Body position classification using wearable sensors in infants with cerebral palsy.

Parkinson's is one of the fastest-growing neurological diseases and the third leading cause of neurological disease burden in the global ageing population. The development of disease-modifying therapies (DMTs) that can slow or halt functional decline and delay loss of quality of life and independence in the early stages of disease, by treating the underlying pathobiology of Parkinson's, is a key unmet need. With numerous promising DMT candidates under investigation to treat people with early-stage Parkinson's, there is a need for a sensitive and meaningful clinical outcome assessment (COA) to serve as a primary efficacy outcome measure in this target population. As reflected in regulatory guidance, this COA not only needs to be responsive to changes indicative of disease progression, but must also reflect how patients feel or function in day-to-day life (e.g., ability to perform relevant tasks or functions impacted by the disease) to ascertain the unequivocal clinical benefit of the therapeutic intervention. The Movement Disorder Society – Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the current gold standard in clinical practice for measuring Parkinson's severity, including motor features rated by clinicians (part III), and motor (part II) and non-motor (part I) features reported by patients. Originally developed without consideration of disease stage, the MDS-UPDRS was mostly developed and validated in patients with moderate- to late-stage Parkinson's. With the shift towards DMT intervention earlier in the disease continuum, bespoke analyses evaluating the ability of MDS-UPDRS parts II and III to assess the earliest features of Parkinson's have demonstrated psychometric limitations (e.g., floor effects, suboptimal scale-to-sample targeting, disordered thresholds for some items). In the context of selecting a primary clinical efficacy endpoint for DMT pivotal trials, these findings suggest that some MDS-UPDRS items may not be sufficiently sensitive to detect disease progression in early-stage Parkinson's.