Researchers Prof Bart van de Warrenburg, Dr Roderick Maas and Kristofoor Leeuwenberg at Radboud University Medical Center in the Netherlands have recently published a paper in the journal Cerebellum on their work as part of the SIMPATHIC research project. The SIMPATHIC project is a European project that aims to develop drug repurposing for rare neurological, neurometabolic and neuromuscular disorders by exploiting similarities in the underlying cause of the conditions. The project includes nine conditions, of which SCA3 is one.
SCA3 is a hereditary, slowly progressive condition. The main symptom of SCA3 is ataxia. In a clinical trial testing a treatment for SCA3, the symptoms need to be accurately measured over time. This is more challenging for a condition which progresses slowly like SCA3. A number of methods have been suggested for measuring ataxia symptoms over time, but all have limitations. Increasing drug development in SCA3 means that trial-readiness is more important than ever before, therefore having a robust way of measuring the effect of a treatment in a trial is vital.
In this paper, the Goal Attainment Scale (GAS) is proposed as a method which could be used to capture variability in ataxia symptoms between individuals in a patient-centred way. The tool involves setting personalised, symptom-related goals that are evaluated over the period in which a person is undergoing treatment. Use of the GAS in clinical trials has been limited so far. This research explores the feasibility of the GAS, and whether it covers all aspects of ataxia. The researchers studied this through interviews with 15 people with SCA3 at different stages of the condition (5 with mild ataxia, 5 with moderate ataxia and 5 with severe ataxia).
Participants were interviewed about their goals by a single assessor. Before the interview, participants were asked to document their symptoms and choose their top three priorities. They were then asked to create five goals. The goals were formed around a hypothetical treatment for improving SCA3 symptoms, with participants asked what they hoped to achieve after six months of treatment. If the GAS were used in a trial, after 6 months of treatment a score would be assigned to each goal for each person (with the score indicating whether the goal was achieved, or not). Scores would then be combined per participant across their goals, and the overall average would be converted into a score. The score would be compared between those that received treatment and those that did not, to evaluate how effective the treatment is.
GAS goals can be grouped in two ways: by which body functions are important in the goal, or by which parts of daily activity and participation the goal is connected to. In this study, within the body functions domain, most participants’ goals were related to balance issues (30.2%), followed by coordination of limb movements (11.1%), and visual function (11.1%). Balance-related goals were ranked most important across all stages of disease. Within the activity and participation domain, most goals were related to walking/mobility-related participation (39.7%), carrying out daily routine (12.7%), and fine hand use (7.9%). In this domain, walking/mobility-related participation-related goals were ranked most important across all stages of disease.
The researchers found that symptoms and goals varied depending on the stage of the disease. People with SCA3 initially experience mild balance issues and more non-specific symptoms such as fatigue and reduced exercise tolerance. Therefore, for study participants with mild SCA3, goals
surrounding balance included only needing to take one corrective step every 20 steps to avoid losing balance, and to sleep more than 6 hours per night on average. As mobility becomes more limiting, its impact increases and starts to dominate daily concerns. For example, for study participants with severe SCA3, goals surrounding balance included walking safely for 10 meters without a walking aid or without losing balance. In more advanced stages of the condition, when independent mobility is mostly lost and more body systems are affected, non-mobility-related symptoms become more important in people’s everyday experiences, with goals such as ‘to have part of the day without dizziness 5 to 8 times per month’, or ‘to speak clearly for 5 minutes without needing to repeat words to be well-understood’.
The study showed that the GAS is feasible in SCA3 and is it relevant to all aspects of ataxia. However, the study did not include follow-up scoring of goals. Additionally, the small sample size of 15 people limits the extent to which the results from this study can be generalised to the wider SCA3 population. Additionally, the interviews were conducted by a single assessor, when in clinical practice individuals are more likely to be assessed by multiple clinicians. Overall, if these limitations are addressed, the GAS could be a valuable tool in SCA3 and trials of other ataxias.
Read more about the SIMPATHIC project here.
