Plan For Rare Diseases Research Articles

Recommendations for Centres of Expertise in Rare Anaemias. The ENERCA White Book

The Community added value of Centres of Expertise (CoE) and European Reference Networks (ERN) is particularly high for rare diseases (RD) due to the rarity of these conditions, which implies both a small number of patients and scarcity of expertise within a single country. Gathering expertise at the European level is therefore, paramount in order to ensure equal access to accurate information, appropriate and timely diagnosis and high quality clinical care and follow up for patients with rare diseases. This applies particularly to rare anaemias due to the high number of different rare diseases that constitute this group. In this context, the European Network for Rare and Congenital Anaemias (ENERCA), co-financed by the European Commission, was created in 2002 with the aim of prevention and management of rare anaemias (RA) and the development and promotion of policies to improve the well-being of European Union citizens. The ENERCA White Book is a position paper, developed as a deliverable of the ENERCA (phase 3) project that intends to contribute to the creation of a ERN in RA (ERN-RA) by preparation of the recommendations and, in particular, the definition of the criteria that CoE, local centres (LC) and their interrelations have to fulfil as healthcare providers. It has been nourished by all the activities that have been performed over the past ten years within the ENERCA framework. The White Book is addressed to authorities in charge of the identifying CoE, as an essential requirement for the official recognition of the ERN, to European and national health authorities, Healthcare centres and health professionals, as well as to all other stakeholders interested in RA. It is also addressed to the patients, as a way to empower their community in this process. One particular characteristic of the White Book is the integration of the three main aspects of a CoE: (a) ethical and legal frameworks to ensure the non-discrimination and non-stigmatisation of rare disease patients across Europe, within their sphere of competencies; (b) clinical and laboratory frameworks for defining technical and quality criteria including scope, general and disease specific elements currently defined as technical and professional standards for the diagnosis, treatment and follow-up of patients with RA; and (c) the expectations patients have of CoE. Conceived as a working tool directed to a broad range of stakeholders, the White book has been designed and structured to be comprehensible even to non-technical and /or non-professional audiences. The reader will find an up-to-date description and epidemiological information on RA as well as the European Union background policies for defining CoE and ERN-RA. A working group was created with experts of different profiles, known as the European Working Group on Rare Anaemias (EGRA). In order to achieve its objectives, the methodology used by EGRA, was characterised by three main principles: Interdisciplinary, European coverage, and evidence-based principles. Work has been developed into four sequential steps: 1. Analysis of the current situation of RA in Europe by healthcare professionals in order to identify the most relevant issues that have to be addressed by a centre in order for it to be recommended as CoE. 2. Preparation of questionnaires to perform surveys on how the relevant issues identified in step 1 can be translated into practical recommendations. 3. Analysis of the questionnaire results by face to face meetings, feedback and consensus evaluation, and 4. Preparation of a report on ENERCA policy recommendations for CoE. This report is presented in a user-friendly format, easy to understand and available through the ENERCA website (www.enerca.org). Several important conclusions can be drawn from the ENERCA White Book, including the importance of laboratories involved in the diagnosis of RA, patient oriented and multidisciplinary care at the CoE, the need for coordination and cooperation within and outside the centre, the provision of information to patients and health professionals and the involvement of public authorities at the national and European levels. Official recognition of this structure and assurance of its long term sustainability will only be achieved if public authorities work hand by hand with both professionals experts in different disciplines and patients. Finally, the ENERCA White book aims to be a practical tool for health authorities of Member States (MS) that are preparing their national directory of formally designated CoE. For this, it is important that MS authorities recognise RA as an important health component to be included within the National Plans or Actions for Rare Diseases.

Rare diseases and orphan drugs: Latvian story.

BackgroundTen years have passed since Latvia became a Member State of the EU in 2004. As a result European regulations, including those related to rare diseases and orphan drugs, have been applied to Latvian legislative system. Orphan diseases have been recognized as a priority area for action in the public health system, though there are significant differences in the national healthcare services for rare diseases among the EU States. This study aims to determine situation in the field of rare diseases in Latvia and compare it with other European countries.MethodsWe used the national plan for rare diseases, EUCERD reports, Orphanet data, Latvian and European regulations, publicly available data from the state agencies, and directly contacted drug manufacturers and wholesalers.ResultsNational plan for rare diseases was developed and approved in 2013. Although there are no official designated centers of expertise as well as no specific register for rare diseases. Newborns are screened for only two disorders: phenylketonuria and congenital hypothyroidism. Currently 34 orphan drugs are available on Latvian market. Three medicines (8.8%) are included in the reimbursement drug list, all indicated for Ph + CML. 15 drugs (44.1%) were reimbursed within the framework of individual reimbursement system, and five drugs (14.7%) were provided within the program of medicinal treatment of rare diseases in children.ConclusionsMajority of orphan drugs authorized in the EU are not available in Latvia, moreover those drugs that are available are often not accessible because they are insufficiently reimbursed. Besides, approval of the national plan might be an important step towards improving situation in the field of rare diseases.

Prenatal counselling and the role of the paediatric surgeon

With the development of prenatal ultrasound and of foetal medicine, the paediatric surgeon has extended his knowledge of the natural history of surgical malformations. He is a part of the prenatal team and parents should always be referred to him when a surgical malformation is suspected, even when termination of pregnancy is planned because of an expected poor prognosis. Direct contact between the prenatal medicine specialist and the paediatric surgeon is also highly recommended to ensure continuity in the messages delivered to the parents. Postnatal counselling does not compare with prenatal counselling, and the paediatric surgeon has learned from the obstetrician to modulate his talk by including other conditions that might affect the outcome of the foetus, especially genetically determined syndromes. When the foetal malformation is diagnosed very early, especially in the first trimester, it therefore seems important for the consultation with the paediatric surgeon to be scheduled when the complementary exams required by the anomalies diagnosed are done, in order to avoid later contradictory messages. Repeated consultations should be favoured as they allow provision of more precise information regarding changes in ultrasound and/or MRI images and so decrease parents׳ anxiety and help them to take their decision. Foetal surgery, which has reached various stages of development in different countries, requires paediatric surgeons and obstetricians to join forces to optimise procedures and evaluate their benefit/risk ratio. Since 2004, the National Rare Disease Plan in France has allowed the creation of Rare Disease Centres, which deal with congenital malformations and produce recommendations for the health care pathway of these patients by means of a multidisciplinary approach. This greatly enhances interdisciplinary communication and ensures that best care is provided to the parents-to-be and to their child.

The Creation Of The National Registry Of Rare Diseases In The Slovak Republic

Abstract The creation of a registry of patients with rare diseases is a priority of the National Strategy for Rare Diseases as well as of the National Plan for Rare Diseases. Knowledge of the real number of patients with rare diseases would thus, in addition to basic clinical information, represent an important point in planning health and social care. The presented work introduces points of departure which constitute the basis of a new specific National Registry of Patients with Rare Diseases in the Slovak Republic. Its creation builds on the existing registries as well as on the structure of health care in the Slovak Republic. With the protection of personal data in mind, the collection of data will be carried out by the National Centre of Health Information (NCHI), which will also use the existing tool in the process of creation. Thanks to the cooperation between NCHI and the Slovak Society of Medical Genetics, NCHI developed separate reporting forms on rare diseases according to OMIM (Online Mendelian Inheritance in Man) and ORPHANET rare disease coding (ORPHA codes of rare diseases), and the International classification of diseases code (ICD 10). The activities also include cooperation with the existing registries (part of which are rare diseases). For example National Registry of Congenital Developmental Heart Defects, national register of neuromuscular disorders, oncologic register or register of diabetes mellitus. Gathering the information from these registries we will extend the data about rare diseases in the Slovak republic. At the international level the participation in the European Surveillance of Congenital Anomalies (EUROCAT) is important.

A methodology for a minimum data set for rare diseases to support national centers of excellence for healthcare and research.

Although rare disease patients make up approximately 6-8% of all patients in Europe, it is often difficult to find the necessary expertise for diagnosis and care and the patient numbers needed for rare disease research. The second French National Plan for Rare Diseases highlighted the necessity for better care coordination and epidemiology for rare diseases. A clinical data standard for normalization and exchange of rare disease patient data was proposed. The original methodology used to build the French national minimum data set (F-MDS-RD) common to the 131 expert rare disease centers is presented. To encourage consensus at a national level for homogeneous data collection at the point of care for rare disease patients, we first identified four national expert groups. We reviewed the scientific literature for rare disease common data elements (CDEs) in order to build the first version of the F-MDS-RD. The French rare disease expert centers validated the data elements (DEs). The resulting F-MDS-RD was reviewed and approved by the National Plan Strategic Committee. It was then represented in an HL7 electronic format to maximize interoperability with electronic health records. The F-MDS-RD is composed of 58 DEs in six categories: patient, family history, encounter, condition, medication, and questionnaire. It is HL7 compatible and can use various ontologies for diagnosis or sign encoding. The F-MDS-RD was aligned with other CDE initiatives for rare diseases, thus facilitating potential interconnections between rare disease registries. The French F-MDS-RD was defined through national consensus. It can foster better care coordination and facilitate determining rare disease patients' eligibility for research studies, trials, or cohorts. Since other countries will need to develop their own standards for rare disease data collection, they might benefit from the methods presented here.

Diagnosis and management of idiopathic pulmonary fibrosis: French practical guidelines.

Idiopathic pulmonary fibrosis (IPF) is the most frequent chronic idiopathic interstitial pneumonia in adults. The management of rare diseases in France has been organised by a national plan for rare diseases, which endorsed a network of expert centres for rare diseases throughout France. This article is an overview of the executive summary of the French guidelines for the management of IPF, an initiative that emanated from the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. This review aims at providing pulmonologists with a document that: 1) combines the current available evidence; 2) reviews practical modalities of diagnosis and management of IPF; and 3) is adapted to everyday medical practice. The French practical guidelines result from the combined efforts of a coordination committee, a writing committee and a multidisciplinary review panel, following recommendations from the Haute Autorité de Santé. All recommendations included in this article received at least 90% agreement by the reviewing panel. Herein, we summarise the main conclusions and practical recommendations of the French guidelines.

200th ENMC International Workshop “European Reference Networks: Recommendations and Criteria in the Neuromuscular field”, 18–20 October 2013, Naarden, the Netherlands

200th ENMC International Workshop “European Reference Networks: Recommendations and Criteria in the Neuromuscular field”, 18–20 October 2013, Naarden, the Netherlands

Ritka Betegségek Nemzeti Terve

The rarity of low prevalence diseases and the lack of information, research, diagnosis, treatment and expert availability may mean that the people affected do not benefit from the health resources and services they need. Rare diseases are considered to have little impact on society as a whole, yet they pose serious difficulties for sufferers and their families. By the end of the last century, two robust achievements in science and technology, i.e. the biotechnological and informatics revolutions, have created a real base for global approach to rare diseases by coordinating the capacities for health care, biomedical research and drug development and pooling the very limited resources available both nationally and transnationally. The European Commission has taken a number of actions which help patients and professionals to share expertise and information across borders with the objective of reducing the number of people suffering from these types of diseases. These actions together form the legal basis of the European Union policy on rare diseases. Orphan or rare diseases are now one of the priorities in the public health programmes in European Union. In 2009, the document "European Union Council Recommendation on an action in the field of rare diseases" was released with the main goal to provide national health authorities with supporting tools for the development and implementation of national plans and strategies for rare diseases by the end of 2013. This recommendation adopted by European Union Member States, allows common policy guidelines to be shared everywhere in Europe. By September 2013 the Hungarian National Plan for Rare Diseases, a health policy strategy until 2020 was finalized. The present report gives a short view on the document.

Evolution of national and European policies in the field of rare diseases and their impact over the past five years

The 2009 Council Recommendation on an Action in the Field of Rare Diseases (2009/C 151/02) [1] encouraged Member States to elaborate a national plan or strategy for rare diseases before the end of 2013. One of the principal tasks of the European Union Committee of Experts on Rare Diseases (EUCERD) [2], through its Scientific Secretariat, was to analyse the results of the actions cited in the Recommendation, notably through the production of the annual report on the ‘State of the Art of Rare Disease Activities in Europe’ [3]. The 2014 edition of the report considers the impact of European policy and national plans/strategies (Figure ​(Figure1)1) on the organisation of health care and services for patients with rare diseases, including access to diagnosis and treatment, as well as considering progress in the field of registries, rare disease research initiatives, the genetic testing offer, access to information on rare diseases, patient organisations, and specialised social services. In terms of national plans and strategies for rare diseases, by end 2013, the deadline to elaborate national plans/strategies for rare diseases fixed by the Council Recommendation, most EU Member States had submitted a plan/strategy to their national authorities and sixteen countries have adopted a plan/strategy (Figure ​(Figure2).2). France and Spain have implemented and assessed their first plan. As their number one priority, most countries plan to identify and design centres of expertise for rare diseases. Many of these plans/strategies, however, have no dedicated budget for their actions, a result of the unfavourable economic context which may hinder the implementation of defined measures. The next challenge for EU Member States will be to effectively implement and assess these plans, which the new Commission Expert Group on Rare Diseases [4] will follow closely. Research in the field of rare diseases has been boosted in recent years due to European and international initiatives, such as European research projects funded via the DG Research and Innovation framework programmes and the E-Rare ERA-NET [5] as well as the creation of the International Rare Disease Research Consortium (IRDIRC) [6]. The Orphanet database [7] continues to expand and provides data collected in 37 European and surrounding countries with partner teams in Canada and Australia and negotiations ongoing in other world regions. Nearly all countries now have a national alliance for rare diseases ensuring that the voice of rare diseases, carried by Eurordis [8] at the European level, is heard. Figure 1 Emergence of concepts and initiatives surrounding rare diseases in Europe (December 2013) Figure 2 Stages of development of national plans or strategies for rare diseases in EU MS in December 2013

The French national registry for rare diseases: an integrated model from care to epidemiology and research

The first national plan for rare diseases (2005-2008) set the network for care and research in the rare diseases (RD) field across all French hospitals. The 131 RD centers of expertise (CE) initiated then various IT projects to register electronically their RD patients. The CEMARA project [1] up to now registered 235,000 RD patients, from 62 RDCE (out of 131), 383 units of care and described over 4000 rare diseases. The identified limits of the CEMARA model were: i) data collection was not incorporated in the care setting, ii) exposed to data re-entry, iii) coping with data privacy new regulations and iv) gaining a wide national consensus on the data to collect for all RDs and from all CEs. To overcome these limits, the 2nd national plan for rare diseases (2010-2014) promoted the creation of a national data repository for all rare diseases (BNDMR) based on the CEMARA model with the following objectives: i) identifying RD patients within the health information systems in care setting, ii) describing the RD demand of care, and the adequacy of the supply and iii) identifying patients eligible for clinical trials or cohorts. The proposed national architecture incorporates a national minimum data set for all rare diseases (F-MDS-RD) into hospital information care systems to enable electronic patient files re-use for epidemiological studies or research [2]. To ensure a full interoperability between local hospital information systems and the BNDMR, a national interoperability framework is defined. It is set on 3 pillars: i) defining a national patient ID for rare diseases that will help to identify patients across different health IS, ii) defining a common data format for all rare diseases, compatible with EHR standards such as HL7, and iii) setting the necessary technical data flows complying with strict security rules for data privacy [3] and security. The minimum data set for rare diseases is now being implemented in several local systems, and connectors are being rolled out with several database suppliers. Data re-entry is nowadays a major concern for clinicians. Enabling data re-use is not only an interoperability problem; data must be structured, qualified, standardized [4] and suitable for research [5]. The structuration of the data collected is set on a variety of standard terminologies such as Orphanet or the Human Phenotype Ontology which requires to be accompanied with the necessary IT tools to help clinicians coding the data [6].

Emergency guidelines and emergency cards

Rare diseases are not well known by physicians acting in emergency departments, and taking care of RD patients in the emergency setting can prove challenging for them. Emergency situations can result from the rare disease itself or be unrelated to it, but most often need particular measures to be taken. In order to guide the emergency practitioner in a very practical way to take care of a patient with a diagnosis of a rare disease, a collection of emergency guidelines is being developed by Orphanet. They are produced by French reference centres for rare diseases and reviewed by emergency practitioners. Patient organizations are also involved in their production so as to make sure that relevant non-medical aspects of care are taken into account. Emergency guidelines are organized in two sections dedicated to the pre-hospital setting and to the hospital emergency department respectively. So far more than 50 guidelines are available in French and are being translated and adapted in other European languages. They have been downloaded more than 340,000 times in 2013 from the Orphanet website (http://www.orpha.net). They are also available in the Orphanet mobile application (developed for iOS and Android), in order to allow emergency practitioners to have timely information in the pre-hospital setting. Besides of emergency guidelines, the French Ministry of Health has produced personal emergency cards for a number of rare diseases during the first national plan for rare diseases. These cards include summarized recommendations in case of emergency intended to physicians, as well as relevant personal information to be completed by a practitioner in the centre of reference. It includes some recommendations for patients intended to prevent emergency situations related to the disease. Emergency cards are also available on the Orphanet website.

Welsh plan for rare diseases

Welsh plan for rare diseases

Rare diseases and referral centers

Rare diseases represent a major public health challenge due to their number, presently estimated to be between 6000 and 8000, their severity and the absence of any preventive treatment. The enactment of two National Plans for Rare Diseases by the establishment of Referral Centers and Diagnosis and Treatment Centers has brought about a recognition of the specificity of these disorders, the creation of a epidemiological database, a framework for rapid diagnosis protocols at the first symptoms, greater access to specialized care to accompany the afflicted and their families during their frequently difficult medico-social journey, training of skilled health professionals in the field of these rare diseases, promotion of basic and clinical research and finally the development of European partnerships in both research and therapeutic planning.

Evaluation of Centres: the French experience since 2009

The first French National Rare Disease Plan allowed the establishment of 131 centres of expertise (CEs) from 2004 to 2007. The process of evaluation elaborated with the HAS (Haute Autorite de Sante) was based on a cycle of 5 years: three years after the certification, the CEs were asked for a document of auto-evaluation and at 5 years there was a visit on site to complete the evaluation. As the certification of CEs was done over a period of 4 years, all the CEs were not evaluated at the same time and it resulted in a complex scheme with heterogeneity of the evaluation according to the time point of the process. The items collected during autoevaluation consisted in general information regarding the composition of the team and of the steering committee, the methods used for the elaboration of the document and quantitative data concerning the activities (clinics, hospitalizations, geographical origin of the patients, proportion of children). Six specific missions of the CEs were also evaluated: expertise, referral, research, epidemiology, healthcare pathway and medicosocial organization. The documented ended with an action plan on which the experts relied for their evaluation during the visit on site at 5 years. This process demonstrated many positive aspects: constructive stimulation of the actors, commitment of institution direction and set up of a virtuous circle based on the fundamental three steps: anticipation, implementation and evaluation. However this process had many caveats: redundancy of some items that led to confusion in the responses, lack of support for the methodology mandatory to evaluate the impact of the CEs actions, heaviness of the organisation of the visit on site and most of all impossibility to retrieve essential information and to analyse them as the documents were elaborated on a word file with free text. The evaluation of the first plan by the high council of public health thus concluded it was necessary to simplify and to optimize the efficiency of the process. In addition, it has to take into account the new ambitions of the 2nd plan. A working group dedicated to this question collaborated with the HAS and elaborated a simplified document for certification. The process now includes an on-line simplified annual activity report based on quantitative and semi-quantitative data. These reports will be analysed each year by a permanent group – with adjustment of the financial support- together with a final report at 4 years based on the new certification document. Visit on site will be decided only if problems appear during this follow-up or on request of the centre.

Esophageal atresia: Data from a national cohort

PurposeA prospective national register was established in 2008 to record all new cases of live-birth newborns with esophageal atresia (EA). This epidemiological survey was recommended as part of a national rare diseases plan. MethodsAll 38 national centers treating EA participated by completing for each patient at first discharge a questionnaire validated by a national committee of experts. Data were centralized by the national reference center for esophageal anomalies. Quantitative and qualitative analyses were performed, with P-values of less than 0.05 considered statistically significant. Results of the 2008–2009 data collection are presented in this report. ResultsThree hundred seven new living cases of EA were recorded between January 1, 2008, and December 31, 2009. The male/female sex ratio was 1.3, and the live-birth prevalence of EA was 1.8 per 10,000 births. Major characteristics were comparable to those reported in the literature. Survival was 95%, and no correlation with caseload was noted. ConclusionsEpidemiologic surveys of congenital anomalies such as EA, which is a rare disease, provide valuable data for public health authorities and fulfill one important mission of reference centers. When compared with previous epidemiological data, this national population-based registry suggests that the incidence of EA remains stable.

Epidemiology of esophageal atresia

Esophageal atresia (EA) is a rare congenital malformation consisting of a lack of continuity between the upper and lower esophageal pouches, frequently associated with tracheoesophageal fistula. The prevalence of such rare abnormalities is established by global birth surveillance programs over the world. EUROCAT is a European program covering 1.7 million births since its creation. The prevalence of EA in Europe seems stable over decades. The National Birth Defects Prevention Network in the USA also shows a stable prevalence with a wide range between states or regions. In France, with the implementation of the national rare diseases plan, a reference center for congenital abnormalities of the esophagus was created in 2006 and a national registry for EA began patient inclusion in 2008. This has resulted in the establishment of the national live birth prevalence for EA, prenatal diagnosis rates, and clinical characteristics of EA patients, early survival, and early morbidity. Prevalence rates seem stable all over the world since many decades. Continuous surveillance of congenital abnormalities and specific registries are useful for epidemiologic data but also for public health authorities for helping families of rare diseases patients.

National plans: case study Belgium

In October 2011 the Belgian Fund for Rare Diseases and Orphan Drugs, a consortium of stakeholders supported by the King Baudouin Foundation, handed over the recommendations and proposed measures for a Belgian Plan for Rare Diseases. In follow-up of the EU recommendations to issue national plans by 2013, the Minister of Public Health and Social Affairs commissioned the Fund to propose a comprehensive plan. The proposals cover 11 action domains, among them patient empowerment, improving access to treatment, ethics and governance. 42 measures have been proposed and a budgetary estimate was issued. Realising the plan would necessitate a 17 million euro investment over a 5 year period and an additional yearly expenditure of 44 million euro: compared to the national health Insurance budget of 25 billion euro, this seems a limited effort to realise! Still, adding expenditure to the budget under actual pressure to curb down health expenditure growth rates is not evident. Although governmental endorsement of a national plan has not yet taken place, most probably due to the economic and budgetary context, several measures have been launched by the Minister. These measures pertain to the core of action to be taken: setting up a national registry for rare diseases, disclosing information through Orphanet in national languages, developing centers of expertise based upon international guidelines, recommendations and guidance through Eucerd, adapting procedures in order to make early temporary reimbursement possible.

Spina Bifida and primary prevention

Spina Bifida is a neural tube defect (NTD), which occurs within the first 25 days of pregnancy and affects around 1 in 1000 pregnancies in Europe. It cannot be cured, although improved medical interventions mean that many people with Spina Bifida live into old age and have a good quality of life. However lifelong follow-up is required. IF is an umbrella organisation of national organisations of persons with Spina Bifida and focuses on primary prevention, access to health and the right to life. Around 70% of Spina Bifida can be prevented by a daily intake of Folic Acid two months prior to conception and two after. With Folic Acid the same child is born without Spina Bifida. Access to life-saving treatment of new-borns with Spina Bifida is in discussion. IF strives for the right of treatment of all new-borns with Spina Bifida. Spina Bifida became a rare disease because of prenatal detection and terminations of pregnancies and not because of primary prevention. Several hospitals closed their coordinated care units for Spina Bifida. Research decreased and Spina Bifida is perceived by many professionals as a solved problem. Prevention of most of the birth defects starts before conception. That's why IF co-organised in October 2010 a European Preconception Care conference in Brussels. When a couple plans their pregnancy they should take all measures to prevent possible problems: not drinking alcohol, not smoking, not taking drugs and taking Folic Acid. IF advocates for fortification of staple food with Folic Acid and set up a European awareness campaign. Most women do not know about the risk of having a baby affected by an NTDs. This is even truer among women of lower socio-economic status where the incidence is higher. IF produced two reports on Prevention of NTD's in Europe and organised a hearing in the European Parliament. To improve peri-conceptional folate levels women of childbearing age can only be reached by a combination of counselling, intake of Folic Acid, fortified staple food and further investment in monitoring and research. Persons with Spina Bifida make the need for prevention visible and IF believes that it should be integrated in National Plans for rare diseases. In Belgium we had a first success. A crucial orphan drug in the care for the neurogenic bladder is taken for approval.

The need for worldwide policy and action plans for rare diseases

There are more than 6000 rare diseases (defined as affecting <5/10 000 individuals in Europe, <200 000 people in the United States). The rarity can create problems including: difficulties in obtaining timely, accurate diagnoses; lack of experienced healthcare providers; useful, reliable and timely information may be hard to find; research activities are less common; developing new medicines may not be economically feasible; treatments are sometimes very expensive; and in developing countries, the problems are compounded by other resource limitations. Emphasis is required to support appropriate research and development leading to better prevention, diagnosis and treatments of rare diseases. Notably, clinical trials using already existing drugs may result in new, affordable, treatment strategies. Moreover, rare diseases may teach us about common disorders.ConclusionsCountries are encouraged to implement specific research and development activities within their individual capabilities, so that patients worldwide have equal access to necessary interventions to maximize the potential of every individual.

Professional clinical guidelines for rare diseases: methodology

Guidelines are systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances[1]. They concern often complex diagnostic or therapeutic strategies with several possible interventions at each step, where each intervention has to be assessed and compared with other possible interventions at short and long term for efficacy, effectiveness, efficiency (optional), side effects, quality of life, acceptability, benefits/risks ratio. For common diseases, the methodology and the different steps of the guidelines development process have been established and apply the principles of evidence-based-medicine. Developing guidelines for rare diseases (RD) is more difficult, because of the lack of sound evidence, surveys of clinical practices, data about patients’ opinion and ethical reflexions [2]. During the 1st French national plan for rare diseases, HAS (French National Authority for Health) was mandated to define a method to develop guidelines for RD - which are called PNDS (National Diagnostic and Treatment Protocols) in France - and coordinate their writing with the RD centres of reference [3]. A PNDS constitutes a best practice reference document for healthcare professionals in charge of rare disease patients. Based on it, HAS drawn up a “List of Procedures and Services” (LAP), which includes all of the diagnostic tests, drugs, medical devices and services that appear justified in providing care to a patient. From 2005 to now, only 47 PNDS were published and 8 are on-going, because the development method is complex and expertise is scarce; 135 new PNDS projects are pending. In the 2nd French plan for rare diseases it was proposed to define a simplified method for developing the PNDSs, in order to speed up their production, by using the protocols already developed by the RD reference centres, incorporating and adapting recommendations devised by foreign groups of experts when appropriate; and setting criteria for prioritisation of the PNDS production. This process is on its way. Orphanet has launched the production of emergency guidelines, written by centres of reference in collaboration with emergency department practitioners, patient organisations, and validated by a special reading group with members of emergency medicine learned societies. They include a short description of the disease, recommendations for immediate care, transport and orientation, before getting to the emergency ward, recommendations for the emergency ward (complications to be looked for, diagnostic and therapeutic particularities, drugs interactions, anaesthesia), recommendations for patient’s and family’s comfort, list of contacts 24h/24 [4].