Evidentiary basis of the first regulatory qualification of a digital primary efficacy endpoint
Year: 2024
Type: article
Abstract: Stride velocity 95th centile (SV95C) is a wearable-derived endpoint representing the 5% fastest strides taken during everyday living. In July 2023, SV95C received European Medicines Agency (EMA) qualification for use as a primary endpoint in trials of patients with Duchenne muscular dystrophy (DMD) aged ≥ 4 years-becoming the first digital endpoint to receive such qualification. We present the data supporting this qualification, providing insights into the evidentiary basis of qualification as a digital clinical outcome assessment. Clinical trials, natural history studies, and patient surveys (ages 5 - 14 years) showed that SV95C is accurate, valid, reliable, sensitive, and clinically meaningful. SV95C significantly correlated with traditional DMD assessments, increased rapidly after steroid initiation (0.090 m/s 3 months post-treatment), and declined steadily in patients on stable steroid regimens. Compared with traditional assessments, SV95C demonstrated earlier sensitivity to disease progression (3 vs 9 months) and greater sensitivity at 12 months. Distribution- and anchor-based approaches revealed a change of - 0.10 to - 0.20 m/s as clinically meaningful. The EMA qualification of SV95C illustrates the willingness of regulators to accept novel digital endpoints for drug approval, setting an important precedent for the evidentiary basis of regulatory digital endpoint qualification that could transform clinical development in disorders affecting movement.
Source: Scientific Reports
Authors: Laurent Servais, Paul Strijbos, Margaux Poleur, Andrada Mirea, Nina Butoianu, Valeria A. Sansone, Carole Vuillerot, Ulrike Schara-Schmidt, Mariacristina Scoto, Andreea M. Seferian, Stefano C. Previtali, Már Tulinius, Andrés Nascimento, Pat Furlong, Teji Singh, Roxana Donisa Dreghici, Nathalie Goemans, Eugenio Mercuri, Volker Straub, Maitea Guridi Ormazabal, Jessica Braid, Francesco Muntoni, Alexis Tricot, Mélanie Annoussamy, Damien Eggenspieler
Institutions: University of Liège, University of Oxford, NIHR Oxford Biomedical Research Centre, Centre Hospitalier Universitaire de Liège, Roche (Switzerland), Centre hospitalier régional de la Citadelle, Carol Davila University of Medicine and Pharmacy, University of Milan, Centro Clinico Nemo, Université de Lyon, Hospices Civils de Lyon, Institut NeuroMyoGène, University of Duisburg-Essen, NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, Hôpital Armand-Trousseau, IRCCS Ospedale San Raffaele, Drottning Silvias barn- och ungdomssjukhus, University of Gothenburg, Hospital Sant Joan de Déu Barcelona, Institut de Recerca Sant Joan de Déu, Parent Project Muscular Dystrophy, Sarepta Therapeutics (United States), Universitair Ziekenhuis Leuven, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle University, Roche (United Kingdom)
Language: English
Subfield: Statistics and Probability
Field: Mathematics
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,590
Funder: F. Hoffmann-La Roche
OpenAlex ID: W4404865431