Rare Disease Registries Are Key to Evidence-Based Personalized Medicine: Highlighting the European Experience

Abstract

Rare diseases, such as inherited metabolic diseases, have been identified as a health priority within the European Union more than 20 years ago and have become an integral part of EU health programs and European Reference Networks. Having the potential to pool data, to achieve sufficient sample size, to overcome the knowledge gap on rare diseases and to foster epidemiological and clinical research, patient registries are recognized as key instruments to evidence-based medicine for individuals with rare diseases. Patient registries can be used for multiple purposes, such as (1) describing the natural history and phenotypic diversity of rare diseases, (2) improving case definition and indication to treat, (3) identifying strategies for risk stratification and early prediction of disease severity (4), evaluating the impact of preventive, diagnostic, and therapeutic strategies on individual health, health economics, and the society, and (5) informing guideline development and policy makers. In contrast to clinical trials, patient registries aim to gather real-world evidence and to achieve generalizable results based on patient cohorts with a broad phenotypic spectrum. In order to develop a consistent and sustained framework for rare disease registries, uniform core principles have been formulated and have been formalized through the European Rare Disease Registration Infrastructure. Adherence to these core principles and compliance with the European general data protection regulations ensures that data collected and stored in patient registries can be exchanged and pooled in a protected environment. To illustrate the benefits and limitations of patient registries on rare disease research this review focuses on inherited metabolic diseases.

Licensing of Orphan Medicinal Products—Use of Real-World Data and Other External Data on Efficacy Aspects in Marketing Authorization Applications Concluded at the European Medicines Agency Between 2019 and 2021

“…This approach may not be applicable across all disease types, but may still provide valuable information, for example, on sample size considerations or the need for standardization in the setting of a subsequent trial. The creation of the European Reference Network of Disease Registries on rare diseases and the associated more systematic data collection according to sub-specialties hold, therefore, the most promise for improving the efficiency of clinical trials in the future (Kölker et al, 2022).…”

Hereditary Colorectal Cancer Syndromes Registry: What, How, and Why?

“…There has been much data regarding the importance of rare disease registries. 17,22,23 An inherited colorectal cancer registry will improve the quality of care for patients and will be a source of academic productivity and organizational health care integration.…”

How longitudinal observational studies can guide screening strategy for rare diseases

“…However, despite this obvious need, and because of their high costs, longitudinal observational studies have remained the neglected part of NBS programs. Formal evidence of the clinical effectiveness and long‐term benefits of MS/MS‐based NBS in large cohorts with longer follow‐up, 42,43,50–52 cross‐sectional analysis of patient registries managed by transnational scientific consortia, 53–59 or from meta‐analysis 60 is still scarce. Current knowledge is mostly based on short‐term follow‐up of small‐ or medium‐sized regional cohorts 51,61–69 .…”