Comparing randomized trial designs to estimate treatment effect in rare diseases with longitudinal models: a simulation study showcased by Autosomal Recessive Cerebellar Ataxias using the SARA score.

ABSTRACT: Parallel designs with an end-of-treatment analysis are commonly used for randomised trials, but they remain challenging to conduct in rare diseases due to small sample size and heterogeneity. A more powerful alternative could be to use model-based approaches. We investigated the performance of longitudinal modelling to evaluate disease-modifying treatments in rare diseases using simulations. Our setting was based on a model describing the progression of the standard clinician-reported outcome SARA score in patients with ARCA (Autosomal Recessive Cerebellar Ataxia), a group of ultra-rare, genetically defined, neurodegenerative diseases. We performed a simulation study to evaluate the influence of trials settings on their ability to detect a treatment effect slowing disease progression, usin

SUBMITTER: Hendrickx N 

PROVIDER: S-EPMC12309037 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature