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)...

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Detalhes bibliográficos
Autores: Servais L, Strijbos P, Poleur M, Mirea A, Butoianu N, Sansone VA, Vuillerot C, Schara-Schmidt U, Scoto M, Seferian AM, Previtali SC, Tulinius M, Nascimento A, Furlong P, Singh T, Dreghici RD, Goemans N, Mercuri E, Straub V, Ormazabal MG, Braid J, Muntoni F, Tricot A, Annoussamy M, Eggenspieler D
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2024
País:España
Recursos:Fundació Sant Joan de Déu
Repositório:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p27081
Acesso em linha:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=27081
Access Level:Acceso aberto
Palavra-chave:Stride Velocity 95th Centile
Digital endpoints
Wearables
Duchenne muscular dystrophy
Regulatory qualification
V3 framework
Descrição
Resumo: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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