Rare diseases within United Europe

First of all, is there a particular reason for you to be involved in rare diseases activities? When did you first “face” the rare diseases topics?
AK: I have been in this role for about 20 years. I joined Genetic Alliance UK because I was interested in the way in which new scientific possibilities influenced our opportunities to improve the circumstances of people living with serious, chronic and life limiting conditions. My younger daughter has a treatable auto-immune disease so we have family experience of the importance of bio-medical research and the translation of the outcomes of this into effective products. Rare diseases have been a constant thread in this work. When I started, medical genetics was all about rare conditions. Today, advances in research are showing us that common conditions – at least on the surface – are really clusters of rare disorders underneath with sometimes very different genetic elements that require different interventions and therapies. Perhaps there will not be common diseases for much longer as they break up into clusters of genetically distinct subsets!
AM: I have a personal motivation. I face for the first time topics to mortality and morbidity related to rare diseases in 2001 when I was responsible in Eurostat on some areas of health statistics. When I take new responsibilities in DG SANCO in 2003, rare diseases were a secondary topic but very quick it becomes a major topic in the activities of the European Commission in the field of public health.
DM: In 1998 I have been invited, as scientist working at the Italian National Institute of Health by the Italian Minister of Health to participate to a meeting organized between patients and families with rare diseases, scientists and health authorities.

You have been a longtime actor in rare diseases field. What has changed now on European level in comparison to when you started working on these problems?
AK: I think the most significant change is the growing recognition that rare is not the same as uncommon, and that there is a need to address the issues generated by the impact of rare diseases strategically and on a public health basis rather than as a series of individual tragedies that, whilst distressing to the patient affected are too few to get the attention of planners and policy makers.
AM: The first European initiative in the field of rare diseases was the Decision No 1295/1999/EC of the European Parliament and of the Council adopting a programme of Community action on rare diseases within the framework for action in the field of public health (1999 to 2003). This was not a real programme of action but a funding instrument giving to the different stakeholders the first opportunity to create EU collaborations and networks (the database Orphanet constitutes the best example). In 2000 the Commission adopted the Regulation (EC) No 141/2000 of the European Parliament and of the Council on orphan medicinal products which introduced for the first time a European definition on rare diseases, any disease having a prevalence of less than 5 per 10 000 of population, but obviously focusing on incentives to pharma companies to research and develop drugs not having economic return. At the same time the Framework Programme on research, FP5, launched also initiatives on rare diseases research very significant in terms of impact. During these years before 1999 still end 2003 the different actions of the EU lacked of a public health orientation and appropriate coordination. Things started to change in 2004 after adoption of the First European Public Health Programme (2003-2007) and the Sixth Framework Programme (2003-2007). Rare diseases become a strategical objective in the EU public health and research policies and consultative structures, at EU level, were created for the first time. The EU Task Force on Rare Diseases was created in 2004 and has given a significant input to the EU in terms of impulse and help to refine European cooperation in the field of rare diseases. In 2008 the European Commission decided to adopt the Commission Communication to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions on Rare Diseases: Europe’s challenges and to propose to the Council the adoption, finally done in 2009, of the Council Recommendation on an action in the field of rare diseases. After adoption of both documents the EU had, finally, a coherent framework of activities shared by the European Commission and the Member States. The adoption of the Commission Decision of 30th November 2009, establishing a European Union Committee of Experts on Rare Diseases, permitted to create a large structure where al  the stakeholders (Member States, Patient’s organisations, Industry, Research community, Public Health projects, etc.) are represented. Also the fact that the most part of recent legal initiatives in the EU in the field of public health takes into account explicitly the interest of the rare diseases patients becomes an excellent new (e.g. Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the application of patients’ rights in cross-border healthcare, etc.).
DM: It has changed a lot in terms of EU public health actions as well as in research. Since 2008 rare diseases are a priority area for action in Public Health Programmes. Considering rare diseases as a whole, and not singularly, helped highlighting and recognizing a series of healthcare problems and planning focused public health actions involving groups of population with common needs, safeguarding at the same time their peculiarities and differences. Communication of the European Commission “Rare Diseases: Europe’s challenge” and “Council Recommendation on a European action in the field of rare diseases” allowed common policy guidelines to be shared everywhere in Europe. The adoption of the Commission Communication (2008), and of the Council Recommendation (2009), and the Directive on Cross-border healthcare have created an operational framework to act in the field of rare disease with European coordination in several areas (national plans o strategies, classification and codification, European Reference Networks, orphan drugs, European Committee of Experts, etc.). Many Countries adopted actions to tackle rare diseases in order to improve prevention, early diagnosis and appropriate treatments. In the field of research the EU Commission has launched many initiatives starting with the different Framework programs (FP) where many projects on rare diseases have been funded to last international initiative the International Rare Diseases Research Consortium (IRDiRC). Maximising scarce resources and coordinating research efforts are key elements for success in the rare diseases field. Worldwide sharing of information, data and samples to boost research is currently hampered by the absence of an exhaustive rare disease classification, standard terms of reference and common ontologies, as well as harmonized regulatory requirements. In conclusion, it is no doubt that EU integration and cohesion policies have greatly contributed to make rare diseases issues more visible and more comprehensible throughout Europe.

What are you most satisfied of the recent advances in this area?
AK: Advances have occurred in several areas. Firstly, advances in our understanding of the basic biology of a growing number of rare diseases are creating insights that will allow us to make progress towards interventions and treatments that will improve the control of symptoms and perhaps one day allow us to produce cures or to prevent these conditions from developing. The second area of improvement has been in the adoption of legislation that helps to create a framework for sustaining research and development and generating specialist knowledge in the care and support needed by patients and families. For example, the Orphan Medicinal Products Regulations have provided a huge stimulus to the development of treatments for rare diseases, and the recently adopted Cross Border Health Care Directive should (it’s early days yet) support the development of centres of expertise with the critical mass to really improve services and support for families. This directive ought to facilitate the movement of patients to centres where they can receive high quality treatment not available closer to home. Whether it does remains to be seen, and patient groups will need to be vigilant to secure the rights of their members to access this high quality support if national health care systems are reluctant to pay for it.
AM: The situation has certainly changed very positively from 2004 and specially 2008. I think everybody should be proud about the enormous advances in the visibility and knowledge of rare diseases in the EU policy. I’m specially satisfied with the consolidation of the database Orphanet as the rare diseases world reference in the field, the increasing role that the EU policy has given to patient’s organisations, and specially EURORDIS, as key players in the EU policy, the recommendation to Member States to adopt a national plan on rare diseases before the end of 2013 and with the legal definition in the EU Cross-border healthcare Directive of the need to create European Reference Networks.
DT: All the initiatives described above have been very important although with different weight.

Rare diseases are a unique sphere where European cooperation and consensus are crucial to move things forward. What’s the way to find an effective balance between the interests of so many different groups of interactors?
AK: I think that the key to success is to try and adopt a collaborative approach with other key stakeholders. Patient groups have a unique role in promoting the interests of their members, and we must not allow this purpose to be compromised. However working with others who have overlapping interests, be they doctors, researchers, industry, policy makers or whoever, to help them understand that, by meeting patient expectations they will be able to do a better job themselves will enable us to lever their resources and insights towards the pursuit of a common goal. Of course we must reserve the right to be confrontational when others are doing things that run counter to patients’ interests, but confrontation should be a last resort, not the first tool out of the box.
AM: The specificities of rare diseases – limited number of patients and scarcity of relevant knowledge and expertise – single them out as a unique domain of very high European added-value. There is probably no other area in health where collaboration between 27 different national approaches can be as efficient and effective. Coordination at EU level is probably the best way of pooling the very limited resources available. However no EU policy on rare diseases is possible without an active cooperation with national authorities and stakeholders. This was the sense of the creation of the European Union Committee of Experts on Rare Diseases (EUCERD). This Committee will assist the Commission in formulating and implementing the Community’s activities in the field of rare diseases, and shall foster exchanges of relevant experience, policies and practices between the Member States and the various parties involved as well as to assist the Commission in the monitoring, evaluating and disseminating the results of measures taken at Community and national level in the field of rare diseases. It should also contribute to the implementation of Community actions in the field, in particular by analysing the results and suggesting improvements to the measures taken and deliver opinions, recommendations or submit reports to the Commission either at the latter’s request or on its own initiative.
DT: We should always keep in mind that the benefit of patients and their families are the central core of initiatives and efforts made by Institutions, patient organizations, scientists, industries, etc. at EU and national level. Transparency, especially regarding funding, among different players should be ensured.

People do not always understand the difference between the EU level approach to rare diseases issues and the specific actions, taken by the individual countries. How EU policy decisions should be transferred into national authorities’ actions, so we could have better results?
AK: In my experience a twin track approach is often the best way forward, and an early start helps to prepare the ground. When EU approaches are under development those who will be responsible for implementing them at national level need to be engaged with at as early a stage in the process to discuss what the implications might be and how the benefits might be realized. Practical and realistic options based on the opportunities on the ground in the Member State need to be worked out, remembering that what works in one country may not in another. Enlist the support of key allies – clinicians and others will want to take advantage of opportunities to help their patients, but they can only do this if they know about them, and try and secure a seat at the tables where decisions are being made. At the same time, it is important to work on awareness amongst politicians and the wider community by advocacy on behalf of patients in Parliament and in the policy forums where legislation is laid down that will transpose EU initiatives into national law, and through intelligent use of the media to generate public support that can be translated into political pressure thereby making a positive outcome more likely.
AM: As mentioned before, Member States should adopt a national plan or strategy in the field of rare diseases before the end of 2013. The content of these national plans/strategies should have a double dimension. From one side a National Plan or Strategy can be defined (EUROPLAN Definition) as a set of integrated and comprehensive health and social policy actions for rare diseases (with a previous analysis of needs and resources), to be developed and implemented at national level, and characterised by identified objectives to be achieved within a specified timeframe. On the other the content of these national plans/strategies should include and implement the EU recommendations and should define the international and European operation as a regular and normal way to proceed in order to obtain sustainability, efficiency and appropriate use of resources.
DT: Increasing the debate with national governmental institutions. In this respect EUCERD has an important role, especially through the active participation of national members.

What’s the added value at-large of the EU funded projects and initiatives, such as EUROPLAN, EPIRARE, RD Portal, etc.?
AK: These projects help to create a critical mass of shared experience and expertise that maximize the chances of making progress together and reduce the chances of people re-inventing the wheel and wasting scarce resources in the process.
AM: To improve information, identification and knowledge on rare diseases in order to obtain better diagnosis and treatment cannot be done, in any field, by a single Member State. The projects you pointed out are a clear example of international cooperation in fields in whit a high European added value has been obtained in describing and promoting high quality information on available services and actions as well in creating an international cooperation to improve classification and codification of rare diseases (Orphanet), in promoting synergies and common quality criteria for rare diseases registration (EPIRARE) or to provide technical assistance and recommendations to establish national plans/strategies for rare diseases (EUROPLAN). In all the cases there are achievements impossible to obtain o a single and isolated national action.
DT: The added value of EU funded projects and initiatives is enormous. Let me just give you few examples of my own experience.
EUROPLAN is to promote and implement National Plans or Strategies to tackle rare diseases, to share relevant experiences within Countries, linking national efforts with a common strategy at European level. This “double-level” approach ensures that progress is globally coherent and follows common orientations throughout Europe. EUROPLAN I has elaborated agreed tools for the development and implementation of National Plans following the Council Recommendation. Its contuniation, EUROPLAN II, is to establish an international and interactive network of stakeholders (mainly policy makers) to speed up the elaboration and the implementation of Rare Diseases National Plans, trough scientific and technical assistance, and the active participation of patients. EUROPLAN has really increased the capacity building of participants, has supported Countries with different geographical and economical concerns and different states of readiness for plan delivery by sharing experiences, disseminating successful practices. Finally, it has also identified feasible EUROPLAN indicators to monitor progress of different rare diseases activities.
EPIRARE is a project, motivated by the increasing interest of researchers in the establishment of disease registries. The need for shared quality data collections for different health and healthcare purposes and the awareness of difficulties posed by their maintenance is witnessed by a number of recent documents. The recent adoption of the Council Recommendation on RDs, which recommends the development of registers and databases for epidemiological purposes, is expected to result in a burst of initiatives for RD registration. While a wide population base is especially needed for epidemiological and clinical research in RDs, the Regulation on personal data protection creates important challenges to EU data collection and exchange, requiring a legitimate purpose for health data collection. It is therefore urgent to set up a common regulatory, ethical and technical framework to avoid that spontaneous initiatives in EU Countries find sound but autonomous solutions and legal bases, resulting in a waste of time, resources and health. EPIRARE aims to carry out a feasibility study addressing regulatory, ethical and technical issues associated with the registration of RD patients and with the creation of a EU platform for the collection of data on RD patients and their communication among qualified users. Possibilities for long-term sustainability of registration in the platform will also be studied by seeking synergies among different interests like research, health technology assessment, management of healthcare and policy purposes. To this aim, the project will define options for the preparation of a legal basis, fields in which effective synergies can be achieved, governance framework and possible options to support the platform.

It is no doubt that EU integration and cohesion policies have greatly contributed to make rare diseases issues more visible and more comprehensible throughout Europe. Nevertheless, a lot of problems still exist. In your opinion, what is now the biggest challenge in rare diseases field in EU?
AK: I think the economic climate represents a major challenge to sustaining the progress we have made to date, and to continuing to improve services and support for rare disease patients. Downward financial pressures on health care systems are already resulting in cutbacks in many countries. There is a real threat that the artificial conflation of “rare” with “insignificant” will threaten services for rare disease patients disproportionately as funders try and cope with budgetary pressures, and rare disease specific services are often seen as expensive in terms of the cost per patient treated. We must resist this trend vigorously.
AM: Sustainability of existing and future actions in the field of rare diseases constitutes the main challenge for the coming years. The existing financial instruments in the ongoing EU programmes (Health Programme, FP7, etc.) not guarantee this sustainability. The future EU programmes to be adopted for the period 2014-2019 (Health fro Growth Programme, Horizon 2020) should includes this sustainability dimension. Public opinion should not forget that the budgetary authorities in the European Union are the European Parliament and the Council.
DT: All countries should have rare diseases on their political agenda and therefore they should start or continue policies followed by concrete actions. However, we know that this is not the case for many countries. There is no doubt that the role of the EU Commission is crucial through its initiatives and actions which will be reflected at national level. EUCERD has an enormous importance in this respect; the involvement of all Countries (of course following the democratic rules) in the EUCERD Bureau will give responsibility and opportunities to all.

In Eastern Europe we often say that solving rare diseases problems is rather a question of changing the stakeholders’ mind and attitude than designing particular policies. What’s your experience tells about it?
AK: I think perceptions are important. When rare diseases are seen as a whole then they become visible, and the need to act collectively and strategically becomes apparent to the health care system. Of course, individual rare diseases may require some specific interventions, but there is a commonality that can be created by clustering and the systematic use of scarce expertise through the development of centres of expertise. These can be real or virtual, and there must be imaginative use of novel ways of working such as e-medicine to bring this about. The first step though is to define the issue in a way that those with access to power, influence and resources can understand, and then see a way to address. Until this happens there is a risk that the needs of rare disease patients will be lost in the fog of competing demands on the time and attention of policymakers and the professional community.
AM: This is something valid in Eastern Countries or in Western Countries. It is estimated that between 6 000 and 8 000 distinct rare diseases exist today (currently 5 860 are described in the Orphanet database), affecting between 6% and 8% of the population in total. In other words, between 27 and 36 million people in the European Union are affected by a rare disease. If rare diseases should become a public health priority this should be the result of a change of mind in public health authorities that the European Commission promotes and support. A public health problem affecting 6-8% of the European population should be a priority in all the countries.
DT: I have the same experience in my Country, however I have also to underlay that specific policies such as National Plan or Strategy dedicated to rare diseases are needed to embed initiatives and actions in the health systems.

What’s your message to “Rare Diseases & Orphan Drugs” readers?
AK: In the last twenty years we have made significant progress. Research has generated insights into a growing number of rare diseases that could not have been imagined only a few years ago, and a growing number of conditions that were formerly life limiting are now treatable. However the vast majority of rare diseases remain poorly understood, and there is a long way to go before the needs of all rare disease patients can be properly met. We need to work together as patients to support each other in the pursuit of this shared goal, recognizing that solidarity will be a driver for progress. Together we can make a difference where separately we lack the voice to make ourselves heard in the corridors of power. Make doctors, scientists and politicians our allies on this journey. They want to do a good job too. Help them to see that, by listening to the patient voice and responding to it, their task will be made easier and we will all benefit as a result.
AM: Rare diseases constitutes an unique example of European added value and a privileged field for international cooperation but this is only feasible if the need of the European and international cooperation is understood by all the stakeholders everywhere.
DT: Unity is strength. Therefore, let’s continue and reinforce the collaboration among all different stakeholders, inside the same country and among all countries.