Assessment of fatigability in patients with spinal muscular atrophy: development and content validity of a set of endurance tests

Bart Bartels, Laura E Habets, Marloes Stam, Renske I Wadman, Camiel A Wijngaarde, Marja A G C Schoenmakers, Tim Takken, Erik H J Hulzebos, W Ludo van der Pol, Janke F de Groot, Bart Bartels, Laura E Habets, Marloes Stam, Renske I Wadman, Camiel A Wijngaarde, Marja A G C Schoenmakers, Tim Takken, Erik H J Hulzebos, W Ludo van der Pol, Janke F de Groot

Abstract

Background: Fatigability has emerged as an important dimension of physical impairment in patients with Spinal Muscular Atrophy (SMA). At present reliable and valid outcome measures for both mildly and severely affected patients are lacking. Therefore the primary aim of this study is the development of clinical outcome measures for fatigability in patients with SMA across the range of severity.

Methods: We developed a set of endurance tests using five methodological steps as recommended by the 'COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). In this iterative process, data from multiple sources were triangulated including a scoping review of scientific literature, input from a scientific and clinical multidisciplinary expert panel and three pilot studies including healthy persons (N = 9), paediatric patients with chronic disorders (N = 10) and patients with SMA (N = 15).

Results: Fatigability in SMA was operationalised as the decline in physical performance. The following test criteria were established; one method of testing for patients with SMA type 2-4, a set of outcome measures that mimic daily life activities, a submaximal test protocol of repetitive activities over a longer period; external regulation of pace. The scoping review did not generate suitable outcome measures. We therefore adapted the Endurance Shuttle Walk Test for ambulatory patients and developed the Endurance Shuttle Box and Block Test and the - Nine Hole Peg Test for fatigability testing of proximal and distal arm function. Content validity was established through input from experts and patients. Pilot testing showed that the set of endurance tests are comprehensible, feasible and meet all predefined test criteria.

Conclusions: The development of this comprehensive set of endurance tests is a pivotal step to address fatigability in patients with SMA.

Keywords: Endurance; Fatigability; Outcome measure; Spinal muscular atrophy.

Conflict of interest statement

Ethics approval and consent to participate

The Medical Ethics Committee of the University Medical Centre Utrecht in the Netherlands approved the research protocol. Written informed consent was obtained from all subjects and their parents.

Consent for publication

Written consent for publication was obtained from all subjects and their parents with regards to images used.

Competing interests

The employer of author Bart Bartels has received ad hoc consultancy fees from Scholar Rock and Cytokinetics (scientific advisory boards) and Biogen (speaker activity scientific conference). The employer of author Ludo van der Pol has received ad hoc consultancy fees from Biogen and Avexis (scientific advisory boards) and from Novartis (data monitoring committee). The remaining authors have no conflicts of interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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