EUROPEAN COMMISSION Brussels, 25.4.2018 SWD(2018) 126 final COMMISSION STAFF WORKING DOCUMENT Accompanying the document COMMUNICATION FROM THE COMMISSION TO THE EUROPEAN PARLIAMENT, THE COUNCIL, THE EUROPEAN ECONOMIC AND SOCIAL COMMITTEE AND THE COMMITTEE OF THE REGIONS on enabling the digital transformation of health and care in the Digital Single Market; empowering citizens and building a healthier society

{COM(2018) 233 final}



Contents 1. Introduction 1.1. Policy Context 1.2. State of Play 1.3. New Developments and Challenges 1.3.1. Citizens' access to personal data concerning health 1.3.2. Cross-border access to data for research and personalised medicine 1.3.3. Security of communication infrastructure and networks 2. Citizen's secure access to electronic health records and the possibility to share health data across borders 2.1. Electronic Health Record (EHR) and digital access to personal health data 2.2. State of Play 2.2.1. Lack of Electronic Health Records (EHR) interoperability 2.2.2. Citizens' access to EHRs and cross-border exchange of health data amongst professionals 2.3. Remaining challenges at the EU-level 3. Better data to advance research, disease prevention and personalised medicine 3.1. Fragmented data and computing capacity 3.2. State of Play

3.2.1. Digital infrastructure to support research and personalised medicine 3.2.2. National and international initiatives on personalised medicine 3.2.3. Initial areas of application 3.3. Remaining challenges at the EU-level 4. Digital tools for citizen empowerment and person-centred care 4.1. Challenges for health systems and the strive for affordable innovative solutions 4.1.1. Coping with an epidemic of chronic conditions 4.1.2. People at the heart of reformed health and social care models 4.1.3 The role of digital solutions 4.2. State of Play 4.2.1 Relevant initiatives and evidence 4.2.2. Low uptake of digital health from pilot to large-scale deployment 4.2.3 Market fragmentation and challenges to European enterprises integrating innovations into the health and care systems 4.2.4 From start-up to scale-up 4.2.5. Lack of strategic approaches to investments 4.3. Remaining challenges at the EU-level



1. Introduction

1.1.Policy Context Europe faces a major challenge with the sustainability and quality of healthcare provision, as a consequence of demographic change, increased longevity and rising prevalence of chronic conditions. Public expenditure on health and long-term care has been increasing over the last decades in all EU Member States, and is expected to rise even further. In 2015, it accounted for 8.5% of GDP in the EU and could reach up to 12.5% of GDP in 2060. Despite increased spending in health and long-term care, and advances in medical science, those extra years of life gained through increased longevity are not necessarily spent in good health. Healthy life years indicate the amount of life spent in a healthy state, rather than the length of life, and are an important measure of the relative health and quality of life of populations. Between 2010 and 2014, there have been virtually no gains in healthy life years in many EU countries. This suggests that greater efforts may be needed to prevent illness and disability and to improve the management of chronic conditions to reduce their disabling effects. The Commission Communication on effective, accessible and resilient health systems concluded that Member States’ future ability to provide high quality care to all will depend on making health systems more resilient, more capable of coping with the challenges that lie ahead. And they must achieve this while remaining cost-effective and fiscally sustainable. These needs have been recognised by policy makers,. In particular, the Council Conclusions on the Economic Policy Committee - Commission Joint Report on health care and long-term care in the EU identified a number of reform measures to address policy challenges in health and long-term care systems, including: strengthening health promotion and disease prevention; moving healthcare out of the hospital sector towards more cost-effective primary and ambulatory care services; and promoting integrated care. Innovative solutions that make use of digital technologies can, if designed purposefully and implemented in a cost-effective way, provide the means to support such reform measures in health and long-term care systems. eHealth, telemedicine and other digital technologies such as 4G/5G mobile communications, artificial intelligence and supercomputing offer new opportunities to transform healthcare systems. They allow the capture, management and processing of large volumes of diverse data generated from multiple sources to create new knowledge. They enable new approaches to personalised medicine, accelerating scientific progress, early diagnosis and prevention of diseases and more effective treatments. Furthermore, digital tools can assist in addressing shortages in health and care staff in rural areas and certain specialties. They can also connect the various actors across the health and social care sectors, thus ensuring effective sharing of data and collaboration, in more effective care models. In addition, digital technologies can enable citizens to access information about health risk factors and well-being measures, and help them engage in healthy lifestyle behaviour and disease prevention. Finally, the analysis of digital health data and patient-reported data can lead to improved procedures, reduce inefficiencies, support outcome-oriented healthcare, promote the evidence-based assessment of innovative health technologies, as well as improve emergency preparedness and response to epidemics. EU policies have consistently emphasised the importance of digital solutions such as eHealth. The afore-mentioned Communication on effective, accessible and resilient health systems and the Annual Growth Survey 2016 stress how digital innovations can improve integration of care through up to date information channels and deliver more targeted, personalised, effective and efficient healthcare, reducing errors and length of hospitalisation. Furthermore, the Directive on patients’ rights in cross-border care identifies specific areas where Member State co-operation in eHealth can bring significant added value to national health systems, such as in the cross-border exchange of patient summaries and use of ePrescriptions, and for clinical professionals through the European Reference Networks. Finally, making full use of the possibilities of digitalisation is one of the policy options identified in the Joint Report on Health Care and Long-Term Care Systems and Fiscal Sustainability. While the 2015 Digital Single Market Strategy for Europe (DSM) did not focus specifically on digital health and care, there were several references to eHealth. These references mentioned the digital health sector as an example (amongst other sectors) where digital services could bring benefits to citizens and businesses. The Communication highlighted in particular the need to make progress on standardisation and interoperability of digital solutions in the health sector supporting health systems' reforms. In response to the Digital Single Market Strategy, work focused on the major identified areas, including those in the digitising industry and public services initiative of April 2016 (specifically in the ICT priority standardisation plan and the eGovernment action plan). 1.2. State of Play In May 2017 the Commission Communication on the mid-term review of the Digital Single Market suggested to increase coordination efforts on the digital transformation of health and care in Europe, focusing on three priorities: (i) Citizens´ secure access to electronic health records and the possibility to share it across borders and the use of ePrescriptions, (ii) Supporting data infrastructure, to advance research, disease prevention and personalised health and care in key areas including rare, infectious and complex diseases (iii) Facilitating feedback and interaction between patients and healthcare providers, to support prevention and citizen empowerment as well as quality and patient-centred care, focussing on chronic diseases and on a better understanding of the outcomes of healthcare systems. Other areas of law or policy initiatives are directly relevant for the development of a Digital Single Market for health and care. They include the protection of personal data, interoperability and research and innovation funding. The protection of personal data The General Data Protection Regulation (GDPR) applicable from 25 May 2018 will provide a uniform set of rules for data protection across the EU. The GDPR has direct relevance for the digitalisation of health, and Article 9 (processing of special categories of personal data) defines particular provisions that apply to health data. The General Data Protection Regulation allows Member States to maintain or introduce further conditions, including limitations, with regard to the processing of genetic data, biometric data or data concerning health (Article 9.4). It is to be noted that Recital 53 of the General Data Protection Regulation states that this should not hamper the free flow of personal data within the Union when those conditions apply to cross-border processing of such data. After the adoption of the General Data Protection Regulation the Commission has established an expert group with the mission to clarify how Member States' existing and future legislation will ensure effective and uniform application of the General Data Protection Regulation. Under the General Data Protection Regulation the drawing up of codes of conduct is to be encouraged to contribute to the proper application of the Regulation, taking account of the specific features of the various processing sectors. The Biobanking and BioMolecular resources Research Infrastructure - European Research Infrastructure Consortium (BBMRI-ERIC), the Commission-supported pan-European distributed research infrastructure, has launched a roadmap process for the preparation of a code of conduct for life sciences and health research. This builds on the Code of Practice drafted by the projects funded by the Innovative Medicines Initiative (IMI). Interoperability Cross-border interoperability and access to health data among Member States and between national healthcare systems are supported by different EU instruments that are currently implemented, such as the Directive 2011/24/EU on the application of patients’ rights in cross-border healthcare among Member States.

The 2008 Commission Recommendation on cross-border interoperability of electronic health record systems has been adopted as a follow-up to the eHealth Action Plan which, in 2004, defined interoperability of electronic health records as one of the priorities for Member States. The Recommendation was intended to support the premise that connecting people, systems and services is vital for the provision of good healthcare in Europe insofar as it is necessary to enable the free flow of patients as well as digital health products and services, and hence may contribute significantly to the establishment and functioning of the internal market. A refined eHealth European Interoperability Framework (ReEIF) was adopted by the eHealth Network in November 2015. The ReEIF provides a common framework of terms and methodologies that aims to address eHealth interoperability issues and serve as a key instrument for the improvement of projects and solutions in the particular domain. Moreover, a new European Interoperability Framework (EIF) was adopted on 23 March 2017 in the context of the implementation of the Interoperability Solutions for European Public Administrations (ISA²) programme (2016-2020). The new EIF is meant to be a generic interoperability framework that could be used for the alignment of existing, or the creation of new, domain-specific interoperability frameworks (DIFs) such as those that could be developed in the field of electronic health records and other digital health applications. However, the framework alone does not provide technical specifications. Other relevant policy areas The EU provides targeted research and innovation funding under Horizon 2020 supporting the use of digital technologies in health and long-term care services and the implementation of the Digital Single Market strategy, including a roadmap for standardisation, harmonisation and interoperability supporting sustainable market development for the use of digital technologies in health and care services. Other actions relevant for future initiatives on the digital transformation of health and social care include the work pursued by the eHealth Network and investment commitments in digital health and social care from national and regional authorities working under the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Member States' existing and future legislation regarding the processing of data that concerns health may affect access to data across borders and the advancement of research and personalised medicine. The 2008 Commission Recommendation on cross-border interoperability of electronic health record systems and subsequent work carried out in the development of the European Interoperability Framework for eHealth (ReEIF) have so far been insufficient to deliver cross-border access to electronic health records by healthcare professionals, or to ensure that citizens have the technical means to access and manage their personal health data. Despite the significant investments made in this area by the EU, Member States and regional authorities, the uptake of digital innovation for health and care remains slow and varies greatly amongst Member States and regions. 1.3. New developments and challenges Notwithstanding the considerable potential of digital technology to contribute to better health and care outcomes, and the cross-border dimension of digital health products and services, the European Union is not a fully functioning single market for digital health and care solutions. Most citizens are unable to access their health data both within their own country as well as across borders, national initiatives to gather data to support personalised medicine remain fragmented (and small-scale) across Europe and digital solutions are successfully implemented in pilot settings but consistently fail to scale up. Below are some of the issues that effectively or potentially affect the realisation of a digital single market for health and care. 1.3.1. Citizens' access to personal data concerning health Digital technologies (e.g. smartphones, tablets, wireless sensors, etc.) that can be employed in mobile health (mHealth) surveillance, prevention, and intervention efforts have become more affordable and easy to use. These solutions can help citizens and professionals address preventable risk factors associated with chronic diseases (e.g. unhealthy diet and physical inactivity). They can also support active and healthy ageing, and facilitate early detection of symptoms and timely treatment, thus reducing the need for more burdensome treatments later on. Digital solutions that empower citizens with access to their personal health data are central to support a shift in health and care provision. They allow the citizen to be actively engaged in prevention of chronic conditions (active and healthy ageing), adherence to treatments and providing feedback on the quality of health and care. However, the citizens' ability to access their personal health data remains differentiated across and within Member States. It ranges from non-existent in some, partial in others, to full access in certain Member States. Often the personal data concerning the health of a given citizen is scattered across different local and national data repositories (e.g. hospital, primary care, others). A recent report adopted by the eHealth Network provides a snapshot of the current state of play of patient access to their electronic health records in the EU: -Nine countries have implemented systems at a national level that provide patients with online access to their eHealth data for some time now. What patients can access can be quite narrow e.g. health information only (Hungary), patient summary only (Finland). -Seven countries stated that they had national level electronic health record projects that included patient access to electronic health record information in development. -Ten countries stated that they provide access to patients to their eHealth data through multiple regional, local or speciality systems. Of this group, nine countries described current projects to develop a national system with patient access functionality, and the Netherlands are preparing guidelines for the development of regional systems that provide patients access to electronic health record data. The three countries that selected ‘No electronic health record systems’ (Cyprus, Czech Republic, Ireland) are planning to provide patient access to eHealth data ‘within 2 years’, ‘within 4 years’, and ‘in 5 years or more’ respectively. Malta has an online portal for doctors and their patients that fulfils much of the functions of a national electronic health record in terms of patient access to electronic health record information, but is also planning a national project to begin within 2-4 years.

Health system reforms aim at a shift from a hospital-centred system to more home and community-based, person-centred and integrated care structures. Portals that provide citizens with access to their personal health data, are an important enabler of this shift. But these portals are far from being the norm across the EU. Whilst several Member States have launched initiatives to create national patient portals these initiatives are not currently coordinated at EU level in a way that would encourage cross-border interoperability and secure cross-border access to electronic health records by authorised healthcare professionals. 1.3.2. Cross-border access to data for research and personalised medicine Over the last years there has been an extraordinary increase in the amount and quality of health data generated by new devices and technologies. At the same time, improvements in computing capacity and performance and the emergence of other digital technologies that allow large data storage and advanced data analytics make it possible to accelerate research and development of new treatments, as well as prevention and early diagnosis of diseases. It is widely shared among the stakeholders that access to varied data-sets located across different Member States remains difficult or inexistent, the data is subject to different taxonomies and standards and therefore scientific research invariably builds on relatively limited population cohorts. Larger scale cannot be achieved without cross border secure access to data sets, a shared computing and storage capacity and an appropriate regulatory framework that allows for secure access to data-sets across borders. Without these, it is increasingly difficult for healthcare organisations to optimise the quality and efficiency of their services and for EU researchers to achieve the critical scientific breakthroughs needed to support early diagnosis of diseases, enable coordinated response to epidemics or accelerate therapy development cycles across Europe. An element highlighted by stakeholders as being important to enable the pooling of health data for research at EU level will be to proactively ensure that the national laws adopted by Member States to further specify the General Data Protection Regulation with respect to research and processing of health data will not result in further fragmentation of the single market. Lack of coordination among Member States in that respect could potentially result in major barriers for achieving the required critical mass of data that is necessary to succeed in providing personalised medicine solutions for European health systems and citizens. In this context, effective coordination among Member States regarding the potential use of new emerging solutions can play an important role, if implemented systematically across Europe as part of the national and EU-level data and computation infrastructures for personalised medicine. These solutions must comply with the General Data Protection Regulation and could build on trusted distributed data ledgers (such as blockchain) for giving access to personal health data. Conversely, the absence of coordinated actions, and fragmented approaches to cybersecurity solutions, could potentially make it increasingly difficult for health data to be pooled at EU level to support medical research and personalised medicine. Several stakeholders in the research community have raised concerns with the potential effects of lack of coordination amongst Member States in the development of their national laws in the area of health and research that could result in the establishment of widely varying safeguards, conditions and applicable derogations and could negatively impact the establishment of the European Research Area. Such developments could also undermine investments in initiatives such as the European Open Science Cloud, which will rely on secure cross-border flows of data. Stakeholders representing the research community and patients' organisations have called for effective cooperation mechanisms between Member States and a minimum set of security requirements to ensure an equivalent level of protection of personal data shared by patients for healthcare and research purposes across the European Union, and to facilitate cross-border healthcare and research. Furthermore, experts in the scientific and medical research community particularly involved in cancer research have consistently underlined that the individual right to data protection should not harm the population's right to health and urged the Member States to ensure that the possibility to maintain or introduce further conditions regarding health data conferred upon them by the new Regulation would not only make cancer research possible, but also as effective as possible. 1.3.3. Security of communication infrastructure and networks Secure information and communication technology (ICT) infrastructures and data networks are critical to support the free flow of health data across borders in a secure and trusted environment. Healthcare organisations, like other regulated industries, have increased efforts to maximise security measures to protect their own infrastructure and data networks. According to recent research, healthcare data security incidents ranked second for the services industry in 2016. In addition to the General Data Protection Regulation, which introduces security requirements applicable also to healthcare organisations, the European Commission is also working to assist Member States and healthcare organisations meet the requirements set out in the Directive on Security of Network and Information Systems. Furthermore, the European Union Agency for Network and Information Security (ENISA) has acknowledged the significance of digital health networks as critical information infrastructures and has developed actions focusing on the security challenges and risks faced by the health sector in the Member States. Given that healthcare services have been recognised as a critical societal function, the Agency for Network and Information Security has analysed the degree to which various digital systems and infrastructures are critical for the secure provision of healthcare services and launched the eHealth Security experts group. In November 2016, the group provided an overview of recommendations to hospitals and healthcare organisations, comprising a combination of organisational and technical security measures to mitigate the risks resulting from cyber threats and corresponding vulnerabilities. Efforts to ensure coordination, monitoring and technical support provided to Member States in the implementation of technical and organisational security measures, are expected to continue as the Directive is transposed into national law.

2. Citizens' secure access to electronic health records and the possibility to share health data across borders 2.1. Electronic Health Record and digital access to personal health data Citizens requiring medical care when traveling or moving residence to another EU Member State are often confronted with the lack of access to their own medical records or medication. Access is particularly crucial when citizens seek emergency treatment while travelling outside their Member State of origin or residence or when they might be obliged to repeat procedures because they cannot access or re-use information from procedures completed recently in another healthcare institution. The current lack of electronic health record exchange formats that can be readable across borders limits the access of citizens and healthcare professionals to critical medical information about an individual receiving care in another country. This has an impact on the quality of care provided to European citizens. In some cases, the limited access to personal health data across borders, could adversely affect the safety of patients because of errors in medication lists and adverse drug reactions that otherwise could have been identified and avoided in time. The 2008 Commission Recommendation on cross-border interoperability of electronic health record systems and subsequent work carried out in the development of the European Interoperability Framework for eHealth (ReEIF) have so far not delivered cross-border access to electronic health records by healthcare professionals or ensured that citizens have the technical means to access and manage their personal health data. Beyond the lack of an established technical specification to support electronic health records that are readable across the EU, another major obstacle to implementation of interoperable cross-border access to electronic health records remains the extensive use of proprietary solutions and vendor lock-in models that increase both the cost and complexity of health information exchange efforts across the EU. Vendor lock-in undermines interoperability of electronic health record systems amongst healthcare providers in the EU and prevents the electronic health records from being readable across borders by healthcare institutions and professionals.

It is not only citizens that feel the adverse effects resulting from the current lack of interoperability of electronic health record systems across-borders. The absence of a common, shared open format at EU level to support interoperability of electronic health record systems increases barriers to open innovation, undermining business opportunities for innovative SMEs and negatively impacting the process and costs of digitising health information. Additionally, the existing lack of interoperability of electronic health record systems across the EU does not appear to bring benefits to EU economic actors in general. Despite the positive growth forecasts for the global market of electronic health record systems, EU companies maintain a persistently modest market share compared with their US counterparts, which have benefited from a domestic regulatory environment based on standardised and certified electronic health record systems. Furthermore, in the opinion of certain stakeholders, the current lack of interoperability of electronic health record systems across the EU significantly hinders the ability of the research community to access larger data-sets and make secondary use of health data, creating additional headwinds that limit progress in the fields of data-driven healthcare research, new health prevention strategies and personalised medicine. 2.2. State of Play 2.2.1. Lack of Electronic Health Records interoperability Currently, several Member States are progressing in implementing interoperable electronic health record systems within a national or regional level (figure 1). However, there is no co-ordinated solution or approach in place for a full-scale interoperability of electronic health records in a European context (figure 2). The landscape regarding the main levels of interoperability (legal, organisational, semantic and technical) remains fragmented and is widely considered to hinder effective cross-border flow of healthcare data, . The lack of interoperability among the electronic health record systems implemented within the Member States and the adoption of various, different standards constitute a major challenge leading to market fragmentation and to a lower quality level of cross-border healthcare provision. Market analysis of the European electronic health record market, performed by Frost & Sullivan in 2015, concluded that "the absence of a pan-European EHR strategy has worsened market fragmentation and continues to act as a barrier to electronic health record adoption". In this context, the absence of a pan-European electronic health record strategy was described as a major market restraint. Names of the standards World Health Organisation data indicates (see figure 2) that the current variety of national approaches regarding the use of standards for electronic health record implementation poses significant challenges to the development and implementation of effective electronic health record cross-border exchange. In the same study, funding, capacity, resources and infrastructure were also identified as very important barriers that hamper electronic health record implementation.

There are also major disparities between EU Member States in the deployment of electronic health records as part of an interoperable infrastructure that allows different healthcare providers to access and update health data in order to ensure the continuity of care of the patient. The same can be said about the approach taken to regulate electronic health records – some EU Member States have set specific rules for electronic health records, others rely on general health records and data protection legislation. While some EU Member States have set detailed requirements as to the content of electronic health records, others do not specify what this content should be. The level of details of the legislation on electronic health record content varies greatly from a simple reference to health data in general to exhaustive and detailed list of categories or data items. Regarding legal interoperability for cross-border electronic health record exchange in particular, few EU Member States have already established a relevant framework of legal provisions (figure 4). A reason behind the specific issue, according to the relevant study, is that the competent authorities perceive cross-border transfer of electronic health records as a challenge "that should be dealt with at the EU level and did not want to develop cross-border systems (e.g. through regional and bilateral agreements) that could potentially be in contradiction with the future action of the EU". 2.2.2. Citizens' access to electronic health records and cross-border exchange of health data amongst professionals European citizens have the right to access their health data. This right is enshrined in the General Data Protection Regulation, which gives also European citizens the right to share their health data with parties they designate for a given purpose (for instance, for medical treatment or research). In a recent Eurobarometer study, approximately 52 % of respondents confirmed they wish to have online access to their health records (including health data, prescriptions and medical records). However, only a limited number of citizens are currently enjoying this privilege. Only 9% of hospitals in Europe allow citizens to access online their own medical records, and most of those only give partial access. In 2008, Estonia became the first country in the world to implement a nationwide “birth-to-death” electronic health record system for nearly every citizen. However, since then only an additional 13 EU Member States have granted their citizens with some access to electronic health records, with the Member States deployment of electronic health records being greatly varied (see Figure 1). The use of ePrescriptions across Europe is equally diverse, with only a minority of Member States having it widely available to their citizens. The eHealth Action Plan, and more specifically the EU Cross Border Health Directive (2011/24/EU, Articles 11 and 14), include certain elements - namely electronic health records, electronic prescriptions (ePrescriptions) and telemedicine - that constitute crucial components to enable the emergence of innovative digital health and care solutions. The eGovernment Action Plan also aims to support Member States in the development of cross-border eHealth services. The digitisation and exchange of electronic health records and ePrescriptions can enable better provision of health and care of services to citizens, including when travelling across different Member States. Additionally, available studies show that the adoption of electronic health records and ePrescriptions across the EU could also generate efficiencies, and therefore contribute to the attainment of fiscal sustainability goals for health and long-term care systems. The percentage of hospitals exchanging electronically clinical care information about patients remains low: up to just 39% of hospitals exchange care information with other healthcare providers in the same country; whereas only 4% of hospitals do this with healthcare providers in another EU country. The percentage of general practitioners using electronic networks to exchange medical patient data with other healthcare providers and professionals varies greatly between Member States: from 91.8% of general practitioners in Denmark and 76.2% in the Netherlands to only 5.4% of general practitioners in Slovenia. Even in countries with high levels of domestic exchange of patient data, the exchange with healthcare providers in other EU Member States remains low. This is particularly relevant as the number of patients receiving treatment in another EU Member State continues to increase. Regarding patient and healthcare professionals' identification, as well as access rights to electronic health records, there is also a significant variety of available systems and approaches across the EU Member States. 13 Member States make use of a health insurance number for patient identification in their national eHealth systems, while 14 Member States use an ID card number approach, and two Member States are using other solutions. As for the identification and authentication of health professionals (e-Signature/ smart card), 15 Member States have an identification and authentication method and 16 Member States currently have access rights differentiated per type of health professionals. It is worth highlighting that eleven Member States have both elements in place in relation to health professionals. On the legislation part, several Member States have already adopted a legal framework for sharing digital data through electronic health records between health professionals at the national level. However there is limited evidence to suggest that the adoption of a legal framework has contributed to cross-border sharing of electronic health records data as depicted in the next figure:

Cross-border exchange of health data is starting to take place, based on voluntary co-operation between the Member States. Under the telecommunications sector of the Connecting Europe Facility eHealth call on Digital Service Infrastructure for cross-border exchange of Patient data and ePrescription instigated active co-operation of Member States in these areas. Sixteen Member States obtained EUR 10.6 million of EU funding to be part of a secure peer-to-peer network allowing the exchange of Patient Summaries and/or ePrescriptions, as a first step towards seamless cross-border care and secure access to patient health information between European healthcare systems. The eHealth Digital Service Infrastructure aims to enable medical personnel to obtain life-saving information in unplanned care situations and reduce the repetition of diagnostic procedures. When a citizen makes an unplanned visit to a healthcare provider abroad, within the European Union, the eHealth Digital Infrastructure will allow the healthcare professional to have access to their Patient Summary. Furthermore, the ePrescription services will enable the patient to receive abroad the equivalent medication treatment that they would have received in their home country. A second call in 2017 allowed 6 more Member States to join this cross-border exchange of health data. In 2018, for the first time several Member States will start exchanging Patient Summaries and ePrescriptions across borders. The solutions used in the eHealth Digital Service Infrastructure build upon the achievements of pilot projects that successfully tested the exchange of personal health data between Member States and developed related open specifications and software, in particular the epSOS project and the EXPAND project; as well as the guidelines on Patient Summaries and ePrescriptions developed by the eHealth Network. The European Interoperability Framework was a point of reference for these projects. 2.3. Remaining challenges at the EU-level Cross-border access to and portability of personal health data: Despite over a decade of Commission recommendations and voluntary cooperation in the definition of electronic health record standards, the market has so far not delivered electronic health record solutions that are interoperable across borders, mainly due to the prevalence of electronic health record systems based on closed proprietary solutions. It clearly undermines the full realisation of a digital single market for digital health and care solutions and disadvantages European companies, notably SMEs that are unable to compete with the established commercial vendors of closed proprietary electronic health record systems. Even with the eHealth Digital Service Infrastructure in place, the potential expansion of cross-border exchange of health data beyond ePrescriptions and Patient Summaries to full electronic health records encounters challenges: ·Firstly, there are barriers to overcome at national level, such as the need to ensure interoperable connectivity among systems within the national level (e.g. among hospitals, general practitioners, primary care centres and pharmacies within each Member State). ·Furthermore, the cross-border exchange of health data sets wider than Patient Summaries and ePrescriptions asks for further interoperability issues to be resolved. This would in turn require taking intermediate steps (such as aiming for cross-border exchange of e.g. discharge letters and data related to chronic conditions) on the way to full electronic health record exchange, while, in parallel, configuring an exchange format for full electronic health records. ·Finally, mechanisms to sustain the voluntary co-operation between Member States would be required, which in turn calls for configuring sustainable governance and financing arrangements. The question of the long-term sustainability of the Digital Service Infrastructures beyond the Connection Europe Facility programme was assessed in the study "Long-Term Sustainability of Digital Service Infrastructures". The VALUeHEALTH project proposes an evidence-based business plan for sustainable interoperability, with sustainable revenue streams for developing and operating priority pan-European eHealth Services beyond 2020. Ultimately though, the number of citizens who will have electronic access to and benefit from portability of their personal health data will depend on the level of deployment of interoperable eHealth solutions in national and regional health systems in Member States. Besides the well-recognised need to overcome interoperability issues, achieving wide deployment of electronic health records and ePrescriptions at national scale requires significant investments. More targeted use of EU funds by health authorities – such as the European Structural and Investment Funds and the European Fund for Strategic Investments - can be instrumental in mobilising further investments from the public sector and private investors alike. The use of open standards and interfaces, such as OpenEHR currently in use in some Member States, fosters semantic scalability, provides a vendor-neutral approach and supports flexible interoperability among the various electronic health record solutions implemented in the Member States. The building of open ICT systems based on the exploitation of standards has already been identified as a good practice that will increase competition, promote efficiency and support the development of innovative services that can be used by citizens or public authorities. Some Member States have started to address the unsustainable costs of maintaining proprietary closed systems that cannot integrate with other data ecosystems. The creation of an agreed exchange format (technical specification) at EU level - to ensure that data from electronic health records can be accessed cross-border and patients can provide access to their data concerning health to a doctor in another EU Member State (for example when consulting a specialist, receiving emergency treatment or providing access for secondary use in research) - could be achieved through EU-level cooperation in the development of technical specifications. Cross-border interoperability of electronic health record systems can allow citizens to receive care when travelling or living in another EU Member State, by providing access to their health data. According to stakeholders, interoperability of electronic health record systems will also positively impact EU SMEs and innovative companies competing in the global digital health market, and provide new opportunities for the EU research community to access large scale data sets from electronic health records, often required for the development of new personalised treatments and medicines. However, there are no inherent incentives for proprietary electronic health record systems developed and implemented at national or regional level to become interoperable. Experiences from other world regions suggest that strong regulatory incentives are necessary in order to create market demand for cross-border interoperability solutions and to avoid the need to retrofit electronic health record interoperability only at the EU level in order to remedy existing market fragmentation and piecemeal adoption of relevant solutions. With the introduction and widespread adoption of a European Electronic Health Record (EEHR) exchange format, based on open technical specifications, citizens could be empowered to use their personal data concerning health across borders, share it with authorised healthcare professionals and make informed decisions about their health. The EEHR exchange format will support the shift to a patient-centred or patient-driven healthcare provision model where the patient is empowered by data. Access to their personal data by patients could overcome the difficulties and obstacles deriving from the lack of cross-border electronic health record interoperability and according to Auffray et al. (2016) "provide a wide range of new health service business opportunities with major economic potential and unleash new ways to stimulate a competitive health-driven economy". Health and care practitioners would have quick access to a more comprehensive view of the patient’s medical background and history, regardless of their location in the EU, enabling them to reach a reliable and accurate diagnosis quicker than before, to reduce medical errors and to provide safer treatment outside the patient's country of residence, while simultaneously ensuring the protection of personal data and conﬁdentiality.



3. Better data to advance research, disease prevention and personalised medicine

3.1. Fragmented data and computing capacity At EU level, there has been a wide recognition that the use of health data to advance research and develop personalised medicine has the potential to offer significant benefits for patients and healthcare systems. Over the past years, personalised medicine has gradually gained recognition as a useful tool for healthcare organisations across different disease areas. Physicians are increasingly welcoming therapies supported by data analytics which have the potential to replace trial-and-error with precision diagnosis and treatment, benefiting both the provider and recipient of health and care services. An estimated 70 % of citizens in the Union would be ready to share their personal health and wellbeing data (medical and care data, lifestyle, physical activity, nutrition, etc.) to support scientific research or improve treatment and early diagnosis of disease. However, for the time being there is no secure, commonly accepted infrastructure at EU level to enable federated access to health data that can support personalised medicine across the EU. The absence of an agreed set of ontologies creates a high level of uncertainty around the quality of capturing and processing of health data. Lack of interoperability between data sources and limitations in data storage and computing capacity, as well as the different legal regimes set forth at national level to further specify the GDPR for the access and processing of health and health-related data across the EU, remain the major obstacles to effectively pooling data and resources at EU level and translating health data into better health and care outcomes. Over the past decade the volume of data generated from medical research and healthcare has grown exceptionally fast. The annual data generation is estimated to a 4300% annual growth between the period 2012 and 2020. Big data in health encompasses high-volumes, high-diversity biological, clinical, environmental, and lifestyle information collected from single individuals to large cohorts, in relation to their health and wellness status, at one or several time points. The amount of data produced by sequencing, mapping, and analysing genomes is considerable. Each human genome has 6 billion ‘letters’ and when sequenced generates approximately 100 gigabytes of data. Therefore, analysing and storing genomes at scale rapidly runs into petabytes or even exabytes of data storage and performance requirements. When combining this with other applications (such as transcriptomics and metabolomics), technologies (such as imaging and patient monitoring) and with clinical, personal and environmental data, the requirements become considerable and require both advanced computing performance and significant storage capacity. A major challenge faced by healthcare authorities, practitioners and scientists is being able to bring this wealth of data together and interpret a genomic finding in the context of the individual patient. There is a need to share data, deriving the knowledge gained from data at a population level to sort through the ‘noise’ of variation in a person’s genome to identify the ‘signal’, an individual change or pattern that may be unique to an individual. The quality of conclusions on the aetiology of diseases follows a law of large numbers. Cross-sectional cohort studies of 30,000 to 50,000 or more cases are required to separate the signal from noise and to detect genomic regions associated with a given trait in which disease-related genes or susceptibility factors are located . Even some of the largest national programmes to aggregate -omics data, such as the UK Government-funded 100,000 genomes project, or France’s Médecine Génomique 2025 which will establish capabilities for sequencing over 200,000 genomes a year, will have a limited number of individuals that share the same genetic mutation and indeed often relatively few patients with a specific condition, particularly for rare disorders. Another challenge lies in the pooling of different data-sets from a wide range of sources, including human (e.g. community, hospital or laboratory health services) and animal health surveillance, health registries, microbial and viral genomic data, pathogen resistance data, mapping of vectors, climate and environmental data, as well societal data that are correlates of disease. Linking these datasets for extended data mining purposes can open up possibilities for improved early warning and detection of infectious disease health threats, bolster the tracking and control of infectious diseases outbreaks, and enable rapid and personalised treatment of infected patients. 3.2. State of Play 3.2.1. Digital infrastructure to support research and personalised medicine The scientific and research community is increasingly engaged in a debate about the merits and advantages of creating a sustainable and effective ecosystem that brings together cross-border access to data-sets, computing capacity to analyse and process that data, knowledge and scientific expertise needed to accelerate the translation of big data into real outcomes for citizens and healthcare systems across the EU. The EU has invested over EUR 2.6 billion in personalised medicine research and innovation in Horizon 2020 and its predecessor Framework Programme 7. High-performance computing involves thousands of processors working in parallel to analyse billions of pieces of data in real time. High-performance computing allows to design and test new medicines, simulate their effects, and provide faster diagnosis, better treatments and personalised healthcare. Currently, EU industry provides approximately 5% of high-performance computing resources worldwide, but consumes one third of them. In April 2016 in the European Cloud Initiative – part of the EU's strategy to digitise European industry – the Commission urged Member States to step up cooperation in high-performance computing to boost Europe's scientific capabilities and industrial competitiveness. It also committed to develop a high-performance computing ecosystem based on European technology, including low power chips. Several Member States agreed in March 2017 to work together with the European Commission to support the next generation of computing and data infrastructures, within the framework of a European project. The plan is to establish the European High-Performance Computing Joint Undertaking for acquiring and deploying an integrated world-class high-performance computing infrastructure capable of at least 1018 calculations per second (so-called exascale computers). This will be available across the EU for scientific communities, industry and the public sector, no matter where the users are located.

The European High-Performance Computing Joint Undertaking initiative builds on existing cooperation initiatives among Member States, industry and science stakeholders such as the Partnership for advanced computing in Europe (PRACE), the European technology platform for High Performance Computing (ETP4HPC) and the pan-European data network for the research and education community linking national research and education networks across Europe (GÉANT). The European Commission proposed the new legal instrument European High-Performance Computing Joint Undertaking with a view to have the HPC initiative operational by 2019. Advanced high-performance infrastructure and services will then be available to industry and SMEs, as well as the public sector among others. This will also support the European Open Science Cloud and allow millions in the research community to share and analyse data in a trusted environment across technologies, disciplines and borders. The European Open Science Cloud aims to give Europe a global lead in scientific data infrastructures, to ensure that European scientists reap the full benefits of data-driven science. Practically, it is expected to offer 1.7 million European researchers and 70 million professionals in science and technology a virtual environment with free at the point of use, open and seamless services for storage, management, analysis and re-use of research data, across borders and scientific disciplines. The results of the consultation with stakeholders and Member States show that its development should be driven by the scientific community, who are the most advanced users and the largest producers of science in the world. It also shows that the European Open Science Cloud should be also open for education and training purposes in higher education and, over time, to government and business users as the technologies developed will be promoted for wider application. As announced in the Commission’s Communication of 19 April 2016, Horizon 2020 would be used to integrate and consolidate e-infrastructure platforms, to federate existing research infrastructures and scientific clouds and to support the development of cloud-based services for Open Science. This will make access to scientific data easier, cheaper and more efficient. It will enable the creation of new market opportunities and new solutions in key areas such as health, environment, or transport. The European Open Science Cloud will provide a secure environment where privacy and data protection must be guaranteed by design, based on recognised standards, and where users can be confident concerning data security and liability risks. It is envisaged that the establishment of the European High-Performance Computing Joint Undertaking Joint Undertaking and the European Open Science Cloud will provide a solid basis for the enhancement and further development of personalised medicine in Europe. This will however rely on access to health data-sets and integration with European scientific and knowledge networks in the respective fields of application. 3.2.1.1 The opportunities from data clouds and exascale computing for personalised medicine Genome sequencing and analysis are complex tasks that demand powerful analytics platforms. The time needed for sequencing has been reduced considerably in recent years, making it possible to drastically increase the amount of genomic data collected on large study populations. This opens the way to new omics- based improvement of healthcare services, leveraging in depth and comprehensive genomic analyses for a predictive and personalised medicine that can achieve better and predictive diagnosis, more efficient treatments and customised therapies. To achieve this, sequence analysis must be available on a large-scale, and complex analytics must be supported by adequate computing technology. This requires computational power and data storage capabilities on an unprecedented scale. Cooperation within the Union can help achieve this scale. For example, by joining medical research, data-sets and high-performance computing, there are major new opportunities for personalised and optimised treatment options for cancer based on analysis of genetics and other data sources. In a typical cancer study today, more than eight million measurements are taken from the biopsy of a single tumour. But as current technologies allow researchers to characterise the biological components of cancer with greater levels of accuracy, the substantial amounts of data generated by these technologies have out-paced the ability to quickly and accurately analyse them. To tackle these complicated and consequential personalised medicine problems, researchers globally are looking towards the promise of exascale computing combined with advanced data analytics, modelling and simulation on the basis of very large data-sets. This has the promise to detect risks much earlier and to develop precise options for personalised interventions. 3.2.2. National and international initiatives on personalised medicine Omics data are central to advance personalised medicine and progress in genomic sequencing has produced a fundamental change in clinical and translational research over the past decade, leading to improved success in discovery and development of new treatments and diagnosis of disease. Development of major initiatives in genomics and personalised medicine is a global trend with significant investments being committed, for example by the governments of the United States (1 million genomes and EUR 3.8 billion planned investment) and China (100 million genomes and EUR 7.9 billion planned investment). In Europe the most comprehensive initiatives, encompassing clinical implementation, research and enterprise, are being seen in Member States such as the UK (100,000 Genomes Project) and France (Médecine Génomique 2025). There has also been significant long-term investments and strategies relating to genomics, with skills and infrastructure developed in countries such as Estonia, Denmark, Iceland, and Finland; and others leading in the clinical application of genomics, such as the Netherlands. Major genomics programmes provide a basis for a more personalised medicine leading to more efficient healthcare systems and stimulating economic returns. Project Origin and funding Purpose 100,000 GENOMES PROJECT (UK) UK UK government; funding in excess of £300 million to date Sequencing and analysis of 100,000 genomes to inform the diagnosis of patients with cancer and rare diseases. Its four main aims are to: 1.Create an ethical and transparent programme based on consent; 2.Bring benefit to patients and set up a genomic medicine service for the NHS; 3.Enable new scientific discovery and medical insights; 4.Kick-start the development of a UK genomics industry. DANISH GOVERNMENT AND REGIONS NATIONAL STRATEGY FOR PERSONALISED MEDICINE 2017-2020 DK Danish Ministry of Health and Regions; initial funding of DKK100 million Strategic action areas: 1.Transparent governance structure with nationwide involvement 2.Clear legal framework addressing ethical principles and data privacy and security 3.Patients and citizens must be involved 4.A technological infrastructure with secure, efficient and equal access 5.Genomics research must be international and deeply integrated in the healthcare system 6.Tools and competencies to use genetic data 7.Attractive development in relation to personalised medicine ESTONIAN GENOME PROJECT EE Estonian Government The project was proposed as being of huge cultural value and leading in this area in global research. It is has collected over 50,000 samples (5% of adult population) and links this to clinical and survey data to form a rich data set. Genotyping analysis has been performed on these samples, along with sequencing in a proportion, along with additional samples and investigations in many. There are ambitions to grow it further to cover a significant percentage of the population and embed genomics within the health system as part of clinical decision support. It has gathered significant awareness and support across a large proportion of the population. FINLAND’S GENOME STRATEGY FI Ministry of Social Affairs and Health, Finland; funding of The aim of the strategy is to 1.Make Finnish healthcare more effective through better and more targeted care, with integration of genomics in clinical care, individuals able to make use of their genomic data, and a containment of healthcare costs and better allocation of resources; 2.Researchers will have entirely new opportunities for utilizing genomic data; 3.Transform Finland into an internationally attractive environment for research and business in the field of genomics FRANCE MÉDECINE GÉNOMIQUE 2025 FR French Government; investment of €670 million in public-private partnerships Targets of the 2025 France Genomic Medicine Plan 1.Position France among the leading big countries in the field of genomic medicine within the next ten years, with the aim of exporting expertise and developing a strong medical and industrial framework; 2.To establish a generic care pathway with access to genomic medicine for all French people affected by cancer, a rare disease or a common disease; 3.To be capable by 2020 of sequencing 235,000 genomes a year for rare diseases and cancer, with growth beyond 2020 to cover common diseases. NHS ENGLAND PERSONALISED MEDICINE STRATEGY UK NHS England lead the National Health Service in England Aims aligned to Five Year Forward View and health sustainability: 1.Improved prevention based on underlying predisposition; 2.Earlier diagnosis of disease as a result of identifying abnormality earlier; 3.More precise diagnosis based on cause; and 4.Targeted interventions through the use of companion diagnostics to identify and stratify effective treatments. PERSONALISED MEDICINE – ACTION PLAN (GERMANY) DE Federal Ministry of Education and Research, Germany (BMBF); up to €360 million funding Strategic funding for research in personalised medicine. Targeted across R&D from biomarker validation through to therapies and service implementation. Main goal is for patients to benefit more quickly. Ethical, legal and economic challenges and engagement and information platforms are also included within this. PRECISION MEDICNE INITIATIVE (CHINA) CN Chinese Government; expected funding of ¥60 billion (€7.9 billion) by 2030 The Chinese government confirmed plans to make precision medicine part of its Five Year Plan for 2016-2020 as it works to prioritise genomics to drive better healthcare outcomes. PRECISION MEDICNE INITITATIVE ( ALL OF US - USA) US US Government; initial funding of over $200m Aim is to enrol one million or more volunteers to enable research for a wide range of diseases and increase our understanding of healthy states. Scientific opportunities presented by All of Us include: the ability to: 1.Develop ways to measure disease risk based on environmental and genetic factors; 2.Pharmacogenomics; 3.Biomarker identification and validation; 4.Use mHealth technologies to correlate activity, physiological measures and environmental exposures with health outcomes; 5.Develop new disease classifications and relationships; 6.Empower study participants with information to improve their health; 7.Create a platform to enable trials of targeted therapies. The Commission has contributed to several large scale international initiatives aiming at collecting harmonised and standardised omics data for research purposes. This includes the International Human Epigenome Consortium (IHEC) which coordinates the production of reference maps of human epigenomes for key cellular states relevant for health and disease. Common bioinformatics standards, data models and analytical tools are used to organise, integrate and display whole epigenomic data for use by the research community. The EU contributed EUR 30 million to the BLUEPRINT project which delivered more than 100 reference epigenomes relevant for diseases of the haematopoietic system to the IHEC Data Portal. The EU has also contributed to the mapping of cancers through the International Cancer Genome Consortium (ICGC). The ICGC Data portal include comprehensive description of genomic, transcriptomic and epigenomic changes in 50 different tumour types and/or subtypes which are of clinical and societal importance across the globe. These and other initiatives are also interacting with the Global Alliance for Genomics and health (GA4GH) which aims to contribute to the policy-framing and technical standards-setting to enable responsible genomic data sharing. Further efforts in the area of mapping the microbiome, and to establish an atlas of all human cells are important next steps towards the better understanding of human health and disease. Under the leadership of the European Commission several initiatives related to personalised medicine have come together and in November 2016 the International Consortium for Personalised Medicine (IC PerMed) was launched. IC PerMed is a Member States led initiative which brings together research funders and policy-making organisations from 28 countries to coordinate research and health policy to advance the implementation of personalised medicine. A first action plan has been released in March 2017, in which 8 of 22 research actions concern research on standardising and sharing of data.

3.2.3. Initial areas of application Several areas of application already gather the scientific expertise and the basic semantic frameworks to support data exchange and data-sets that can allow for significance in findings and development of new solutions. 3.2.3.1. Diagnosis and personalised treatment of rare diseases Around 30 million EU citizens are affected by an estimated 5000 to 8000 life-threatening or chronically debilitating rare and complex diseases. Patients with rare diseases often spend years waiting for the correct diagnosis and most rare diseases lack efficient therapy and cure. With small and dispersed patient populations in each country, advanced clinical and scientific expertise on rare diseases is fragmented, scarce and scattered in different laboratories and knowledge centres throughout the EU. This scarcity of expertise translates into poor access to specialised care for those suffering from rare diseases, delayed diagnosis, and fewer products and therapies as research and development investment in medicinal products for rare disease treatments is low. The EU invested over EUR 1 billion for rare diseases research in Horizon 2020 and its predecessor Framework Programme 7. Set up under the Directive on Patient Rights in Cross-Border Healthcare, the 24 European Reference Networks on rare, low prevalence complex diseases are virtual networks from 25 European countries including Norway bringing together more than 900 healthcare units in over 300 hospitals across Europe to tackle rare or complex diseases and conditions that require highly specialised healthcare and a concentration of knowledge and resources. Connected through a dedicated IT platform financed by the telecommunications sector of the Connecting Europe Facility, the European Reference Network can convene a "virtual" advisory board of medical specialists across different disciplines to review the patient's case for diagnosis and treatment. The European Reference Networks will give healthcare providers access to a much larger pool of expertise and knowledge, increasing the chances of patients suffering from such conditions and diseases to receive the best advice to treat and diagnose their condition. The European Reference Networks will serve as research and knowledge centres stimulating new innovative treatments and therapies for patients across the EU and the development of eHealth tools to enhance access to care. The development of a data infrastructure would enhance the potential use of the European Reference Network patient data, with patient consent, for research, new therapies and better care outcomes. Pooling data and computing capacity from different countries is the only way to achieve a sufficient sample size for epidemiological and/or clinical research, to improve the understanding of the natural history of rare diseases and of the patient phenotypes, necessary to make progress in the diagnosis and treatment of rare diseases. Cooperation within the Union and between Member States and EU funded actions in the field of rare diseases allow to pool resources, knowledge and expertise. RD-Connect has developed an integrated platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research in which complete clinical profiles are combined with –omics data. The platform accepts data from other projects funded nationally, at EU or international level. RD-Connect collaborates closely with two other EU-funded projects EuRenomics and Neuromics focussing on the molecular characterisation of a large group of rare diseases using “-omics” technologies. Their work has helped understand disease mechanisms and opened avenues for new diagnostic tools and therapies. Standardised formats are used for the description of the diseases and their detailed phenotypic characteristics based on the Orphanet Rare Disease Ontology (ORDO) and the Human Phenotype Ontology (HPO) promoted by the International Rare Diseases Research Consortium (IRDiRC). The current work programme of Horizon 2020 includes a topic for Rare Disease European Joint Programme Cofund which aims to create a research and innovation pipeline "from bench to bedside" ensuring rapid translation of research results into clinical applications and uptake in healthcare for the benefit of patients. EU contribution of EUR 50-55 million is reserved for the topic. There is no established digital infrastructure to support cross border access to relevant health data for research. For example, while the recently established European Reference Networks (ERNs) on rare, low prevalence complex diseases are breaking new ground in cross-border healthcare, the lack of a European digital infrastructure leads to a high level of fragmentation in terms of rare disease data-bases and patient registries, and the same applies to other fields. Common data structures, coding systems, terminologies and standards are crucial for the semantic interoperability and comparability of rare disease data. The Orphanet nomenclature improves the interoperability of rare disease systems and, by harmonising rare disease codification, adds value to the re-usability of data for research. The EU funded Orphanet, the largest global repository of rare disease information and therapies, is key to maintaining the interoperability tools Orphacode and ORDO ontology. Its further development is fundamental for rare disease diagnosis, treatment and research. To overcome the fragmentation of rare disease patient data contained in over 600 patient registries across Europe, the European Platform for Rare Diseases registration (EU RD Platform) provides EU standards and recommendations for rare disease data collection and sharing. In October 2017, the EU RD Platform defined a "Set of Common Data Elements for Rare Diseases Registration". Improving the interoperability of patient registries enables the critical mass of data necessary for epidemiological, clinical, translational, pharmacological and other studies and research at European level, thus supporting knowledge generation on rare diseases and helping to improve diagnosis, treatment and care for rare disease patients. 3.2.3.2. Anticipation, rapid EU-wide identification and quick response to epidemics Next generation genome sequencing and analysis, as well as mining of pooled Big Data, can improve the anticipation of epidemics and accelerate EU-wide identification of infectious threats (within days), thus allowing swift response to infectious outbreaks. These tools are made possible by novel IT infrastructure (high-performance computing, high-speed internet transfer) and advanced IT technologies which are needed to rapidly process, transfer, store and compare the relevant data and meta-data. Worldwide, infectious diseases are responsible for around 20% of all deaths. Increasing global travel and trade enhance the potential for infectious diseases to spread. At the same time, the evolution of viruses and bacteria means that there is a constant risk that new diseases may emerge as well as different more virulent forms of existing diseases may emerge. When they are not contained these diseases can have devastating human, social and economic impact, as was demonstrated by the 2014-2015 Ebola epidemic and the 2009 influenza pandemic. Countering these threats requires: - comprehensive modelling to more accurately predict the possibility and trajectory of potential future outbreaks. These risk prediction models are based on the integration and comparative analysis of diverse Big Data sets e.g. climate and geo-observation data, demographic and population movement data, human and animal health data, disease vector surveillance etc.; - well-functioning surveillance systems able to rapidly identify infecting organisms (based on next generation sequencing and analysis); - integration of surveillance data with real-time information e.g. vaccination coverage, data from health registries, hospitals and laboratories, and societal data from informal/non-traditional sources like social media or health apps in order to map the evolution and guide management of the epidemic. Science to support better preparedness and response capacities for infectious disease threats is a rapidly developing field increasingly based on digital tools. So far under Horizon 2020, at least EUR 456 million has been committed to relevant preparedness research for infectious diseases. The Horizon 2020 project COMPARE, addresses the challenges and the opportunities linked to these advances, as a large-scale pilot. With a budget of almost EUR 21 million, COMPARE brings together key national reference laboratories from 10 EU countries. The project is developing a globally linked data and information sharing platform that uses advanced IT technologies to generate genomic data of infectious pathogens and integrate these data with other relevant (clinical, epidemiological, demographic, environmental etc.) data. It aims to facilitate rapid identification of emerging infectious threats in human health, animal health and food safety. Similar application of high-performance computing on genomics were also used during the Ebola outbreak, by the EU-funded project EVIDENT, which researched the mutational rate of the Ebola virus during the West African epidemic and performed real-time molecular epidemiology based on sequencing in the field.

Projects like COMPARE and EVIDENT provide insight on how supercomputing capacity and artificial intelligence, bringing together large data sets from different sources and disciplines, can improve the understanding of epidemics, and accelerate EU-wide identification of infectious threats. Advanced IT technologies can also support the development of new risk models to predict the possibility and trajectory of potential future outbreaks, by facilitating the integration and comparative analysis of inputs from various data sources, e.g. from human and animal health data, vaccination coverage, vector surveillance, laboratory data, environmental data, population density, travel, etc. EU research funds have already supported the development of such models for vector-borne diseases in general (cf. EDENext project) as well as disease-specific models e.g. for Dengue (cf. DENGUETOOLS project) and Zika (cf. the ongoing ZikaPLAN and ZIKAlliance projects). From a very different perspective, the TELL ME project used social simulation models to understand the complex relationships between communication, personal protective behaviour and the spread of an (influenza) outbreak. The abovementioned projects illustrate the potential of advanced IT technologies for improved preparedness, early detection and response of infectious disease threats. The challenge now is to make sure that these piloted applications are expanded towards a common and large-scale use across the EU. Allowing for a swift response to infectious outbreaks, such technologies can support the reduction of outbreak-associated human, health system, and socioeconomic impact, and contribute to an increased protection of European citizens. 3.2.3.3. Real World Data (RWD) in healthcare Big data in health may come from a variety of sources including social media, physical activity trackers, electronic health records, insurance claim databases, patient registries, health surveys and observational studies, provided that the requirements of the GDPR are complied with. Real world data is big data, but the term specifically refers to any type of data not collected in a randomised clinical trial. This data can complement randomised clinical trial data to fill the knowledge gap between clinical trials and clinical practice, provide new insights into disease patterns and help improve the safety and effectiveness of health interventions. Patients selected for randomised clinical trials often have characteristics, experiences, and treatment protocols that differ from patients in daily practice and therefore it may not be possible to generalise the information gained in randomised clinical trials to a broader group of patients. There can also be a large uncertainty on the health gain obtained with a new product based on randomised clinical trial findings due to possible differences in the way patients and healthcare providers are going to use the product in real life. Randomised clinical trials may also be particularly difficult to conduct for some health interventions when the size of the population to be treated is small. This applies in the case of orphan products and may apply to personalised medicines. Moreover, due to the typically short follow-up of randomised clinical trials, long-term health outcome cannot always be captured. Cost-effectiveness analyses are thus often based on predicted outcomes relying on intermediate or surrogate outcomes. Real world data is increasingly used for regulatory purposes and Health Technology Assessment. The objective is to provide (early) access to innovative health interventions while ensuring safety and efficacy. After authorisation, real world data can contribute in the health technology assessment process by better predicting the effectiveness of the new treatment in daily practice or to serve as input in payment model such as outcome-based managed entry agreement. In such cases, price and reimbursement conditions that have been agreed on at launch can be reviewed over time, comparing real world data with initial predicted health outcomes. Challenges related to the use of real world data However, despite technological advances in big data mining and analytics, there are a number of issues that prevent the wider use of real world data. In particular, generating, collecting, storing and exploiting such real world data poses methodological and legal challenges regarding the further processing of data as there is no widely accepted regulatory guidance. In this context, Regulatory Science can enhance the scientific basis of the regulatory process, by integrating data from relevant sources outlined above. These include Electronic Health Record information, Real Word Data and other healthcare parameters. It offers an incentive to accelerate understanding of the spectrum of action of potentially new healthcare products in ways pertinent to the personalisation of healthcare. EU actions to support use of Real World Data Increasing the use of real world data is being addressed through a variety of EU initiatives in the fields of research, regulation of medical products, therapies and health technology assessment. The Joint European Medicines Agency and Head of Medicines Agencies (EMA/HMA) Task Force on Big Data is exploring how medicine regulators can use real world data to support research, innovation and medicines development for the benefit of human and animal health. The Joint Action European Network for Health Technology Assessment is producing evidence generation, with a focus on patient registries and, looking to the future, the European Commission plans to strengthen EU cooperation on health technology assessment post 2020, including issues related to real world data generation and use. In the area of transplant medicine, the Commission, national competent authorities and professionals are exploring how real world data could be integrated into regulatory oversight. Additionally, the public-private partnership Innovative Medicines Initiative is making an important contribution to realize the potential of Big Data, including real world data in the context of European healthcare. However, more efforts are needed to guide clinicians, researchers, regulatory and health decision-makers on the collection and translation of real world data into meaningful health outcomes. The outcomes and lessons learned from some of the initiatives could catalyse such efforts and be highly instrumental for the development of EU level guidance to engage data holders to optimize real world data collection, sharing and use. For example: ·The European Medical Information Framework project (EMIF-AD & EMIF-Metabolic) aims to federate heterogeneous sources of real world data to help researchers understand how treatments work when applied in clinical practice environments and provide new insights into disease patterns. Methodology and tools developed in these projects can be used to improve both medical product safety and effectiveness by targeting subgroups of patients who stand to benefit the most. ·In the area of product development (in view of regulatory process), the Electronic Health Record for Clinical Research (EHR4CR) aims to facilitate clinical trial design and patient recruitment which in turn allows to shorten clinical trial phase and accelerate access for patients to new treatments, targeting patient population, lowering clinical trial costs. ·To support the Health Technology Assessment (HTA) process, the GET REAL project aims to provide methods and tools to better assess the effectiveness of the new treatment in daily practice (e.g. methods to combine randomised clinical trial data and real world data). In addition, two H2020 projects (IMPACT-HTA and COMED) that started in January 2018, investigate the same issue. ·To support the regulatory process, the development, authorisation and vigilance of (novel) transplant and transfusion therapies, the GAPP Joint Action (facilitating the authorisation and preparation process for blood, tissues and cells) is engaging 27 regulatory authorities and professional associations to provide a stronger evidence basis through the use of clinical real world data by regulatory authorities. In addition to these initiatives on real world data, several EU-funded projects working on big-data (including MIDAS, BigO, IASIS, PULSE, CrowdHEALTH, EVOTION) focus on how to better acquire, manage, share, model, process and exploit data to develop integrated solutions that support public health authorities in healthcare system management, long-term policy making and increase the ability to provide actionable insights at the point of care. Bigmedylitics, a large scale pilot of EUR 17 million (EUR 15 million of EU funding) was launched in January 2017 to deliver a big data healthcare analytics platform and components, enabling data integration to support healthcare innovation. It involves 12 large scale pilots in different fields of application.

3.3. Remaining challenges at the EU-level It is widely acknowledged that not one Member State alone will be able to develop the expertise, data capacity and infrastructure needed to accelerate diagnosis, personalised treatment and prevention of diseases, particularly if compared with major emerging initiatives on personalised medicine such as those being pursued in the United States and China. EU actions to support coordinating national and regional initiatives in personalised medicine and genomics, and the establishment of a digital infrastructure with associated technical agreements to allow sharing of expertise and distributed access to health data sets stored in different locations across the EU, could help the EU Member States remain competitive in providing the Union's population with the most advanced medical and care solutions. This could also allow them to explore the potential of innovation to support the future sustainability and resilience of healthcare systems. If the Union can achieve the scale to match other investments in the global race for personalised medicine, European companies may be better positioned to capture investment and explore personalised medicine solutions, allowing EU citizens access to innovative and personalised therapies. It is equally important to explore synergies between the EU and Member States research and innovation actions, particularly defining together the areas of future pilots that can exploit the potential of genomic data at the EU-level. Cooperation with health professionals will also be a key element for the success of data driven innovations in healthcare and for taking advantage of the new opportunities arising from big data, such as interpretation of information for genetic assessment to improve diagnosis and treatment. Faster scientific advances can be achieved through pooling resources at EU-level. Pooling resources in a decentralised / distributed model that provides cross-border access to expertise, data and computing capacity (without centralising these resources) can accelerate research in areas such as genetics, cancer treatment or infectious diseases outbreaks and is only possible through EU cooperation encompassing a network of multiple public authorities and research organisations across the EU. Maximising the use of real world data can fill knowledge gaps between clinical trials and clinical practice; however more efforts are necessary to engage and guide stakeholders, in particular clinicians, into the sharing of such data. Faster diagnosis and more personalised treatment of rare genetic diseases can be achieved if scientific expertise and data are pooled across borders, significantly reducing the estimated 5.6 years on average that it takes to diagnose a rare disease in Europe. With high performance computing, infectious diseases can be identified earlier, preventing outbreaks across the EU. Access to larger volumes of health data pooled securely across borders maximising the potential of Exascale high performance computing could vastly improve and accelerate development of new therapies. Freedom of movement requires EU-wide coordination is necessary for an effective and sustainable response to infectious threats across the Union territory. The EU is ideally placed to support the protection of EU citizens and Member States from major public health threats, by helping to prevent health threats spreading and providing rapid responses when a threat emerges - but also helping to ensure that there is a robust data and computing capacity to anticipate epidemics. Personalised treatments for complex diseases like cancer require the ability to process very large amounts of data, while applying methods of interpreting data and extracting new knowledge such as computer modelling, machine learning or artificial intelligence. Personalisation of health requires interconnection of data sources (patient, hospital, bio-banks), biological levels (molecular, genetic, imaging, behavioural), and disciplines (medicine, pharmacology, social sciences and humanities). A convergent effort to build a whole new framework focused more on big data is needed, able to understand the molecular interactions and to support diagnostic image processing and running of predictive models, in order to diagnose much earlier and to select the best therapeutic strategies. This framework needs to be based on advanced computing and clever algorithms. While clinical applications may need a combination of multiple computational strategies adapted to the heterogeneity of data and careful protection of sensitive data, simulations in research (that can complement the testing of biomedical products and other experimental results) process and also generate new data likely to require exascale computing. Covering gaps for both health and research data infrastructures will significantly improve the understanding of cancer and, consequently, the impact of cancer treatments. European and Member States research is supported today by multiple initiatives that continuously generate data. A few platforms/repositories for medical data and computer-models storing/sharing and for clinical workflows simulations exist. Based on the use of high-performance computing and cloud infrastructures, they show how dedicated health data infrastructures can advance research and personalised medicine in medical applications like brain aneurysm, leukaemia and solid cancers. The mapping and connecting of these initiatives using cloud and high-performance computing data infrastructures will already mean a first step for progress. EU coordination and support to federate these e-infrastructures and further connections with Euro-HPC and EOSC services will contribute to build a common data infrastructure effective in managing the health-related big data and preparing the ground for a predictive, preventive, personalised and safe medicine. The establishment of a shared data and computation infrastructure, as well as pooling of scientific and medical expertise, is critical for Europe to benefit from the power of big data and analytics to offer citizens early diagnosis of diseases and new personalised treatments. This would lead to faster diagnosis of rare diseases (this will need cross-border data brought together), would allow for faster identification of and response to infectious diseases and would also allow for the development of personalised medicine. A European data and computation infrastructure could support access to large volumes of health-related data across borders based on which prevention, diagnosis and therapy development could be improved. 4. Digital tools for citizen empowerment and person-centred care 4.1. Challenges for health systems and the strive for affordable innovative solutions 4.1.1. Coping with an epidemic of chronic conditions The "Health at a Glance: Europe 2016" report revealed that across the EU deaths from major non-communicable diseases translate into around 3.4 million potentially productive life years lost, or EUR 115 billion in potential economic loss each year for the EU economies. Moreover, large health inequalities persist in EU Member States between people with higher levels of education and income and the more disadvantaged, largely due to different exposure to health risks, but also to disparities in health behaviour and access to high quality care. In addition to suffering and premature deaths, non-communicable diseases account for the vast bulk of the money spent by health and social systems. Up to 7% of GDP is unnecessarily lost due to the impact of non-communicable diseases that are, to a large extent, preventable. Many non-communicable diseases share the same behavioural risk factors: tobacco use, alcohol consumption, unhealthy diet, physical inactivity. According to recent estimations, more than 30% of the overall disease burden in the EU can be attributed to such risk factors.

Prevention of disease and promotion of healthy living are recognised as essential principles for reducing the health burden related to both communicable and non-communicable diseases, requiring cooperation across borders and coordination within the EU. Investing in health promotion and disease prevention can be cost-effective, yet EU Member States allocate only around 3% on average of their health budget to public health and prevention, according to "Health at a Glance: Europe 2016". Importantly, prevention comprises promotion of healthy lifestyles (individual lifestyle choices such as not smoking, eating healthy, avoiding alcohol and exercising more) underpinned by policy choices that help create school, work and community environments conducive to leading healthy lifestyles. The need to shift the focus from sickness and cure to promoting health and disease prevention, including combating health inequalities, is well recognised at national and EU level. It has been highlighted in the Joint Report on Health Care and Long-Term Care Systems and Fiscal Sustainability, as one of the recommended policy options to enhance the fiscal sustainability and cost-effectiveness of health systems. To face the challenges which non-communicable diseases pose to health systems, Member States have committed to reaching the voluntary targets of the United Nations/World Health Organisation on non-communicable diseases by 2025. The European Commission is committed to support Member States in reaching these goals which go hand in hand with Sustainable Development Goal 3 related to healthy lives and well-being for all at all ages, notably Goal 3.4 concerning non-communicable diseases, including mental health. The Member State Steering Group on Health Promotion and Prevention and Management of Non-Communicable Diseases provides strategic advice to the Commission and is a forum for consultation among Member States on the strategic planning in this area of health including the selection of best practices for transfer and scale-up within and across countries. This work is complemented by pertinent pan-EU collaborative actions, such as the joint actions on non-communicable diseases and healthy ageing "CHRODIS" (2013-2017) and "CHRODIS PLUS" (2017-2020) co-funded by the 3rd Health Programme. 4.1.2. People at the heart of reformed health and social care models The ageing of the population and rising prevalence of chronic conditions are increasing the demand for health and social care. This, combined with workforce shortages, is putting the standards of care and the sustainability of health and social care systems at risk. Member States and regional authorities are looking for innovative approaches to address these challenges and have been embarking on reforms of their health and long-term care systems, with the goal of achieving sustainable, effective and accessible care for all. These reforms aim at shifting care from hospital to primary, community and home settings, adopting person-centred approaches that integrate care, across the continuum of health and social care. In such reformed care models, the citizens, their families and informal caregivers have a significant role in the provision of healthcare together with care authorities. Firstly, an important element in person-centred care is that citizens become more involved in their care and engage in self-management of their well-being and health conditions. This is by participating actively in prescribed measures for health promotion, disease prevention, adherence to treatment and management of chronic conditions. In other words, citizens are empowered to support from their side the sustainability of health and social care systems. Secondly, citizens empowered in the way described above, can become a valuable "human resource" to health and social care systems. This is crucial considering the various issues regarding the workforce in health and social care, which have been identified for many years such as: challenges related to recruitment and retention of health and social care professionals, adverse demographic trends in workforce, difficult working conditions, lack of career perspectives for low-skilled health and social care staff, as well as the need for new skills in digital technologies and new roles in reformed care models. Finally, citizens can also help improve the quality of care, by having the possibility to provide healthcare professionals with feedback and health data related to their treatment or health condition. Such data, typically referred to as patient-reported experiences (PREMs) and patient-reported outcomes (PROMs) are of great relevance to patient-centred care and can present decision-makers with evidence to help them improve health outcomes and allocate resources more efficiently. An example can be found at the Martini Klinik in Germany, which specialises in prostatectomy and focuses on outcomes that matter to patients, not only to mortality reduction. The achieved results present a large improvement in patient-reported outcomes when compared to other hospitals in Germany; namely in cases of severe erectile dysfunction and incontinence. The EU Expert Group on Health Systems Performance Assessment has recommended that greater attention should be given to the assessment of patient experiences such as PREMs and PROMs. The Active and Assisted Living Joint Programme also provides important indicators to demonstrate the general benefit of involving users to meet real end-user needs and priorities in the innovation design processes, from idea creation to product testing and business model development. The projects in this programme adopt a multidisciplinary approach, including the close involvement of end-users at all stages of new solutions and product design. Users account for an average of 18% of project participants. This active user involvement determines actual user needs instead of merely guessing or generalising what makes the difference between a real innovation for users or a simply interesting technical development. It also lowers the barriers for large-scale deployment of ICT-based solutions. As indicated above, the digital transformation and new care models require health and care professionals to develop new skills and competences in a range of aspects: using digital technologies, devices and data; new roles, knowledge and techniques to support patients with multiple chronic conditions and to allow better health promotion and disease prevention; working in multi- and inter-disciplinary teams; and new ways of working to provide care at a distance. Without these, health system transformations, such as the one to digitally-supported person-centred care, are at risk due to resulting skills mismatches of health and care professionals. Equally important is the need for citizens and patients to improve their health and digital literacy in order to assume greater responsibility for their health and engage in self-care. 4.1.3 The role of digital solutions There is a growing body of evidence to support arguments that digital solutions can bring better health and care outcomes for citizens and contribute to improving the effectiveness, accessibility and resilience of health and care systems, when designed purposefully with the involvement of users and implemented on the basis of cost-effective criteria. This can be illustrated by the following examples: ·Health information portals, smartphones and mHealth apps empower citizens to take a more active role in looking after their health, change their health behaviours (within supportive environments) and engage in primary disease prevention. ·Digitally connected portable devices, sensors and apps can support patients in their adherence to treatments, managing their chronic conditions at their own home, and providing health data to their healthcare professionals as well as feedback on the quality of the health and care they receive. ·Electronic health records and telemedicine can facilitate the working conditions and the collaboration among health and social care professionals in delivery of integrated care services, also outside hospital settings, and can improve patient management as well as access of citizens to healthcare by overcoming geographical distances. Patient and user-generated health and care data are expected to further proliferate in the coming decade, creating continuously evolving and learning health systems. This could potentially disrupt the established status quo of health and social care delivery, opening up the ability to deliver more targeted health and social care services to citizens, and unlocking opportunities for new, data-driven economic models in public and consumer markets. Patient-reported outcomes have proven most effective if collected and processed through digital means. Advantages include simple and reliable data storage, enhanced mechanisms to improve completion by patients (as compared to non-digital PROMs) and better accessibility through customi