In people with young onset Parkinson’s disease (YOPD), onset of symptoms is between 21 and 40 years of age. The distinction between YOPD and late-onset Parkinson’s disease is supported by genetic differences (a genetic etiology is more common in people with YOPD) and clinical differences (e.g., dystonia and levodopa-induced dyskinesias are more common inYOPD). Moreover, people with YOPD tend to have different family and societal engagements compared to those with late-onset PD. These unique features have implications for clinical management, and call for a tailored multidisplinary approach involving shared-decision making.
This study characterizes the speech phenotype of spinocerebellar ataxia type 1 (SCA1) using both perceptual and objective acoustic analysis of speech in a cohort of SCA1 patients. Twenty-seven symptomatic SCA1 patients in various disease stages (SARA score range: 3–32 points) and 18 sex and age matched healthy controls underwent a clinical assessment addressing ataxia severity, non-ataxia signs, cognitive functioning, and speech. Speech samples were perceptually rated by trained speech therapists, and acoustic metrics representing speech timing, vocal control, and voice quality were extracted. Perceptual analysis revealed reduced intelligibility and naturalness in speech samples of SCA1 patients. Acoustically, SCA1 patients presented with slower speech rate and diadochokinetic rate as well as longer syllable duration compared to healthy controls. No distinct abnormalities in voice quality in the acoustic analysis were detected at group level. Both the affected perceptual and acoustic variables correlated with ataxia severity. Longitudinal assessment of speech is needed to place changes in speech in the context of disease progression and potential response to treatment.
Objective
There currently is no disease-modifying therapy for spinocerebellar ataxia type 1 (SCA1). Genetic interventions, such as RNA-based therapies, are being developed but those currently available are very expensive. Early evaluation of costs and benefits is, therefore, crucial. By developing a health economic model, we aimed to provide first insights into the potential cost-effectiveness of RNA-based therapies for SCA1 in the Netherlands.
Methods
We simulated disease progression of individuals with SCA1 using a patient-level state-transition model. Five hypothetical treatment strategies with different start and endpoints and level of effectiveness (5–50% reduction in disease progression) were evaluated. Consequences of each strategy were measured in terms of quality-adjusted life years (QALYs), survival, healthcare costs, and maximum costs to be cost effective.
Results
Most QALYs (6.68) are gained when therapy starts during the pre-ataxic stage and continues during the entire disease course. Incremental costs are lowest (− €14,048) if therapy is stopped when the severe ataxia stage is reached. The maximum costs per year to be cost-effective are €19,630 in the “stop after moderate ataxia stage” strategy at 50% effectiveness.
Discussion
Our model indicates that the maximum price for a hypothetical therapy to be cost-effective is considerably lower than currently available RNA-based therapies. Most value for money can be gained by slowing progression in the early and moderate stages of SCA1 and by stopping therapy upon entering the severe ataxia stage. To allow for such a strategy, it is crucial to identify individuals in early stages of disease, preferably just before symptom onset.
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