies 

between 8 and 19, and the number of reference centres in each MS varies between 1 and 

21 (with many reference centres taking part in more than one ERN) (Figure 1) [7].  

Figure 1: 

The ERN concept 

Source: https://ec.europa.eu/health/ern/work_en 

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Application of the ERN model in European cross-border healthcare cooperation  

The names and disease areas of the ERNs are listed in Table 1. 

Table 1: 

European Reference Networks 

European Reference 
Network on inherited and 
congenital anomalies  
European Reference 
Network on congenital 
malformations and rare 
intellectual disability  
European Reference 
Network on respiratory 
diseases  
European Reference 
Network on paediatric 
cancer (haemato-oncology)  

European Reference 
Network on hepatological 
diseases  
European Reference 
Network on connective 
tissue and musculoskeletal 
diseases  
European Reference 
Network on 
immunodeficiency, 
autoinflammatory and 
autoimmune diseases  
European Reference 
Network on neurological 
diseases  

Endo-ERN  

ERKNet  

ERN BOND  

European Reference 
Network on endocrine 
conditions  
European Reference 
Network on kidney 
diseases  

European Reference 
Network on bone 
disorders  

ERNICA  

ERN ITHACA  

ERN LUNG  

ERN CRANIO   European Reference 

ERN PaedCan  

ERN RARE-
LIVER  

ERN 
ReCONNET  

ERN RITA  

ERN-RND  

Network on 
craniofacial anomalies 
and ENT disorders  

ERN EpiCARE   European Reference 

Network on epilepsies  

ERN 
EURACAN  

ERN 
EuroBloodNet  

European Reference 
Network on adult 
cancers (solid 
tumours)  
European Reference 
Network on 
haematological 
diseases  

ERN 
eUROGEN  

ERN EURO-
NMD  

ERN EYE  

ERN 
GENTURIS  

ERN GUARD-
HEART  

European Reference 
Network on urogenital 
diseases and 
conditions  
European Reference 
Network on 
neuromuscular 
diseases  
European Reference 
Network on eye 
diseases  
European Reference 
Network on genetic 
tumour risk 
syndromes  
European Reference 
Network on diseases 
of the heart  

ERN Skin  

European Reference 
Network on skin disorders  

ERN 
TRANSPLANT-
CHILD  
ERN  

ERN  

European Reference 
Network on transplantation 
in children Metab 
European Reference 
Network on hereditary 
metabolic disorders VASC 

European Reference 
Network on multisystemic 
vascular diseases 

Source: https://ec.europa.eu/health/sites/health/files/ern/docs/2017_brochure_en.pdf 

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The ERNs must meet certain criteria, set out in Box 1.  

Box 1:  

 Features and functions of ERNs 

Key Features: 

•  The  process  and  criteria  for  establishing  an  ERN  and  for  determining  eligibility  of 

Centres of Expertise and healthcare providers to join are established in the Commission 

Delegated Decision (2014/286/EU). 

•  ERNs  must  fulfil  criteria  for  implementation  and  evaluation,  including  being  patient-

centred  and  clinically  led,  with  a  minimum  of  10  members  in  at  least  8  countries, 

subject to robust independent third party assessment, and endorsed and approved by 

National Authorities. 

Key Functions:  

•  To  review  a  patient’s  diagnosis  and  treatment,  ERN  coordinators  convene  ‘virtual’ 

advisory panels of medical specialists across different disciplines, using a dedicated IT 

platform and telemedicine tool called the Clinical Patient Management system (CPMS). 

This allows expertise travel to the patient, rather than vice versa. 

• 

It  allows  sharing  of  expertise  to  diagnose,  follow-up,  and  manage  patients,  and 

facilitates  a  multidisciplinary  approach,  as  well  as  collaboration  and  learning  across 

centres of expertise and networks at national and international level.  

•  The focus is first on diagnosis and treatment by providing tools for collaboration and 

virtual consultations. However, there are clear potential research applications. 

•  These  functions  support  the  development  of  good  practice  guidelines  and  outcome 

measures for quality control, as well as contributing to research. 

Source: authors’ compilation from https://ec.europa.eu/health/ern_en 

All Networks and their Members should be periodically evaluated, at the latest every five years 

after their approval or last evaluation. 

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Application of the ERN model in European cross-border healthcare cooperation  

1.2. 

Legal basis 

ERNs  were  created  within  the  framework  of  European  legislation  on  cross  border  care, 

presented in detail in the Expert Panel’s report on Cross-border cooperation [5]. The key 

elements are summarized again in this section. 

European  Union  policy  in  the  field  of  health  is  aimed  at  complementing  and  supporting 

national health policies, encouraging cooperation between Member States and promoting 

coordination between their programmes. Article 168.2 of the Treaty on the Functioning of 

the  European  Union  (TFEU)  (European  Union  2012)  states:  “The  Union  shall  encourage 

cooperation  between  the  Member  States  in  the  areas  referred  to  in  this  Article  and,  if 

necessary,  lend  support  to  their  action.  It  shall  in  particular  encourage  cooperation 

between  the  Member  States  to  improve  the  complementarity  of  their  health  services  in 

cross-border areas. Member States shall, in liaison with the Commission, coordinate among 

themselves  their  policies  and  programmes  in  the  areas  referred  to  in  paragraph  1.  The 

Commission  may, in close contact  with the  Member  States,  take  any useful  initiative to 

promote  such  coordination,  in  particular  initiatives  aiming  at  the  establishment  of 

guidelines  and  indicators,  the  organisation  of  exchange  of  best  practice,  and  the 

preparation  of  the  necessary  elements  for  periodic  monitoring  and  evaluation.  The 

European Parliament shall be kept fully informed.”  

The general mandate contained in the Treaty has been spelled out in Directive 2011/24/EU 

on  the  application  of  patients’  rights  in  cross-border  health  care  [5].  In  addition  to  the 

objectives of establishing rules for facilitating access to safe and high-quality cross-border 

health  care  and  ensuring  patient  mobility  in  the  Union,  the  Directive  aims  to  promote 

cooperation  on  health  care  between  Member  States  (Recital  10).  Recital  50  calls  upon 

Member  States  to  “facilitate  cooperation  between  healthcare  providers,  purchasers  and 

regulators of different Member States at national, regional or local level in order to ensure 

safe,  high-quality  and  efficient  cross-border  healthcare.  This  could  be  of  particular 

importance in border regions, where cross-border provision of services may be the most 

efficient  way  of  organising  health  services  for  the  local  population,  but  where  achieving 

such cross-border provision on a sustained basis requires cooperation between the health 

systems of different Member States”. 

The areas and modes of cooperation are further specified in Chapter IV of the Cross-border 

directive. They include, in the first place, an obligation for Member States to render mutual 

assistance to implement the Directive, “including cooperation on standards and guidelines 

on quality and safety and the exchange of information, especially between their national 

contact  points”  (Article  10.1).  This  also  relates  to  exchanging  information  (through  the 

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Internal Market Information (IMI) system) on the right to practice of health professionals 

registered in one of  the  Member States  (Article  10.4).  In  addition,  Chapter  IV  creates  a 

concrete  basis  for  cooperation  and  action  in  specific  areas  that  have  been  identified  as 

particularly  relevant:  mutual  recognition  of  medical  prescriptions  (Article  11),  European 

Reference Networks (Article 12), rare diseases (Article 13), e-health (Article 14) and health 

technology  assessment  (Article  15).  This  does  not,  in  principle,  preclude  cooperation  in 

other fields as Article 10.2 also provides for a general commitment for Member States to 

facilitate cooperation. 

Rather  than  providing  an  exact  definition,  Article  12  of  Directive  2011/24/EU  lists  the 

objectives and characteristics for ERNs to qualify as such. Their functions and features are 

set out in the Directive (Box 1), and include provision of the knowledge and expertise to 

diagnose, follow-up, and manage patients, with evidence of good outcomes; employment 

of a multidisciplinary approach; possession of a high level of expertise, coupled with the 

ability to produce guidelines for good practice and to implement outcome measures and 

quality control; to contribute to research; to organize teaching and training activities; and 

to  collaborate  closely  with  other  centres  of  expertise  and  networks  at  national  and 

international level (Article 12.2). 

While there is formally no legal obligation for Member States to engage proactively in each 

of  the  forms  of  cross-border  collaboration,  except  in  relation  to  some  elements  such  as 

recognition  of  prescriptions  issued  in  another  Member  State,  the  European  Commission 

(EC) is entrusted by the mandate to “encourage cooperation between Member States in 

the areas set out in Chapter IV of this Directive and […], in accordance with Article 168(2) 

TFEU, take, in close contact with the Member States, any useful initiative to facilitate and 

promote  such  a  cooperation”  (Recital  51).  More  specifically,  Article  10.3  calls  for  the 

Commission  to  “encourage  Member  States,  particularly  neighbouring  countries,  to 

conclude  agreements  among  themselves”.  This  also  includes  specific  action  on  border 

regions: “The Commission shall also encourage the Member States to cooperate in cross-

border  health  provision  in  border  regions.”  (Article  10.3  in  fine).  One  way  for  the 

Commission to do so is “by identifying major obstacles to collaboration between healthcare 

providers  in  border  regions,  and  by  making  recommendations  and  disseminating 

information  and  best  practices  on  how  to  overcome  such  obstacles”  (Recital  51). 

Furthermore,  the  Commission  can  adopt  delegated  and  implementing  acts  to  organise 

cooperation in certain areas, e.g. medical prescriptions and European reference networks. 

1.3. 

What do we know about existing ERNs? 

As has been noted, ERNs are a very new concept and experience in their operation is very 

limited. The  existing  ERNs have  only  been operational  since  2017  and  a  relatively  small 

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number of patients have been referred, so it is too early to determine how effective they 

have been.  

To  inform  our  work  we  have  undertaken  interviews  with  two  ERN  co-ordinators,  Franz 

Schaefer, coordinator of ERKNET: European Reference Network for Rare Kidney Diseases, 

a consortium of 38 expert paediatric and adult nephrology centres in 12 Member States, 

and Marissa Tejedor Botello, project manager for TransplantChild, the ERN for Paediatric 

Transplantation,  including  both  Solid  Organ  Transplantation  (SOT)  and  Hematopoietic 

Stem Cell Transplantation (HSCT).  This ERN scope is a cross-cutting approach to supports 

common  areas  in  different  types  of  transplants  as  immunosuppression,  rejection, 

tolerance, risk of infection and psychosocial wellbeing, facing the transplant as `A process 

approach instead of a disease/organ approach´. 

1.3.1.  How do networks benefit patients? 

We first asked how networks benefit patients. Two main ways were identified: the pooling 

of expertise and the pooling of patients. The pooling of expertise is achieved by convening 

specialists from reference centres and make them agree on common standards of medical 

management  (which  should  improve  management  of  all  patients  being  treated  in  the 

centres  due  to  knowledge  sharing  and  development),  and  through  uploading  individual 

challenging cases to an online Clinical Patient Management System (CPMS). Once a case 

is referred and uploaded, a panel of experts is selected, depending on the specific expertise 

needed.  Clinical  details  are  reviewed,  and  an online  chat  facility enables  communication 

between the primary clinician and the expert panel. A report is then produced, providing 

the primary clinician advice for patient management. 

This  ability  to  pool  and  share  expertise,  resources,  and  experience  for  rare  conditions 

requiring complex treatment was seen by both interviewees as the main benefit of the ERN 

model. Coordination of experts on rare diseases has resulted in standardized assessment 

of more than 100 and final endorsement of 39 existing guideline documents by ERKNet, 

as well as the initiation of 7 new clinical practice recommendations by the thematic expert 

workgroups.  Moreover,  continuous  monitoring  and  benchmarking  of  center-specific 

performance and outcome indicators has been initiated by ERKNet as part of a network-

wide registry, which is hoped to result in continuous improvement of the quality of care.  

The second main benefit is creating a critical mass of patients: collecting and coordinating 

experience in treating patients with rare conditions requiring complex treatment allows the 

development of registries (ERKNet) and provides a platform for research.  Indeed, since 

the  sample  size  required  for studies  can  vary  greatly,  even the  pooling of  relatively  few 

cases can result in new opportunities for research [8]; of course, the higher the number 

16 

 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

of cases registered, the wider the scope of potential studies. While TransplantChild is an 

ERN focused on a procedure rather than a disease, the conditions of rarity and complexity 

are satisfied. Moreover, given the rarity of childhood transplants, and due to the similarities 

in immunosuppression protocols and complications, regardless of the organ transplanted 

or underlying condition, pooling experience in treating patients yields invaluable economies 

of scale for advancing knowledge and expertise on rare and complex treatments and with 

the challenge of creating the first registry in Europe in Paediatric Transplantation. 

Inevitably, members of networks will bring different degrees of expertise and capacity to 

contribute. In addition to those centres that join ERNs as full members, having satisfied 

the criteria of having the requisite expertise, others can join as ‘affiliates’ if these criteria 

are partially satisfied. This allows centres in countries without the means to create expert 

networks  to  gain  access  to  knowledge  in  highly  specialized  centres  in  other  European 

countries,  through  virtual  (CPMS)  or  physical  referral  of  patients,  and  participation  in 

publications and registry activities.  

1.3.2.  What are the factors influencing the success of ERNs? 

As noted, it is premature to undertake formal evaluations of the ERNs. We were advised 

that a working group is currently developing a monitoring framework for all ERNs. Agreed 

indicators (18 in total) aim to measure both patient-level and wider outputs, e.g. numbers 

of case uploaded to the CPMS system, cases closed, and publications generated.  

Both  interviewees  indicated  a  need  to  assess  potential  challenges  related  to  the  online 

patient management component of the ERN scheme, including equity of access (i.e. is the 

system  being  used  by  referring  centres  who  lack  expertise  and  thus  have  the  greatest 

need, or is it only being used by hospitals with sufficient capacity and resources to know 

how to use the new system?). It was felt that the planned expansion of the Networks to 

as yet unrepresented countries with less developed rare disease specialist services will be 

crucial to the success of the CPMS. 

It is clearly too early to assess whether the ERN model has resulted in improvements to 

patient  care.  Looking  to  the  future,  interviewees  remarked  that  evaluation  frameworks 

should  be  extended  to  measure  improvements  in  care  for  both  patients  referred  to  the 

CPMS, as well as the wider group of patients treated at participating centres. 

We sought insights into factors that might influence the success or otherwise of the ERNs, 

while recognising the limited experience so far. In particular, it is important to recognise 

that  there  is  no  clear  definition  of  what  “success”  means  for  ERNs:  in  extremely  broad 

terms,  they  aim  to  improve  treatment  and  care  pathways  for  patients  by  sharing 

17 

 
 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

information  among  health  professionals,  but  this  goal  has  not  yet  been  translated  into 

specific, measurable indicators. This crucial issue is expanded on in the following sections 

(“How to  evaluate  the  effectiveness of ERNs?”),  while here  we  focus on  the information 

gathered by asking about the effectiveness of ERNs in these general terms. 

The  first  factor  was  that  the  condition  or  the  procedure  around  which  the  network  was 

developed should be both rare and complex. It was noted that the current ERNs are not 

limited  to  rare  diseases.  The  TransplantChild  network  covers  all  cases  of  childhood 

transplants (i.e. a range of diseases/ conditions that lead to the need for transplant). While 

not  a  discrete  ‘disease’, transplants  require complex  management,  and  post-transplants 

complications are similar enough to warrant treatment within the same network.  

A second factor was that those who might interact with ERNs, as health professionals or 

patients,  should  be  aware  of  their  existence.  Networks  need  to  be  active  in  promoting 

themselves, in order to  ensure that the  network  fulfils the  potential  to  share  knowledge 

outside highly specialised centres. Coordinators remarked that in the initial stages of ERN 

setup, centres who join the network first were often those who need it least, since they 

were usually the centres with the highest concentration of expertise. ERKNET has observed 

that  representation  from  Eastern  European  countries  is  lacking.  The  real  need  for 

knowledge-sharing comes from those outside the very highly specialised centres. Effort is 

therefore needed by the network itself, as well as engagement with board of Member State 

representatives  and  national  health  systems,  to  promote  awareness  and  increase 

engagement by less developed specialist centres who may still be eligible for membership 

or  affiliate  membership.  TransplantChild  has  sought  to  increase  awareness  through 

engagement with professional organizations and meetings (e.g. the Meeting of Competent 

Authorities in transplantation), and by mapping children’s transplant centres in Europe. 

A  third  factor  was  the  need  for  well-functioning  and  user-friendly  IT  infrastructure. 

Interviewees referred to the time necessary to navigate and become familiar with new IT 

systems. Significant extra human resources are necessary in order to facilitate uptake and 

use of the CPMS system by clinicians.  

1.3.3.  What issues should be addressed to ensure proper functioning of ERNs? 

In addition, interviewees highlighted a set of criteria for effective working of the networks. 

There is a need for robust referral mechanisms within national health systems in order to 

ensure equitable access for patients to the centres in their countries that are participating 

in  ERNs.  This  involves  clarity  about  responsibilities  and  access  to  resources  for  patient 

management,  particularly  amid  fears  by  national  authorities  about  increased  healthcare 

costs resulting from easier access to highly specialised treatments. 

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Application of the ERN model in European cross-border healthcare cooperation  

We were told that Member States were increasingly seeing the added value of ERNs, given 

that  in  healthcare  overall  costs  will  often  be  saved  if  physical  referrals  are  replaced  by 

virtual consultations and the best possible treatment is given early on. However, given the 

lack of studies and the necessity to consider the costs of operating ERNs, it is unclear to 

what extent this holds true for rare diseases – thus, cost effectiveness is another crucial 

aspect to consider when evaluating ERNs, as will be highlighted in the next section (“How 

to evaluate the effectiveness of ERNs?”). 

As mentioned above, adequate funding is a critical issue. Significant investment is needed 

in  participating  specialist  centres,  both  for  individual  patient  management  and  wider 

activities  such  as  the  development  of  guidelines  and  registries,  which  require  additional 

resources beyond those provided as part of the ERN project. At present, interviewees felt 

resourcing responsibilities were unclear, with clinicians picking up the majority of the extra 

work,  which  was  not  necessarily  being  recognised  by  their  host  institutions.  Whereas 

payment  schemes 

for  physical  cross-border  referrals  are  well  established,  no 

reimbursement system exists for virtual consultations via the CPMS. In the case of ERKNet, 

alternative  time-limited  funding  streams  from  the  Commission  were  used  to  finance 

registry development. The process of guideline development was highly labour intensive, 

and largely product of ”clinicians’ enthusiasm”. These issues have clear implications for the 

sustainability of the concept. 

Also with regards to other ERNs, the sources of funding are unclear [9], with private donors 

and  patient-organized  campaigns  still  playing  an  important  role  in  providing  economic 

resources [10]. In addition, it is unclear who will provide for the treatment offered through 

ERNs [11]. 

This has clear implications for the sustainability of the concept [11], [12]: how are ERNs 

supposed to treat patients and develop guidelines, let alone monitor the outcomes and set 

up  mechanisms  for  continuous  improvement  (as  would  be  required  of  them  in  order  to 

assess  their  effectiveness)?  Furthermore,  how  can  they  be  expanded  to  other  areas,  if 

there is no clear, long term, sustainable method of funding neither for existing ones? 

Therefore, these funding issues must be addressed to guarantee the long-term existence 

of ERNs,  although  we recognise  that  it is  difficult  for  a  variety of  reasons.  For  instance, 

finding funds can be complicated because, at least in some cases, it entails high costs per 

se.  In  addition, it requires  agreements  between  countries  with  very  different  healthcare 

systems and a variety of third-party payers, with risk of free-riding occurring – unless ERNs 

themselves  set  the  price  for  treatments,  which  however  can  pose  problems  of  equity. 

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Notwithstanding these difficulties, funding remains a critical issue which must be solved in 

order for ERNs to continue functioning. 

The final issue that has been highlighted in the discussion on ERNs is the need for a clear 

management system and mechanism of governance [13]. Indeed, the tasks of ERNs are 

extremely complex, since they entail gathering information from many different patients 

and  clinicians  in  different  countries,  carrying  out  research  projects,  and  ultimately 

gathering  evidence  on  best  practices  and  making  it  available  to  those  involved  in  the 

subject in all Member States. All these activities are extremely challenging to carry out on 

such  a large  scale,  since  there  are  few  established  systems  for  doing  so  within national 

health  systems  [14].  For  these  reasons  it  has  been  suggested  that  coordinators  should 

ideally have expertise in networking, [12] with the ability to supervise all these different 

activities and ensure that the objectives of ERNs are being reached, which will often require 

support from a coordination team. 

1.4. 

How to evaluate the effectiveness of ERNs? 

As noted above, ERNs for rare diseases have been only implemented for one year: this is 

too short to evaluate their performance or identify ways how they could be improved. Thus, 

while in principle the ERN model can be a powerful tool to improve healthcare for European 

patients, more time and more and robust data are required to evaluate their impact. 

Given the inability to reach conclusions about the effectiveness of the ERNs, some insights 

into the issues that should be considered can be gained from a review of the operation of 

reference networks that exist already within Member States undertaken by the European 

Observatory [3]. This identified five dimensions relevant to gaining a better understanding 

of reference networks, their functions and the different shapes they assume. 

Table 2: 

 Dimensions of the operations of reference networks 

Governance 

Objectives 

Function 

Material scope 

Geographical scope 

•  Formal 

•  Efficiency 

• 

Informal 

•  Quality 

•  Peer 

•  Safety 

structure 

•  Hub-and-
spokes 

•  Organic 

• 

(Equity) 

•  Market 
position 

•  Referral of 
patients 

•  Transferring 
knowledge 

•  Prevalence 

•  EU-wide 

•  Cost 

•  Transnational 

•  Complexity 

•  National 

•  Rare 

• 

Interregional 

•  Critical 

•  Regional 

•  Chronic 

•  Common 

Source: W. Palm, I. Glinos, B. Rechel, and P. Garel, “Building European Reference 
Networks in Health Care,” European Observatory on Health Systems and Policies, 2013. 

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Application of the ERN model in European cross-border healthcare cooperation  

In addition, we propose a method that could be used to define what makes ERNs effective 

and evaluate them, drawing on examples of existing evaluation systems. 

In order to define what is an effective network, the first step is to define its mission. In the 

broadest possible terms, ERNs seek to improve outcomes, experience, and care pathways 

for patients with rare diseases. These networks should be able to facilitate and enhance 

exchange of information and competences among health professionals, thus sharing best 

practices and creating a virtual care community. The goal is to produce a multiplying effect, 

that is, to achieve an improvement in the care of these patients greater than what would 

be expected by simply adding together the single experts’ abilities. Indeed, the sharing of 

competence among network members should foster the creation of new knowledge, in the 

form  of  guidelines,  new  clinical  practices  and  recommendations,  or  scientific  literature, 

while also sharing advice on the diagnosis and treatment of patients in ways that would 

never have been possible had the health professionals worked alone. 

A  second,  but  nonetheless  important,  objective  is  the  ability  for  networks  to  become 

integrated in the national health care systems. In other words, what is the use of enormous 

amounts of expertise if they remain confined to the individual centres participating in the 

network? These centres must be able to reach all patients in their territories – and in other 

Member States, if no national reference centre has been established – in order to really 

make a difference to the care of these patients. Thus, ERNs are effective only in so far as 

they are inclusive, proactively reaching out to the populations they serve. 

Finally,  a  third  objective  of  ERNs  is  to  make  this  process  of  improving  treatment  and 

integration cost-effective. Indeed, rare diseases raise considerable equity questions, since 

they require a great amount of resources for a small group of people; this in turn means 

that said resources cannot be used where they may have had more effect on the overall 

health of the population. Therefore, it becomes essential for ERNs to become as efficient 

and  effective  as  possible,  in  order  to  compensate  for  the  opportunity  costs  that  they 

inevitably entail. As a side note, it can also be highlighted that cost effectiveness is also 

vital  for  the  long-term  sustainability  and  possible  expansion  of  ERNs,  given  that  their 

sources of funding are so scarce. 

Once these objectives have been agreed on, the second step is identifying how they can 

be  achieved  and, therefore,  which  aspects need  to be  evaluated to  define  a  network  as 

successful.  In this  sense, some  examples  can  be  drawn from  national networks  [3]  and 

from the experience of pilot ERNs [15], which have similar objectives and have focused on 

similar  issues.  For  simplicity,  we  will  follow  Donabedian's  well-known  structure-process-

outcome model, to have a clear framework in which to situate the actions undertaken. For 

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Application of the ERN model in European cross-border healthcare cooperation  

each  step,  we  will  briefly  summarize  the  specific  objectives  to  carry  out  and  indicate 

examples of how they have been applied to real-life situations. 

1. 

Structure: in the first place, it is necessary to clearly define what are the resources 

needed in reference centres and in the network for them to be able to deliver the highest 

quality of care and to carry out their role in the network. Obviously, these resources vary 

depending on the disease and therefore need to be defined on a case-by-case basis. Such 

resources can be broadly divided into: 

a. 

Equipment,  such  as  diagnostic  imaging  appliances,  or  laboratories  for 

genetic  testing.  One  particularly  important  requirement  is  the  presence  of  an 

information system and the information tools needed to get contact other experts, 

since one of the fundamental characteristics of ERNs is to allow knowledge to travel, 

rather than patients or physicians. To allow this to happen, the CPMS has been put 

in  place,  so  reference  centres  should  have  all  the  necessary  resources  to  use  it 

without difficulties. 

While  the  equipment  required  will  vary  according  to  the  subject  of  the  network,  an 

illustrative  example  is  from  the  Spanish  national  health  care  system,  where  providers 

aspiring  to  become  reference  centres  for  familial  cardiomyopathies  must  have,  for 

example: 

- 

Diagnostic  and  therapeutic  techniques:  250  echocardiograms,  50  cardiac 

MRI  scanners,  100  Holter  monitors,  100  units  to  conduct  exercise  stress  tests; 

capacity  to  perform  Pharmacologic  Induction  Tests  (flecainide,  procainamide  or 

adrenaline); and capacity to carry out Genetic Studies for the range of conditions 

included; 

- 

- 

Clinical consultations specially devoted to family cardiopathies. 

Other units/services: image diagnosis, echocardiograms and high quality MR 

Unit/Service;  unit  for  electrophysiology,  arrhythmias,  and  induction-unmasking 

techniques;  genetics  Service/Unit;  haemodynamic  Units  (diagnostic  and 

therapeutic procedures) including alcohol septal ablation; etc. 

b. 

Human resources, i.e. the professional expertise needed to deal with these 

difficult cases. 

Again, the Spanish health care system can give a fitting example with its reference centres 

for cardiomyopathies, where providers are required to have, for example: 

- 

Human  Resources:  2  cardiologists  dedicated  to  familial  cardiomyopathies; 

specialised nursing staff; 

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Application of the ERN model in European cross-border healthcare cooperation  

- 

Basic  training  for  the  members  of  the  team:  cardiologists  with  at  least  3 

years’  experience  in  familial  cardiomyopathies;  nursing  staff  with  more  than  2 

years’ experience in cardiology tests and familial mapping. 

c. 

Research  capacity,  i.e.  scientific  reputation  of  the  team  of  professionals 

involved  in  the  process  of  care,  with  reference  to  the  quantity  and  quality  of 

scientific production in the last 5 years. 

2. 

Process: this would probably be the aspect that can benefit the most from ERNs. 

Indeed,  most  have  focused  on  improving  it  by  concentrating  on  common  themes  and 

problems, which, according to the EUCERD report[15], are: 

a. 

Sharing  expertise  for  patient  management:  including  the  creation of tools 

for  case  management,  sharing  expertise  through  IT  media,  and  working  with 

patients and non-expert professionals to produce and disseminate. This is especially 

important  with  rare  diseases,  where  the  patients  themselves  often  know  more 

about  their  condition  than  the  physician,  potentially  creating  tensions  in  their 

relationship [16].  Consequently, the  type of  expertise  that  needs  to  be  shared  is 

not related  to  information  on the  disease,  but also to  the  ways  in  which  patients 

can be engaged respectfully and productively. 

The ERN for neurological diseases (ERN-RND) has published a very precise outline of its 

objectives, the specific goals each seeks to achieve, and the timing over which to achieve 

them [17]. Specific objectives for sharing of expertise include: 

- 

Define currently available education and training resources, by compiling a 

web  directory  of  currently  available  education  and  training  resources  for 

professionals/families, by month 12; 

- 

Establish an alert mechanism for rapid dissemination of new information, by 

establishing a list of high quality meetings/conferences and alert reports, by month 

36; 

- 

Identify  and  fulfil  patients'  and  professionals'  future  education/training 

needs in a survey of different stakeholders by month 12. 

b. 

Developing  standards  of  care:  this  includes  producing  best  practice 

guidelines  for  diagnosis  and  clinical  management  and  implementing  these 

guidelines and providing training in their use. 

Some examples from the ERN-RND include: 

- 

Evaluation of existing guidelines and pathways by a trained guideline expert 

group, with a priority list for new pathways and guidelines, by month 12; 

23 

 
Application of the ERN model in European cross-border healthcare cooperation  

- 

Improve  patient  care  through  use  of  high  quality  patient  guidelines,  by 

publication of a guideline list, by month 48; 

- 

Develop  cross-border  pathways,  by  a  framework  report  on  cross-border 

pathways, by month 60. 

c. 

A third aspect, not mentioned by the EUCERD report but that is nonetheless 

important,  is the  creation of  a  clinical  pathway  for  patient  management.  Indeed, 

the initial responses from the survey on integration [18] highlight how there is no 

agreed  referral  system  for  patients  inside  Member  States,  but  rather  it  is  left  to 

each physician to refer their patients. Therefore, it would be important to define a 

clear  process  through  which  patients  are  managed,  from  their  primary  care 

physician to highly specialized treatment, in order to optimise efficacy and efficiency 

at each step of care. 

Some examples from the ERN-RND include: 

- 

- 

- 

Consent and share diagnostic flowcharts, by month 12-60; 

Develop generic diagnostic pathway for genetically caused neurological diseases by 

month 36; 

Improve  access  to  high  quality  care  by  a  report  on  implemented  awareness 

strategies for ERN-RND, by month 12-60. 

d. 

In the process of care, networks could establish a system to share diagnostic 

and  therapeutic  processes,  by  providing  second  and/or  multiple  opinions  for 

patients taking advantage of information technology. 

3. 

Outcome:  finally, it  is necessary  for  the  networks to  find  a  way to  evaluate  their 

work, highlighting problems where they exist, but also documenting improvements brought 

about by the network. The main focus in this phase is on the objectives of the reference 

networks, namely: 

a. 

The provision of high quality care: networks should be able to provide better 

care  than  that  which  would  otherwise  be  available  to  the  patient.  This  can  be 

evaluated using outcome indicators, which need to be defined for each disease, but 

also patient reported outcome and experience measures. 

b. 

Equity in the provision of care: networks aim to ensure that all citizens are 

receiving  quality  care  based  on  need,  not  geographical  location,  social  status  or 

income. This could be considered by evaluating the level of awareness by physicians 

of networks  and  referral  processes,  or the  measures  put  in  place  by networks  to 

make themselves better known. 

24 

 
Application of the ERN model in European cross-border healthcare cooperation  

c. 

Cost-effectiveness  in  the  provision  of  care:  networks  should  ensure  that 

resources are being spent in a responsible and effective manner, in order to actually 

benefit patients and make the use of resources for rare diseases, rather than for 

more prevalent conditions, meaningful. This assessment is more complicated, since 

it raises moral issues (what is the level of effectiveness, which justifies the extra 

resources?), but one method could be confronting healthcare for patients with rare 

diseases before and after ERNs, in order to understand whether and how much it 

has improved. 

The framework that has been outlined in the previous paragraphs can be useful in agreeing 

criteria to define how effective a network is. The core belief behind it is that it is necessary 

to find practical, measurable aspects to understand how well a network is performing. A 

second  fundamental  aspect  is  to  make  the  entire  evaluation  process  as  public  and 

transparent as possible, as numerous experiences have shown how reputation, more than 

economic incentives, is a key factor in driving performance in the health care sector [19]. 

The question of what an effective network is, therefore, has no clear answer: it is necessary 

to establish its goals and, from them, derive the objectives to pursue. The achievement of 

these objectives needs to be evaluated with measures of outcome, and the result of this 

evaluation can then form the basis for the development of new objectives and measures, 

in what (hopefully) becomes a virtuous cycle. Therefore, this framework can be used when 

evaluating ERNs as well as any further application of them, in part or as a whole: clearly, 

however, if the ERN model were to be adapted to other realities, a new discussion on its 

objectives would be needed, leading to different indicators measuring its success.  

1.5. 

Are  there  other  areas  where  European  Reference  networks  might  be 
appropriate? 

One question that naturally arises when considering the results obtained by ERNs is: can 

a  similar  approach  be  used  to  tackle  other  healthcare  problems?  Can  it  be  extended  to 

other settings and to the treatment of other conditions? To answer these questions, first it 

is necessary to reflect on the reason for the creation of ERNs, the methods they have used, 

and whether there are sufficient similarities with other conditions to suggest that the ERN 

model might be appropriate. Second, it is necessary to ask if there is a case for considering 

the ERN model, whether there are alternative, more appropriate mechanisms to achieve 

the relevant goals. 

Fundamentally,  the  objective  behind  the  creation  of  ERNs  is  to  improve  healthcare  for 

patients  suffering  from  rare  diseases,  in  terms  of  quality  of  the  services  provided, 

efficiency, cost-effectiveness, and ease of access [20]. The need to resort to a European 

25 

 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

network, rather than implementing national measures in each country, has arisen because 

of  the  extreme  scarcity  of  cases:  it  is  very  difficult  to  provide  adequate  health  care  for 

complex  problems  when  there  are  extremely  few  patients,  as  is  the  case  especially  in 

smaller countries [16], [21]. Referral of all patients to a single network makes it possible 

to centralize knowledge and resources, and also accumulate a sufficient number of cases 

to  evaluate  outcomes  and  establish  best  practices  [15],  [22].  Indeed,  since  knowledge 

about rare diseases is scarce and continually evolving thanks to advances in research [23], 

one  of  the  main  activities  of  ERNs  is  the  sharing  of  knowledge  to  improve  treatment  of 

patients [15]. For patients, this translates into better quality of care and easier access to 

treatment, since patients can benefit from a team of experts without having to move to 

distant hospitals [24]. 

However, the goal of improving healthcare is hardly exclusive to ERNs, but rather is one 

of  the  main  objectives  of  all  national  health  systems.  Therefore,  it  is  legitimate  to  ask 

whether a similar approach can be useful in other circumstances or settings, to improve 

other features of healthcare. 

One  element  of  ERNs  is  the  exchange  of  knowledge  on  how  to  treat  certain  conditions. 

Without  a  structured  system,  such  as  that  created  by  the  ERNs,  it  is  difficult  to  know 

whether  different  centres  are  providing care  that is  consistent  with  best  practice,  to  the 

extent that this is known. In the absence of such a system, it is likely that there will be 

variation in models of care. This variation is not confined to rare diseases. It is widespread 

in  all  sectors  of  healthcare  with  unwarranted  variation,  i.e.  service  usage  differences 

among providers and regions that cannot be attributed to differences in patient needs or 

preferences but to other factors [25], [26]. These differences can be due to unequal access 

to services, disagreement about the best medical practice (although treatments that have 

been  proven  effective have  a  great  deal of regional  variation  as  well),  different  medical 

practice styles, or availability of resources [25]–[28]. These unwarranted forms of variation 

have a negative impact on the efficacy and efficiency of healthcare [29]: for example, they 

can indicate lack of conformity to clinical guidelines, a lack of equity in access to care, or 

a waste of money in ineffective procedures [27]. For these reasons, reducing unwarranted 

variation  is  a  priority  for healthcare  systems  as  they  pursue their objective  of  providing 

universal  and  equal  coverage  of  high  quality  [29].  Therefore,  going  back to the original 

question, one could ask whether the measures used by ERNs to solve the problems related 

to rare diseases can also be useful in addressing problems of geographical variation. 

The approach adopted by ERNs to address the issues related to care for rare diseases, as 

outlined above, is knowledge sharing and benchmarking. This implies that performance of 

the  healthcare  system  should  be  evaluated  in  a  transparent  and  systematic  manner  in 

26 

 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

order to identify areas of best practice and those which need to be improved on [30]. Then 

the  results  must  be  disclosed  to  the  public:  making  the  results  available  offers  the 

opportunity to share best practices and increases the physicians’ awareness of the quality 

of  their  performance  [31].  In  addition,  a  “reputation  effect”  [19]  is  set  in  motion, 

encouraging  professionals  to  take  steps,  where  feasible,  to  improve  their  performance 

[32], including advocating for a better use of resources, by investing them where they can 

yield better results (which means, in the case of ERNs, directing them towards international 

cooperation rather than towards less effective national care pathways). 

This  can  be  done  through  benchmarking,  i.e.  comparing  one’s  results  with  those  of  the 

best performer, learning how they are achieved, and applying the lessons learnt to improve 

[33]. These  actions  can lead to  a  significant improvement  in  both  quality  and  economic 

sustainability of healthcare [30]; in addition, they have been shown to improve equity by 

providing means to reduce unwarranted geographical variation [27].  

The question then is whether the ERN model might be appropriate as a means of reducing 

unwarranted variation, offering a forum in which those managing different conditions could 

share experience.  

We  do not  find this  argument  persuasive. Except in small  countries,  there is no obvious 

need to create an international network to function: on the contrary, there are reports of 

implementation of these measures at a local and regional level [26], [34], with excellent 

results even for common conditions, such as diabetic foot [30]. In other words, once there 

is  a  sufficient  number  of  cases,  the  methods  used  by  ERNs  can  be  easily  applied  at  a 

national, regional or even local level, since the focus is not on gathering information per 

se, but rather on using the information to improve healthcare, and increasing the amount 

of information available is useful only if it can change decisions on treatment. Indeed, the 

necessity  for  international  cooperation  has  only  arisen  for  rare  diseases  because  the 

volumes are too small to gather a reliable amount of data and identify differences in quality 

of care. Moreover, conditions with a higher prevalence can implement the same actions as 

ERNs  without  having  to  face  all  the  challenges  linked  to  international  cooperation  [11]. 

Even if there is a desire for international collaboration, for example to develop guidelines 

for complex conditions or indications for new treatments, this can often be achieved equally 

well by networks developed within other frameworks, for example by European scientific 

and professional organisations, many of which are already engaged in such mechanisms. 

While these activities can draw on the experiences from the ERNs in due course, they are 

substantially different: they are not defined by having a small number of cases, but rather 

by the fact that international cooperation would make tackling these issues much easier.  

27 

 
 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

A second issue is whether the ERN model can promote access to healthcare for vulnerable 

communities (such as cross-border communities that are currently not adequately covered 

by national health services), small countries, remote areas, and/or EU border regions, all 

of which may suffer from inadequate access to high-quality healthcare that is not limited 

to rare diseases. Again, there are many other mechanisms that can address these issues, 

including the now numerous examples of cross-border collaboration and it is not clear what 

the ERN model would add to them.  

There  have  also  been  several  proposals  to  create  ERNs  for  other  conditions,  issues,  or 

population groups. We now review some illustrative examples of these proposals.  

It has been suggested that it could be appropriate to create an ERN for humanitarian crises. 

However,  that  would,  to  some  extent,  duplicate  the  role  of  the  existing  European 

Emergency  Response  Capacity  and  the  European  Medical  Corps.  The  Panel  was  also 

informed  about  a  range  of  bilateral  and  multi-lateral  agreements  to  enhance  disaster 

preparedness, such as those to ensure access to hospital beds in neighbouring countries 

in  cases  of  earthquakes  other  disasters.  Thus,  there  are  many  alternative,  and  more 

appropriate mechanisms that can be employed other than an ERN. 

Another proposal is to create a network to improve the care of homeless people. Again, it 

is  not  clear  how  this  relates  to  the  ERN  concept.  Feantsa,  the  European  Federation  of 

national organisations working with the homeless, drew our attention to how, apart from 

Finland and Norway, all EEA countries have seen a rise in homelessness with, for example, 

a 150% increase in Germany from 2014 to 2016, a 20% rise in the number of people in 

emergency shelters in Spain of the same period and an 8% increase in Denmark between 

2015  and  2017  [35].  The  Panel  agrees  that  the  extreme  health  inequalities  homeless 

people face mean that homelessness is a health issue [36] and currently many health care 

systems across Europe are failing people who are homeless. However, the consequences 

of homelessness are likely to be highly context dependent, influenced by what services are 

available to homeless people and the pathways into and out of homelessness and it is not 

clear how the ERN would address this issue.  

Although all these initiatives have something in common, they are all related to problems 

of  rather  small  groups  in  the  European  Union  (e.g.  the  homeless  population  counts  for 

approximately 0.075% of the population at any given time in Europe), and in this sense 

there is a certain quantitative similarity with the situation of people with “rare diseases”, 

the  Panel  does  not  think  that  it  is  appropriate  to  copy  the  ERN  model  to  address  those 

needs. The European Reference Network-model is a strong “sui generis”-approach, suitable 

for patients with “rare diseases” as it concentrates expertise and knowledge, and acts as 

28 

 
 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

a super-specialised advisory level to improve diagnosis and treatment of people with those 

diseases.  

With other challenges (e.g. refugees, homeless people, disaster interventions) the needs 

of those affected should be addressed directly by offering appropriate service provision.  

That being said, the Panel urges Member States and the European Union to optimise the 

care  for  these  groups  and  the  preparedness  to  provide  acute  responses,  through  the 

creation of platforms and “Learning Communities” in Europe with participation of multiple 

Member States and experts in the different domains, in order to improve access in quality 

of  these  vulnerable  people.  This  action  certainly  relates  to  the  ambition  of  the  recently 

adopted  European  Pillar  of  Social  Rights.  Creating  these  platforms  and  “learning 

communities” around these topics, providing the needed evidence through practice-based 

research,  will enable health care  providers  in Europe to  better serve the  needs  of these 

vulnerable nations. In other words, there are many possible ways to share information and 

undertake action to tackle healthcare and social issues: rare diseases have been addressed 

using  the  ERN  framework,  while  other  problems  can  benefit  more  from  other  forms  of 

cooperation – and it is of the utmost importance that these communities and networks are 

put in place, in order to best deal with them. 

In  summary,  the  current  criteria  for  establishing  a  ERN,  as  a  means  of  improving  the 

management  of  patients  with  rare  and  complex  diseases,  was  appropriate.  The  ERN 

concept does not address other issues raised for consideration, such as remote areas and 

border regions, or the development of new medicines or interventions, for which there are 

alternative and more appropriate mechanisms. The Expert Panel was also asked about the 

scope  to  extend  the  scope  of  ERNs  to  other  areas  such  as  the  care  of  people  who  are 

homeless or emergency situations. In both cases, there are better alternative mechanisms 

to achieve the intended goals. However, the Panel does accept that improved responses 

are needed to meet the needs of homeless-people, refugees and other vulnerable groups, 

and  to  increase  preparedness  in  relation  to  disaster-interventions  through  specific 

“European Learning Communities”.  

1.6. 

Should the ERN model be used as a whole?  

The application of the ERN model as a whole or part of the model will depend on the needs 

to which the model is expected to respond. The ERN model can tackle one, several or all 

the main fields for action currently identified for rare diseases: research and innovation, 

generating and sharing evidence, developing guidelines, and training. 

29 

 
 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

Research is of paramount importance in the field of rare diseases, given how little is known 

about  them:  ERNs  should  bring  to  a  stronger  EU  research  governance,  based  on 

systematically identified research gaps and priorities [14]. In the field of rare diseases an 

example  is  the  EU  funded  project  RARE-Bestpractices  [37].  The  project  has  produced  a 

specific  resource  (RareGAP)  that  collates  validated  research  recommendations  for 

diagnosis and treatment of rare diseases, identified from high quality systematic reviews 

[38].  These  validated  research  recommendations  can  feed  the  research  agenda  on  rare 

diseases. 

In  a  similar  way,  an  active  cross-border  network  can  be  a  valuable  tool  to  pinpoint  the 

need  for  generating  new  evidence  also  for  conditions  other  than  rare  diseases. 

Consequently, it will be important to find a consistent way to feed the inputs of the ERNs, 

as research needs, into the EU research agenda. 

Clinical  guideline  development  can  be  highlighted  as  a  priority  topic.  In  fact,  Directive 

2011/24/EU [point (iii) of Act. 12(4)(a)], the Commission Delegated Decision 2014/286/EU 

and  the  Commission  Implementation  Decision  2014/287/EU  require  that  ERNs  and  the 

health  care  providers  wishing  to  join  ERNs  should  have  the  capacity  to  develop  and 

implement trustworthy clinical guidelines [20], [39], [40]. 

Production and implementation of clinical guidelines in the EU is far from satisfactory. Few 

countries have well-established systems in place, sustained by national or local regulations 

that provide mechanisms for quality assurance, implementation and use. Many countries 

still  rely  on  sporadic  initiatives  based  on  unclear  processes,  others  have  insufficient 

capacity for evidence-based guideline development or, even if they have the capacity, they 

lack a coordination of a central agency [41]. The ERNs offer an excellent opportunity (albeit 

not the only one) to (i) consider the importance of devoting resources to build an efficient 

system for developing and implementing guidelines, and (ii) ascertain the actual capacity 

of  healthcare  providers  to  produce  trustworthy  guidelines  according  to  international 

standards.  Since  ERNs  are  expected  to  pursue a  cooperative  approach  aimed  at  sharing 

expertise,  they  can  contribute  to  initiating  processes  to  establish  European  cooperation 

structures. This in turn can contribute to the production of clinical guidelines in accordance 

to robust international standards, leading to more equitable care across countries and a 

wider access for patients to care. 

However, it should be noted that the production of guidelines is hardly the only objective 

of ERNs, but rather it should be one of the end products of their activity. Indeed, clinical 

guidelines are known to be often ignored or misinterpreted, even in the case of the most 

common  diseases:  30-40%  of  patients  do  not  receive  effective  treatments,  while  up  to 

30 

 
 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

25% of them receive unnecessary or potentially harmful ones [42]. The varying degrees 

of  guideline  application  can  also  be  seen  when  examining  geographical  variation  in 

healthcare, of which it is a main determinant [27]. Because of this, guideline development 

and  dissemination  are  not  the  only  focus  of  ERNs,  but  rather  they  also  focus  on  other 

aspects of  rare  diseases  where  they  can make a  difference.  Conversely, there  are  other 

ways  to  highlight  the  importance  of  sharing  information  and  producing  valid  guidelines, 

without having to resort to ERN (such as highlighting unwarranted variation) [43]. 

Another characteristic of ERNs is the fact that training and e-learning are priority topics: 

the implementation of ERNs requires the availability of trained professionals at all levels of 

healthcare.  Therefore,  ERNs  might  be  focussed  on  up-to-date  training  of  healthcare 

professionals  across  EU,  possibly  in  conjunction  with  empowerment  of  patients  and 

citizens. 

Finally, a peculiar characteristic of ERNs, albeit one that has not been formally recognised, 

is the high  degree  of  patient involvement:  representatives of  patients  and their  families 

are members of the boards of ERNs [44] and patient advocacy groups participate in ERN 

activities  [24],  up  to  the  point  of  organising  publicity  campaigns  [10].  Because  of  this, 

another focus of the “ERN model” should be to further increase the participation of patients 

in  the  diagnostic,  treatment  and  follow-up  processes,  by  registering  and  sharing  their 

experiences,  thereby  improving  their  care.  This  can  be  facilitated  with  greater  use  of 

patient reported experience and outcome measures (PREMs and PROMs), already in use in 

various  national  health  systems  with  varying,  but  generally  good  outcomes  [45].  They 

would be especially useful in the field of rare diseases, since patients are highly involved 

in their healthcare [16] and can therefore give extremely important insights. 

In  summary,  while  it  is  not  possible  to  come  to  definitive  conclusions  about  the  role  of 

ERNs in we examined the scope of the ERNs research and guideline development, there 

would seem to be considerable scope for incorporating these additional roles beyond the 

immediate objective of providing advice on individual patients. This will, however, require 

dedicated resources, some of which will have to come from other sources. 

1.7. 

How should national health systems integrate such networks into their 

national framework?  

Properly implemented ERNs are not an obstacle to the overall functioning of the national 

healthcare systems; indeed, the added value of ERNs is evident as long as the focus is on 

information  and  knowledge  exchange  and  as  long  as  the  patient  is  only  treated  in  the 

“foreign”  system  when  it  is  appropriate  and  justified.  The  main  challenge  is  to  provide 

evidence of  the  added value of these networks  for  all  players, in  particular the  Member 

31 

 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

States. For the first time, Member States will not only cooperate with one or two others on 

the basis of framework agreements and using existing administrative arrangements, but 

with at least 8 Member States whose health systems differ. We need to identify and monitor 

indicators of relevance for the individual players, especially health authorities and insurers 

in Member States, in order to evaluate the entire process [46].  

The Expert Panel has consistently noted the importance of integrating ERNs within health 

systems of Member States, so as to ensure, as far as is possible, equity of access to the 

expertise they provide. This concern also featured prominently in the feedback on the draft 

of this report sent for public consultation. However, we must be absolutely clear that, while 

endorsing this goal, the diversity of systems within Member States makes it impossible to 

provide  detailed  guidelines  for  how  this  can  best  be  made  to  work.  Moreover,  as  the 

detailed  aspects  of  delivery  of  health  care  are  reserved  for  Member  States  under  the 

European  Treaties,  the  Commission  is  very  limited  in  what  it  can  do  except  to  facilitate 

sharing  of  good  practice.  Consequently,  it  will  be  important  to  include  this  issue  in 

monitoring of the implementation of the existing ERNs and taking steps to disseminate the 

lessons that arise from their experiences. 

The Expert Panel also noted that the ERNs do not seem to be well known in all Member 

States, among both relevant patient groups and health professionals. Although outside the 

remit of this opinion, there does seem to be a need for better dissemination of information 

by the ERNs about their activities.  

At this point it is important to consider the financial sustainability of the ERN model in the 

light of constraints facing some national health systems. At present, individual cross-border 

patient mobility takes place on a small scale. According to the May 2015 Eurobarometer, 

entitled “Patients’ rights in cross-border healthcare in the European Union”, only 5% of EU 

citizens  obtained  treatment  abroad  [46].  The  consequences  and  the  potential  financial 

burden associated with the establishment of the ERNs need further investigation and more 

time [46]. The optimal way to finance ERNs in the medium-long term remains unresolved: 

as  highlighted  above,  further  elaboration  will  be  needed  to  achieve  long-term 

sustainability. This issue may be a problem for all EU Member States, but especially so for 

some of them. 

A related issue is how continuing treatment can be provided for patients who benefit from 

the ERN system. The primary purpose of the ERN model is to provide expert guidance that 

can inform diagnosis and treatment. It is not to provide that treatment. Should a patient 

require treatment in another Member State, there are many mechanisms that can facilitate 

32 

 
 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

this, both through the Directive on Cross-order Care and numerous bilateral or multilateral 

arrangements. These existing arrangements could also be the basis for arrangements that 

draw on the concept of and lessons from ERNs, as could arrangements within some of the 

larger Member States, especially where expertise is concentrated in certain regions. Thus, 

the application of the ERN model does not need an EU dimension: it might be translated 

with equal or higher effectiveness to a national or regional framework [11]. 

The  feedback  to  the  consultation  on  our  draft  report  suggested  that  the  existing 

mechanisms for cross-border care are not well known or understood. Consequently, there 

may  be  a  case  for  providing  information  to  those  involved  in  ERNs  and  others  on  the 

arrangements  that  exist  within  cross-border  care.  It  will  also  be  important  for  those 

participating  in  ERNs  to  ensure  that  they  have  well-functioning  mechanisms  to 

communicate with their respective national focal points for cross border care.  

1.8. 

Proposed criteria for establishing ERNs 

In the light of the considerations described above, the Panel proposes a set of criteria for 

creating a European network. The Panel considered that four criteria were relevant: 

a)  The  condition/  intervention  must  be  rare  (however  defined).  The  Panel  saw  no 

justification  for  creating  a  pan-European  infrastructure  for  common  conditions 

where relevant expertise is widely available. 

b)  The condition must occur throughout large parts of the EU. Thus, a condition could 

be rare on account of its concentrating in a few families with a particular genetic 

anomaly but if they all lived in the same region then it is likely that expertise would 

also  be  concentrated  and  there  would  be  little  added  value  of  a  Europe-wide 

network. Similarly, if cases were concentrated in a few Member States, bilateral of 

multi-lateral  arrangements  might  be  more  appropriate.  There  may  be  some 

occasions in which a condition, especially infectious ones, that is not uncommon in 

some  Member  States,  such  as  tick-borne  encephalitis,  is  seen  in  travellers  who 

move  to  other  countries  where  it  is  not  endemic.  However,  again,  there  will  be 

alternative  mechanisms  available  and,  in  cases  such  as  this,  the  surveillance 

networks working with ECDC may be able to play a role.  

c)  The  condition  must  be  complex  and  there  must  be  incomplete  knowledge, 

benefitting  from  consultation  among  specialists.  A  condition  may  be  rare  but  its 

management may be straightforward and uncontentious. It would not justify a ERN 

model. 

33 

 
 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

d)  The establishment of a ERN should only be undertaken when there is no existing 

alternative  mechanism  to  obtain  access  to  relevant  expertise  or  other  forms  of 

collaboration or where a simpler solution is not possible. Such mechanisms exist for 

many of the topics suggested to us. 

CONCLUSIONS AND RECOMMENDATIONS 

ERNs  have  the  potential  to  facilitate  cooperation  at  the  EU  level  in  particular  medical 

domains with a focus on areas where expertise is scarce, facilitating access to diagnosis 

and  to  high-quality  health  care,  especially  in  the  area  of  rare  diseases.  As  such,  the 

establishment  of  ERNs  appears  to  have  been,  at  least  potentially,  among  the  most 

important European cooperative initiative for decades. 

ERNs seek to provide an important mechanism be powerful tools to support a consistent, 

up-to-date,  cost-effective  and  evidence-based  healthcare  for  those  with  rare  diseases 

across the EU. 

Potential  points  of  strength  of  the  ERN  model  include,  in  particular,  the  added  value  of 

knowledge sharing and the integration of the ERN system in the national health services 

of each Member State.  

The  ERN  model  stems  from  the  principle  of  subsidiarity  and  added  value  of  action  at 

European  level:  therefore, in  principle,  all those  healthcare  areas that  may  benefit  from 

cross–border  cooperation  could  be  interested,  including  those  caring  for  people  with 

complex, high-prevalence diseases, cross-border communities, and those facing increased 

health risks (homeless, refugees, etc.). On the other hand, ERNs for rare diseases have 

been implemented for only one year. This is too short a time in which to make an evaluation 

of  outcomes,  costs  and  points  for  improvement.  Moreover,  there  is  a  wide  range  of 

alternative  and  more  appropriate  mechanisms  for  dealing  with  many  of  these  issues, 

including care in border areas and vulnerable populations.  

ERN financing in the medium-long term is also a health policy issue; further elaboration 

may  be  needed to  optimize the  long-term  sustainability of ERN.  The  sustainability issue 

may  be  a  problem  for  all  EU  Member  States,  but  especially  for  some.  Moreover,  ERNs 

require extended cooperation among at least 8 Member States, whose health systems can 

be very different, making such cooperation challenging to achieve. 

However, properly implemented ERNs are not an obstacle to the overall functioning of the 

national healthcare systems; indeed, the  added  value of ERNs  is  evident  as long  as  the 

34 

 
 
 
 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

focus  is  on  information  and  knowledge  exchange.  The  main  key  challenge  is  to  provide 

evidence, by means of adequate indicators, of the added value of these networks for all 

players, in particular the Member States.  

Based on the above considerations, the extension of the ERN model to diseases other than 

rare diseases is considered premature. 

More data are required on benefits and costs of ERN for rare diseases, in order to achieve 

a  more  robust  body  of  evidence  to  support  the  extension  of  the  model  to  other  health 

conditions. Such conditions likely have features that would call for adaptations of the ERN 

model currently implemented for rare diseases: such features include (but are necessarily 

limited to) relatively high frequency, multifactorial aetiology, multiple clinical phenotypes 

under  the  same  diagnostic  umbrella  and  multiple,  sometimes  divergent,  approaches  to 

diagnosis and treatment. 

The application of the ERN model as a whole or part of the model will depend on the needs 

to which the model is expected to respond in fields other than rare diseases. Therefore, 

the ERN model can tackle one, several or all the main fields for action currently identified 

for rare diseases: developing guidelines, training, research and innovation, generating and 

sharing  evidence.  Clinical  guideline  development can  be  a  priority topic  as  requested  by 

the Directive 2011/24/EU. Indeed, the development [47], production and implementation 

[48]  of  clinical  guidelines  in  the  EU  is  far  from  satisfactory.  ERNs  can  support  initiating 

processes to establish European structures of cooperation in producing guidelines, pursued 

through  structured  knowledge  sharing;  this  could  lead  to  more  equitable  care  across 

countries  and  a  wider  access  for  patients  to  care,  including  either  rare  and  frequent 

conditions. 

In addition, an active cross-border network can be a good means to pinpoint the needs for 

generating new evidence; it will be important to find a consistent way to feed the lessons 

from ERNs into the EU research agenda. 

It is recommended that well-designed, independent research is carried out on the impact 

of  ERN  on  healthcare  of  rare  diseases  including  the  clinical  (e.g.,  improved  diagnosis), 

scientific (e.g., added value of shared knowledge) and social (e.g., benefits for patient’s 

life quality, sustainability) aspects [20]; the adaptations that may be needed in order to 

fit the ERN model to diseases other than rare diseases. 

Finally,  the  implementation  of  ERN,  for  rare  diseases  as  well  as  for  other  conditions, 

requires the availability of trained professionals at all levels of healthcare; it is, therefore, 

35 

 
 
 
 
 
 
Application of the ERN model in European cross-border healthcare cooperation  

recommended that  the  lessons learned  from ERNs  should  be  reported  and  disseminated  

in ways that can feed into in the undergraduate through to post-graduate and professional 

education of the healthcare professions. 

36 

 
 
Application of the ERN model in European cross-border healthcare cooperation  

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40 

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