‘Mind the gap‘ between clinician-based and patient-relevant outcome measures.

Radboudumc researchers, Roderick Maas and Bart van de Warrenburg, theme Disorders of movement, evaluated health-related quality of life, depressive symptoms, fatigue, and physical activity in mildly to moderately affected patients with SCA3, which is the most common inherited spinocerebellar ataxia (SCA) type worldwide. Specifically, they aimed to examine the relationships between patient-reported outcome measures (PROMs) and objective, clinician-based disease severity measures. The results of this study, which was conducted at the Radboudumc Expert Center for Rare and Genetic Movement Disorders, have been published in The Cerebellum on 10 March 2021.

There are exciting therapeutic developments for a number of rare genetic movement disorders, including the dominantly SCAs. Urgent work is needed to reach actual trial-readiness for these disorders. One of the principal dilemmas involves the choice of relevant endpoints that capture meaningful changes in gradually progressive conditions. Commonly used outcome measures include ratings of disease severity by physicians, but these will likely not reflect the actual difficulties patients are facing in daily life. There is currently an increasing interest in PROMs which provide valuable insights into self-perceived health status. PROMs need to be carefully studied, in particular in the early disease stages.

SCA3 patients reported lower quality of life, more depressive symptoms, and higher levels of fatigue than healthy controls. The amount of physical activity did not differ between both groups. Quality of life was primarily determined by fatigue and not by ataxia severity. Depressive symptoms were related to disease duration and fatigue but not to markers of motor disease progression.

Taken together, in early-stage SCA3 patients, decreased quality of life, increased levels of fatigue, and a higher number of depressive symptoms do not merely reflect motor impairment as captured by the commonly used rating scales. The observed discordance between patient-reported and clinician-based outcomes indicates that these measures genuinely evaluate distinct aspects of disease and emphasizes their complementariness in therapeutic trials.

Publication

Maas RPPWM, Schutter DJLG, van de Warrenburg BPC. Discordance Between Patient-Reported Outcomes and Physician-Rated Motor Symptom Severity in Early-to-Middle-Stage Spinocerebellar Ataxia Type 3. Cerebellum. 2021 Mar 10. doi: 10.1007/s12311-021-01252-9.