Patient-centered development of clinical outcome assessments in early Parkinson disease: key priorities and advances
Tiago Mestre, Glenn T. Stebbins, Diane Stephenson, David T. Dexter, Karen K. Lee, Yuge Xiao, Tien Dam, Catherine Kopil, Tanya Simuni
Abstract
Parkinson disease (PD) is a progressive neurodegenerative disorder with a societal burden expected to increase rapidly. In some countries, PD incidence could double in the next 50 years 1 . It is well-established that in the years preceding the emergence of parkinsonian features that currently enable a clinical diagnosis of PD 2 , various motor and non-motor manifestations such as REM sleep behavior disorder (RBD), hyposmia or constipation 3 become apparent as an expression of the underlying biology. Although dopaminergic therapy changed dramatically the natural history of the disease and improved the quality of life of those living with clinical PD, these symptomatic treatments are often associated with side effects such as motor complications, and their effectiveness can be reduced over time (or become ineffective) for some features of PD, such as gait and balance. In addition, there is a lack of effective therapies for many non-motor features of PD. There is no therapy able to slow down, halt, or reverse PD progression. In the last 12 months, the field has converged on the urgent need to develop a biological definition and staging/classification of PD to enable therapeutic intervention studies that target the relevant biological process(es), ideally before the earliest clinical signs of parkinsonism 4 , 5 . Biologically targeted therapies are expected to delay the emergence of key disease milestones such as the presence of diagnostic motor features, treatment-associated motor complications, postural instability, dysautonomia, or dementia 6 . A direct implication of being able to diagnose the underlying biology before the emergence of a diagnostic parkinsonism is the need to measure the earliest clinical changes to evaluate the impact of therapeutic interventions earlier in the disease using outcomes that are relevant to those with a lived experience. In summary, regulatory-accepted clinical outcome assessments (COAs) sensitive to clinical changes in early biological disease are urgently needed.