The dilemma between milestones of progression versus clinical scales in Parkinson’s disease.

Abstract:

There are significant challenges in accurately documenting the progression of Parkinson's disease (PD). The disease course is highly heterogeneous, there are no validated biomarkers, and we are reliant on repeated clinical measures to assess disease state over time. Yet, the ability to chart disease progression accurately is vital in both observational and interventional study designs, where reliable measures are critical to determine whether an outcome has been met. In this chapter, we first discuss the natural history of PD, including the spectrum of clinical presentation and expected developments through the course of the disease. We then explore in detail the current strategies for measuring disease progression, which can be broadly divided into: (i) the use of quantitative clinical scales; and (ii) determination of the onset time of key milestones. We discuss the strengths and limitations of these approaches for use in clinical trials, with a particular focus on disease modification trials. The selection of outcome measures for a particular study will depend on multiple factors, but trial duration is an important determinant. Milestones are reached over a course of years rather than months, and hence clinical scales with sensitivity to change are needed for short-term studies. However, milestones represent important markers of disease stage which are not confounded by symptomatic therapies and are of critical relevance to the patient. Prolonged but low intensity follow-up beyond a limited period of treatment with a putative disease-modifying agent may allow milestones to be incorporated into evaluation of efficacy in a practical and cost-effective way.