Five neuromuscular rare disease registries provide joint answers to questions from researchers or patients Proven interoperability

4 April 2023

Nijmegen, April 3, 2023 | Joint Press Release with ERN EURO-NMD: How many patients with rare neuromuscular disorders are there? How much time is there between the appearance of the first symptoms and the diagnosis of a rare disorder? These questions are highly relevant for patients but also difficult questions to answer. Most of the answers can be found in patient registries, but there are many different registries and, up to now, it was difficult to query these registries all at the same time. We now provide a proof-of-concept  demonstrating how five different rare disease registries for neuromuscular disorders can now be jointly queried because they are interoperable, announced Peter-Bram ‘t Hoen, Professor of Bioinformatics at Radboud University Medical Center.

Joint effort

This milestone was a joint effort from a number of partners building the registry hub for the European Reference Network on neuromuscular disorders under an EU-grant proposal: EURO-NMD. Because the registry hub connects different FAIR registries, it is now possible to conduct the same queries related to neuromuscular diseases in multiple, independent registries simultaneously without exposing sensitive patient details. The registries that participated in this proof-of-concept with mock data are: CRAMP (Computer Registry of All Myopathies and Polyneuropathies, Netherlands), DDP (Duchenne Data Platform, patient-led registry for Duchenne Muscular Dystrophy, Netherlands), DM-Scope (National registry for Myotonic Dystrophies, France), SMArtCARE (Clinical registry for Spinal Muscular Atrophy, Germany), and European Reference Network (EURO-NMD) registry. In order to support others in their FAIRification efforts, this demonstration prototype is publicly accessible in the Jupyter data analytics environment (https://github.com/markwilkinson/Duchenne-daru).

“We have made it easy for new FAIR registries to participate in joint analyses with other registries, answering questions around disease diagnosis, aetiology and progression. Patients can be assured that their data are being reused, in a secure manner, by scientists, clinicians, or other authenticated and authorised health professionals - which is their desire,” said Peter-Bram who is ERN EURO-NMD FAIRification and Interoperability Work Package Lead.

The FAIR principles

FAIR stands for Findable, Accessible, Interoperable, and Reusable. It is the acronym used to describe a global initiative to make data more valuable by increasing the ability of computers to find, interpret, integrate, and analyse those data autonomously. In this prototype, the computer calls a special Web address where specified and pre-approved queries (e.g. patient-count or phenotypic observations) are  executed inside the FAIR registry's secure space, and anonymized data are given back to the computer as output (see Figure). The prototype depends on a publicly available database of queries that were manually curated and filtered by experts in FAIR and neuromuscular diseases. FAIR makes it possible for the same query to be executed over independent resources, and thus sharing those queries leads to convergence between registries.

“One of the main ideas behind FAIR is for data to be both read, and ‘understood’, by machines. Achieving this has significant benefits for highly sensitive data, since it allows us to send machines into private data spaces to do the exploration and analysis for us, without needing to expose that data to a person.  This is what we demonstrated in this proof-of-concept: machines could execute complex analyses entirely on their own, over multiple patient registries, while keeping the sensitive data completely protected at all times.” - Mark D Wilkinson, co-Founder of FAIR Data Systems and lead-author of the original paper describing the FAIR Data Principles.

Next steps

The next steps are to increase the number and sophistication of the publicly available queries - all reviewed for security by both technical and rare disease experts - in the demonstration prototype. In addition, plans are in place to create an interface for patients with Duchenne and Becker Muscular Dystrophy to ask questions that matter to them such as ‘How many people have the same symptoms as me?’. The proof-of-concept will make it possible to send this question or ‘query’ across other FAIR registries within the ERN EURO-NMD registry Hub, with a reach of an estimated 100,000 patients with neuromuscular diseases. Up-to-date and instant results will be received automatically which saves time and valuable resources. This ultimately, helps inform patients on issues that are important to them as well as speed-up progress towards earlier diagnosis and innovative treatments. At Radboudumc we’re proud to be involved in these meaningful FAIR efforts alongside the rare disease community.

“The quote by Nelson Mandela, ‘It always seems impossible until it’s done’ couldn’t be more appropriate in achieving this milestone. Managing five different teams and the FAIR experts required focus, resilience, flexibility, and an incredible determination by everyone involved. Prototypes work wonders in ‘showing’ various stakeholders how we’re creating impact with FAIR data. Today, we‘re being assisted by machines to access high volume data, stored in different locations and get answers to specific validated predefined questions, all automatically within seconds,” explained Nawel Lalout, FAIR Data Stewards at Radboudumc who coordinated these efforts to completion.

 

Figure 1. Schematic representation of privacy-promoting federation of multiple independent registries. On demand searches are performed over FAIR datasets via a search interface. All this is protected by a "proxy," which further isolates the other components and ensures only encrypted communication over the Web. For example, access to the proxy retrieves only a count of patients with a rare disease, which can be aggregated in a graphical analysis environment. [Abbreviations: API, Application Programming Interface; FDP, FAIR data point; EJPRD, European Joint Program for Rare Diseases]

For more information, please contact Nawel Lalout, FAIR Data Steward at Radboudumc: nawel.lalout@radboudumc.nl.

About ERN EURO-NMD

EURO-NMD is a European Reference Network (ERN) that aims to harmonise and implement best practices for clinical and diagnostic procedures for rare neuromuscular diseases across all European Union member states. EURO-NMD, the ERN for Rare Neuromuscular Diseases, spans 24 European countries and includes 85 reference centres. EURO-NMD oversees more than 100,000 patients with rare neuromuscular conditions. The Network members are committed to collaborating closely to improve the health outcomes of their paediatric and adult patients with rare neuromuscular disorders. Core objectives of the collaboration are the implementation of clinical practice guidelines and the definition and prospective monitoring of core indicators of guideline conforming management, treatment quality and patient health outcomes. Visit https://ern-euro-nmd.eu.

 

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