Evidentiary basis of the first regulatory qualification of a digital primary efficacy endpoint

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.

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Publication Details

Journal
Scientific Reports
Published
2024-11-29
DOI
https://doi.org/10.1038/s41598-024-80177-9
Citations
18
Primary Topic
Muscle Physiology and Disorders
Type
article
Field-Weighted Citation Impact
4.21

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article

Evidentiary basis of the first regulatory qualification of a digital primary efficacy endpoint

Maitea Guridi Ormazabal, Stefano Carlo Previtali, A. Seferian, Valeria Sansone et al.
18 citations
Scientific Reports
Muscle Physiology and Disorders
4.21
article

Evidentiary basis of the first regulatory qualification of a digital primary efficacy endpoint

Maitea Guridi Ormazabal, Stefano Carlo Previtali, A. Seferian, Valeria Sansone, Volker Straub, Pat Furlong, Nina Butoianu, Mariacristina Scoto, Jessica Braid, Paul Strijbos, Ulrike Schara‐Schmidt, Eugenio Maria Mercuri, Nathalie Goemans, Teji Singh, M. Tulinius, A. Nascimento, Laurent Servais, M. Annoussamy, Carole Vuillerot, Roxana Donisa Dreghici, Damien Eggenspieler, Margaux Poleur, Francesco Muntoni, A Tricot, Andrada Mirea
article en
18 citations

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.

Scientific ReportsVol. 14(1)
Université Claude Bernard Lyon 1 (FR), Università Cattolica del Sacro Cuore (IT), Roche (Switzerland) (CH), Hospital Sant Joan de Déu Barcelona (ES), University of Liège (BE), Carol Davila University of Medicine and Pharmacy (RO), University of Milan (IT), Great Ormond Street Hospital (GB), Newcastle upon Tyne Hospitals NHS Foundation Trust (GB), Agostino Gemelli University Polyclinic (IT), Sorbonne Université (FR), University of Oxford (GB), Hôpital Femme Mère Enfant (FR), Hôpital Armand-Trousseau (FR), Center for Children (US), Hospices Civils de Lyon (FR), Parent Project Muscular Dystrophy (US), Centro Clinico Nemo (IT), Sysnav (France) (FR), Roche (United Kingdom) (GB), Institut NeuroMyoGène (FR), IRCCS Ospedale San Raffaele (IT), Hôpital Mère-Enfant (FR), Oxford BioMedica (United Kingdom) (GB), Sarepta Therapeutics (United States) (US), Solidus Biosciences (United States) (US), Centre hospitalier régional de la Citadelle (BE), Institut de Recerca Sant Joan de Déu, University College London (GB), Newcastle University (GB), University of Gothenburg (SE), KU Leuven (BE)
F. Hoffmann-La Roche
Openalex Percentile: Top 5%
Muscle Physiology and Disorders
4.21
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