Heart-Core Registry: background and introduction

Between 5000 and 8000 rare diseases affect the daily lives of around 30 million persons in the EU. Because of the low number of patients per disease and per EU Member State, detailed knowledge about the underlying pathophysiology and natural course is lacking for the majority of these diseases. As a result, appropriate diagnostic tools, therapies and risk stratification strategies are not always available. No country alone has the knowledge and capacity to treat all types of rare, low-prevalence or complex conditions and diseases. Cooperation at European level makes therefore a real difference to rare diseases patients and their families, as well as the healthcare professionals helping them. By cooperating and exchanging life-saving knowledge in the ERNs, expert HCPs across Europe provide access to a much larger pool of expertise. By connecting experts and patient populations, ERNs have the potential to build large registries of patients affected with rare, low-prevalence or complex diseases. Such registries at European level can serve as powerful data sources for clinicians and researchers to develop research projects and clinical trials and better understand the natural history of diseases to discover novel diagnostic, therapeutic and risk stratification tools. In addition, rare disease registries may support policy makers at both national and European level to better monitor public health and improve healthcare management. The importance of rare disease registries has been recognized previously by the EU in a document called “EU Council Recommendation of 8 June 2009 on an action in the field of rare diseases”. Moreover, patient registries support the activities of ERNs to (according to Directive 2011/24/EU) “make a contribution to research”.

Currently, there are more than nearly 800 rare disease registries in Europe. However, extreme fragmentation exists across these rare disease registries with different objectives, data collection methods, and little standardization in governance models. These heterogeneities between the European rare disease registries and their lack of interoperability severely limits their potential. Harmonizing data models and increasing interoperability among rare diseases registries, particularly those used and enhanced by ERNs, will help ERNs to share data, boost economies of scale and ensure a more efficient use of resources.

To reach its goal 5 and comply with the requirement set out in Directive 2011/24/EU (“make a contribution to research”), ERN GUARD-Heart has contributed to build 7 condition (disease- or gene-specific) registries of patients with rare cardiac conditions or diseases. These registries encompass the entire scope of the ERN GUARD-Heart, including its current 3 thematic areas. The ERN GUARD-Heart patients registries include:

  1. International registry of patients with a variant in the CALM genes.
  2. International registry of catecholaminergic polymorphic ventricular tachycardia.
  3. International registry of long QT syndrome.
  4. International registry of short QT syndrome.
  5. International registry of patients with a variant in the PRKAG2 gene.
  6. International registry of long QT syndrome type 5 (KCNE1 gene)
  7. International registry of arrhythmogenic right ventricular cardiomyopathy.

These registries are web-based (REDCap) and accessible to all members of the Network. Data from these registries have been successfully used for several research projects studying the natural course of conditions, therapy options and effectiveness, and clinical outcomes. Results of these research projects have been published in high-ranked peer-reviewed scientific journals. However, due to lack of resources, ERN GUARD-Heart registries do not optimally apply existing approaches and tools for semantic interoperability. For example, data in the registries have been only partially aligned with available international standards, for example standards and ontologies provided by the European Commission’s Joint Research Centre and the Orphanet Rare Disease Ontology (ORDO). Alignment of registry data with standards through the use of common data elements, data structures, terminologies and ontologies has been recognized as a quality indicator which reflects consistency, reusability and semantic interoperability. The lack of semantic interoperability with other rare disease registries limits the potential of ERN GUARD-Heart registries for stakeholders (e.g.., policy makers, patients, other ERNs) to be used for policy making, healthcare monitoring and management, epidemiological studies, (meta)data sharing, or comparisons with other registries.

The main objective of the Heart-Core Registry project is to develop a comprehensive approach for rare disease registration in ERN GUARD-Heart by establishing the first overarching registry of ERN GUARD-Heart (i.e., the Heart-Core Registry) using standards and tools provided by the European Platform on Rare Disease Registration (EU RD Platform). To harmonize data and facilitate semantic interoperability, in the Heart-Core Registry a minimal dataset (including the Set of Common Data Elements for Rare Diseases Registration provided by the European Commission’s Joint Research Centre) will be prospectively collected for new patients in the ongoing ERN GUARD-Heart registries (numbers 1, 2, 4 and 5 above) and in future ERN GUARD-Heart registries. In addition, the Heart-Core Registry will signpost users to the detailed disease- or gene-specific ERN GUARD-Heart registries. To render its data more searchable and findable, the Heart-Core Registry will be registered on the European Rare Disease Registry Infrastructure (ERDRI). It is expected that the activities proposed in this application will facilitate ERN GUARD-Heart to reach its goals and specific objectives, create a cost-effective and comprehensive approach of rare disease registration in the ERN GUARD-Heart, lead to increased awareness of ERN GUARD-Heart patient registries and improved reusability of data in these registries among various stakeholders, and enable better interaction among rare disease registries in Europe.