Item performance of the scale for the assessment and rating of ataxia in rare and ultra‐rare genetic ataxias

Hamdan, Alzahra; Hooker, Andrew C.; Chen, Xiaomei; Traschütz, Andreas; Schüle, Rebecca; ,; ,; Synofzik, Matthis; Karlsson, Mats O.

doi:10.1002/psp4.13162

Cited by 2 publications

References 38 publications

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Assessment of the Reliability, Responsiveness, and Meaningfulness of the Scale for the Assessment and Rating of Ataxia (SARA) for Lysosomal Storage Disorders

Park,

Bremova-Ertl,

Brands

et al. 2024

Preprint

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Objective To evaluate the reliability, responsiveness, and validity of the Scale for the Assessment and Rating of Ataxia (SARA) in patients with Lysosomal Storage Disorders (LSDs) who present with neurological symptoms and quantify the threshold for a clinically meaningful change. Methods We analyzed data from three clinical trial cohorts (IB1001-201, IB1001-202, IB1001-301) of patients with Niemann-Pick disease type C (NPC) and GM2 Gangliosidoses (Tay-Sachs and Sandhoff disease) comprising 122 patients and 703 visits. Reproducibility was described as retest reliability between repeat baseline visits or baseline vs. post-treatment washout visits. Responsiveness was determined in relation to the Investigator, Caregiver, and Patient Clinical Global Impression of Improvement (CGI-I). The CGI-I data was also used to quantify a threshold for a clinically meaningful improvement on the SARA scale. Using a qualitative methods approach, patient/caregiver interviews from the IB1001-301 trial were further used to assess a threshold of meaningful change as well as the breadth of neurological signs and symptoms captured and evaluated by the SARA scale. Results The Inter-Class Correlation (ICC) was 0.95 or greater for all three trials, indicating a high internal consistency/reliability. The mean change in SARA between repeat baseline or post-treatment washout visit assessments in all trials was -0.05, SD 1.98, i.e. minimal, indicating no significant differences, learning effects or other systematic biases. For the CGI-I responses and change in SARA scores Area Under the Curve (AUC) values were 0.82, 0.71, and 0.77 for the Investigator, Caregiver, and Patient CGI-I respectively, indicating strong agreement. Further qualitative analyses of the patient/caregiver interviews demonstrated a 1-point or greater change on SARA to be a clinically meaningful improvement which is directly relevant to the patients' everyday functioning and quality of life. Changes captured by the SARA were also paralleled by improvement in a broad range of neurological signs and symptoms and beyond cerebellar ataxia. Conclusion Qualitative and quantitative data demonstrate the reliability and responsiveness of the SARA score as a valid measure of neurological signs and symptoms in LSDs. A 1-point change represents a clinically meaningful transition reflecting the gain or loss of complex function.

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Assessment of the Reliability, Responsiveness, and Meaningfulness of the Scale for the Assessment and Rating of Ataxia (SARA) for Lysosomal Storage Disorders

Park,

Bremova-Ertl,

Brands

et al. 2024

Preprint

Self Cite

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Prediction of Individual Disease Progression Including Parameter Uncertainty in Rare Neurodegenerative Diseases: The Example of Autosomal-Recessive Spastic Ataxia Charlevoix Saguenay (ARSACS)

Hendrickx,

Mentré,

Traschütz

et al. 2024

AAPS J

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The aim of this study was to develop a model to predict individual subject disease trajectories including parameter uncertainty and accounting for missing data in rare neurological diseases, showcased by the ultra-rare disease Autosomal-Recessive Spastic Ataxia Charlevoix Saguenay (ARSACS). We modelled the change in SARA (Scale for Assessment and Rating of Ataxia) score versus Time Since Onset of symptoms using non-linear mixed effect models for a population of 173 patients with ARSACS included in the prospective real-world multicenter Autosomal Recessive Cerebellar Ataxia (ARCA) registry. We used the Multivariate Imputation Chained Equation (MICE) algorithm to impute missing covariates, and a covariate selection procedure with a pooled p-value to account for the multiply imputed data sets. We then investigated the impact of covariates and population parameter uncertainty on the prediction of the individual trajectories up to 5 years after their last visit. A four-parameter logistic function was selected. Men were estimated to have a 25% lower SARA score at disease onset and a moderately higher maximum SARA score, and time to progression (T50) was estimated to be 35% lower in patients with age of onset over 15 years. The population disease progression rate started slowly at 0.1 points per year peaking to a maximum of 0.8 points per year (at 36.8 years since onset of symptoms). The prediction intervals for SARA scores 5 years after the last visit were large (median 7.4 points, Q1-Q3: 6.4–8.5); their size was mostly driven by individual parameter uncertainty and individual disease progression rate at that time. Graphical Abstract

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Item performance of the scale for the assessment and rating of ataxia in rare and ultra‐rare genetic ataxias

Cited by 2 publications

References 38 publications

Assessment of the Reliability, Responsiveness, and Meaningfulness of the Scale for the Assessment and Rating of Ataxia (SARA) for Lysosomal Storage Disorders

Assessment of the Reliability, Responsiveness, and Meaningfulness of the Scale for the Assessment and Rating of Ataxia (SARA) for Lysosomal Storage Disorders

Prediction of Individual Disease Progression Including Parameter Uncertainty in Rare Neurodegenerative Diseases: The Example of Autosomal-Recessive Spastic Ataxia Charlevoix Saguenay (ARSACS)

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