Tracking individual disease-trajectory of patients with neuromuscular disorders (Duchenne muscular dystrophy and spinal muscular atrophy)

Neuromuscular diseases represent a diverse group of complex genetic disorders. In conditions such as Duchenne muscular dystrophy (DMD) and Spinal muscular atrophy (SMA), progressive motor impairment limiting activities of daily life is a common and central clinical feature. Over the last 15 years, the emergence of clinical trials and the approval of new therapies have transformed the disease landscape. A consistent theme across these conditions is the reliance on motor clinical outcome measures, which play a crucial role in guiding treatment decisions and assessing research outcomes. The development of disease-specific outcome measures, along with the use of wearable technologies to monitor motor function, has expanded the possibilities for evaluation. Quantifying progressive motor decline is key to supporting prognosis and informing both care decisions and clinical trial endpoints. However, selecting appropriate and fit-for-purpose outcome measures is essential to ensure accurate interpretation of findings. This thesis critically examined three publications, all focused on motor outcome measures. The first explores the use of a wearable device that records gait in an uncontrolled environment for use in clinical trials. The second identifies prognostic factors from a longitudinal natural history study in DMD. The third highlights the value of incorporating patient-reported outcome measures alongside motor assessments. Guided by the International Classification of Functioning (ICF) framework, this work aims to critically assess motor outcome measures to enhance our understanding of disease progression tracking in DMD and SMA. The analysis concludes that no single motor outcome measure can fully capture disease progression or treatment effects, underscoring the need to combine multiple tools alongside consideration of statistical analysis in the context of rare diseases. It also highlights that defining “meaningful change” depends on context and rater type, making stakeholder involvement essential for ensuring clinical relevance and advancing patient-centred care.

Grantor dc:publisher

Oxford Brookes University

Author dc:creator

• Lilien, Charlotte

Contributors dc:contributor

• Collett, Johnny

Statement dc:rights

• All rights reserved

Language dc:language

en

DOI dc:identifier

https://doi.org/10.24384/24f9-wq28

OAI identifier oai:identifier

tle:cd35daf2-ff1b-4774-b6e3-53fee6170ff0:d6bd9758-527a-46cd-bfe2-c433766e8fca:1