The ARCA registry: a collaborative global platform for advancing trial readiness in autosomal recessive cerebellar ataxias
Creators: name: Traschütz, Andreas
name: Reich, Selina
name: Adarmes, Astrid D.
name: Anheim, Mathieu
name: Ashrafi, Mahmoud Reza
name: Baets, Jonathan
name: Basak, A. Nazli
name: Bertini, Enrico
name: Brais, Bernard
name: Gagnon, Cynthia
name: Gburek-Augustat, Janina
name: Hanagasi, Hasmet A.
name: Heinzmann, Anna
name: Horvath, Rita
name: De Jonghe, Peter
name: Kamm, Christoph
name: Klivenyi, Peter
name: Klopstock, Thomas
name: Minnerop, Martina
name: Münchau, Alexander
name: Renaud, Mathilde
name: Roxburgh, Richard H.
name: Santorelli, Filippo M.
name: Schirinzi, Tommaso
name: Sival, Deborah A.
name: Timmann, Dagmar
name: Vielhaber, Stefan
name: Wallner, Michael
name: Van De Warrenburg, Bart P.
name: Zanni, Ginevra
name: Zuchner, Stephan
name: Klockgether, Thomas
name: Schüle, Rebecca
name: Schöls, Ludger
name: Synofzik, Matthis
Publisher: name: Universität Ulm
Year: 2021
Subjects: subject: registry
subject: network
subject: trial readiness
subject: DDC 570 / Life sciences
subject: DDC 610 / Medicine &amp; health
subject: Ataxia
subject: Natural history
subject: Ataxie
subject: Naturgeschichte (Fach)

description: Autosomal recessive cerebellar ataxias (ARCAs) form an ultrarare yet expanding group of neurodegenerative multisystemic diseases affecting the cerebellum and other neurological or non-neurological systems. With the advent of targeted therapies for ARCAs, disease registries have become a precious source of real-world quantitative and qualitative data complementing knowledge from preclinical studies and clinical trials. Here, we review the ARCA Registry, a global collaborative multicenter platform (&gt;15 countries, &gt;30 sites) with the overarching goal to advance trial readiness in ARCAs. It presents a good clinical practice (GCP)- and general data protection regulation (GDPR)-compliant professional-reported registry for multicenter web-based capture of cross-center standardized longitudinal data. Modular electronic case report forms (eCRFs) with core, extended, and optional datasets allow data capture tailored to the participating site's variable interests and resources. The eCRFs cover all key data elements required by regulatory authorities [European Medicines Agency (EMA)] and the European Rare Disease (ERD) platform. They capture genotype, phenotype, and progression and include demographic data, biomarkers, comorbidity, medication, magnetic resonance imaging (MRI), and longitudinal clinician- or patient-reported ratings of ataxia severity, non-ataxia features, disease stage, activities of daily living, and (mental) health status. Moreover, they are aligned to major autosomal-dominant spinocerebellar ataxia (SCA) and sporadic ataxia (SPORTAX) registries in the field, thus allowing for joint and comparative analyses not only across ARCAs but also with SCAs and sporadic ataxias. The registry is at the core of a systematic multi-component ARCA database cluster with a linked biobank and an evolving study database for digital outcome measures. Currently, the registry contains more than 800 patients with almost 1,500 visits representing all ages and disease stages; 65% of patients with established genetic diagnoses capture all the main ARCA genes, and 35% with unsolved diagnoses are targets for advanced next-generation sequencing. The ARCA Registry serves as the backbone of many major European and transatlantic consortia, such as PREPARE, PROSPAX, and the Ataxia Global Initiative, with additional data input from SPORTAX. It has thus become the largest global trial-readiness registry in the ARCA field.