Objective/Rationale:
In clinical trials, the progression of Parkinson’s disease (PD) is primarily measured by the change in total Unified Parkinson Disease Rating Scale (UPDRS) score between baseline visit and a final study endpoint. Progression of UPDRS, however, is not the same for all PD patients and varies with time. The primary objective here is to re-initiate the development of a mathematical model describing the progression of PD by using previously modeled and non-modeled clinical trial datasets.
Project Description:
There have been previous efforts to model and quantify the full longitudinal progression of PD symptoms using data from several different clinical trials. These models have been used to describe the patterns of UPDRS changes over time and quantify drug actions in order to enhance the design of PD clinical trials. However, since these modeling efforts have concluded, new data sets have become available. Through this project, data from selected studies of PD therapeutic trials involving subjects in the early stages of disease will be organized in a standard format for general modeling purposes. These data will be used to evaluate the previous PD models by assessing how UPDRS progression parameters change when new data are incorporated. The updated models will also be used to characterize the pattern of progression, and estimate its variability and identify its sources.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Designing and executing a clinical trial to test potential disease modifying therapeutic agents for PD is complicated and costly. A ‘model-based drug development’ approach can improve clinical trial efficiency by providing a better understanding of drug effects on disease progression and by planning various design aspects of a trial through simulation. The current analyses will benefit the PD research community by updating previous disease models and quantifying disease progression and its variability.
Anticipated Outcome:
At the completion of this project, it is expected that an updated model describing UPDRS changes over time will provide more precise estimates of progression parameters ultimately leading to a more informative and improved PD progression model. This model may serve as a platform for its own updating and refining as additional clinical trial data becomes available.
Final Outcome
Disease progression models characterize changes in individuals’ disease severity over time. In Parkinson’s disease (PD), several models have described changes in the Unified Parkinson’s Disease Rating Scale (UPDRS), the traditional measurement of disease severity in PD drug trials. We evaluated and updated a previous model of PD Progression using newer data collected from several clinical trials. The updated PD progression model was able to estimate and compare individual PD progression, which provided the opportunity to explore factors that might explain why some people progress differently than others.