Patient registries are increasingly recognized as a powerful tool for assessing disease course, understanding variations in diagnosis, treatment and outcomes, and investigating factors affecting prognosis and quality of life. On the other hand, patient registries often cover only individual diseases or groups of diseases, have different standards of data quality or are subject to commercial interests. The diversity of the registry landscape with its inconsistent structures leads to a great time burden for the health care providers with sometimes duplicated efforts.
The Unified European registry for Inherited Metabolic Diseases is the first observational, non-interventional patient registry established by academia that encompasses all 1,400+ IMDs. Eighteen months after the official initiation the registry comprises already data on more than 1100 IMD patients from 14 MetabERN partners and one non-MetabERN partner in 9 European countries.
By implementing the ERDRI requirements in the U-IMD registry full semantic interoperability for other IMD registries has been achieved. Using the iNTD registry, an existing registry for individuals with neurotransmitter-associated IMDs started in 2014, as a pilot we established a template to upgrade existing IMD registries improving their semantic interoperability and complying with ERDRI. Similarly, the cooperation between U-IMD and ERKNet was successfully documented by using a core dataset.
It is expected that the continuation of this positive development will lead to a better understanding of the long-term course of the disease and the outcome as well as a clear identification of disease variants for IMD. Furthermore, it will enable an evaluation of genotype/phenotype correlations, and an optimization of diagnostic and therapeutic strategies, which in the long run will not only shorten the diagnostic odyssey of patients but also improve the long-term clinical outcomes of affected patients.
The ethical review process required for the assessment of longitudinal patient data needs to be regarded as a major drawback for the activation process of individual sites and, as a consequence, for patient recruitment. For data sharing within or between ERNs a consent form has been developed (https://cpms-training.ern-net.eu/cms/media/consent/EN_Informed Consent.pdf). By signing the form, patients and parents agree to share data collected at their hospital with other ERN healthcare professionals. Such data may include medical images or reports and laboratory reports and would provide therefore offer an ideal basis for data collection within a patient registry. However, the ERN Patient Consent Form for Data Sharing has found to be insufficient for the use with U-IMD registry (and analogous projects), since the evaluation of the patient registry has to be regarded as research and therefore has to follow the EU General Data Protection Regulation (EU-GDPR, https://ec.europa.eu/info/law/law-topic/data-protection_en, Enforced since 25.05.2018). Any research study that aims to evaluate and publish data requires a separate ethic approval and informed consent process.
Since there are no agreed rules for low or even no risk non-interventional or observational research studies on European level, the ethical review process is laborious and bureaucratic for U-IMD centres in some countries. For future projects under the umbrella of a European Reference Networks it would therefore be of great benefit to harmonize regulations for the ethical review process. In addition, a standardized consent form that would allow ERN healthcare professionals to make available and share patient data stored in healthcare records would ensure data extraction, exchange, and cross-site analysis between databases, registries or research projects in a GDPR-protected framework.
Platform for clinical research and trial
The data gathered in the U-IMD registry is pseudonymized by using the EUPID service. Members can only access their own patient data and always retain full data ownership. Usage of the entire U-IMD dataset is governed by the U-IMD Consortium, granting members equal rights in initiating and deciding on mutual projects. Any member may make specific and sufficiently elaborated requests to the Members Board to use the network’s data for clinical research. In addition, for describing the natural course of IMDs or other related clinical research, the U-IMD registry can serve as an excellent platform for the screening of patient cohorts and the organization of clinical research studies and trials. In the context of the recent increase in innovative and partially individualized treatments, such patient registries can also provide detailed safety and efficacy monitoring after drug approval. It hereby contributes to a facilitated approval of orphan drugs.
Outlook and participation
U-IMD has established a European registry for all known IMDs. By strictly following ERDRI standards the U-IMD registry is well suited to cooperate with existing or newly established resources in the field of rare diseases, such as databases or platforms. Through semantic interoperability, it also provides a basis for machine learning or the use of other advanced digital tools including artificial intelligence AI algorithms. Hereby, even for rare diseases a significant shortening of the path to diagnosis could be achieved in future. U-IMD is collaborating in the context of ERDRI, Solve-RD and EJP-RD to make its datasets a findable asset that could be merged with compatible datasets, using the EUPID and RD-NEXUS services. Being the official registry of MetabERN it is also open to all European and international health care providers, following individuals with IMDs. Supporting information and material can be obtained by contacting U-IMD via the project or registry website.