Statistical modeling to document disease progression

All About Parkinson's Disease

All About Parkinson's Disease By Lianna Marie

Get Instant Access

The Unified Parkinson's Disease Rating Scale is the most widely utilized tool for rating PD impairment and disability (Fahn et al., 1987). It has gained world-wide acceptance and is the primary end-point measure for most PD-related clinical trials. Its clinimetric profile has been established over two decades since its development, and reliability/validity testing has corroborated its value (Goetz et al., 2003). The scale consists of four sub-scales with scores that can be summed for a Total

UPDRS score , or each part can be analyzed separately (Part I: Cognition, Mood and Behavior; Part II: Activities of Daily Living; Part III: Motor Examination; and Part IV: Complications of Disease and Therapies). Its major application has focused on motor aspects of PD, highlighted primarily by Parts II and III with less emphasis placed on the non-motor elements captured in Part I and, to some extent, Part IV. Analyses of clinical trials examining early PD patients without symptomatic treatment demonstrate an annual increase of approximately 10 points on the Total UPDRS score (Kieburtz, 2003). The scale is highly responsive to levodopa and dopamine agonists with reductions in UPDRS scores estimated usually between 40-50% six months after introduction of therapy. The fact that symptomatic treatment dramatically improves UPDRS scores and patient function, however, has confounded the analysis of underlying disease progression once treatment is initiated. To address this issue and develop reasonable sample size calculations for measuring disease progression in the face of symptomatic treatments, longitudinal clinical trials have been re-analyzed for calculating UPDRS progression rates in this context. As part of the large NET-PD Statistical Core effort, Guimaraes et al. examined UPDRS scores from three patient series over 2-3 years under treatment with either levodopa or agonists, often supplemented with levo-dopa (Guimaraes et al., 2005). Following an initial improvement in UPDRS scores, continued dopaminergic therapy was associated with clinical decline and an annual linear 3-point progression of total UPDRS scores. This model predicts a return to pre-treatment UPDRS scores by five years. Such calculations define a base rate of progression in the context of best medical care. Subjects already treated with symptomatic therapies have traditionally been excluded from neuroprotection clinical trials because of concerns that symptomatic care confounds the interpretation of data. The 3-point annual progression in UPDRS scores across different studies and across different dopaminergic therapies is strong evidence that neuroprotective programs aimed at slowing disability/impairment progression rates can include subjects already on symptomatic care.

Was this article helpful?

0 0
All About Alzheimers

All About Alzheimers

The comprehensive new ebook All About Alzheimers puts everything into perspective. Youll gain insight and awareness into the disease. Learn how to maintain the patients emotional health. Discover tactics you can use to deal with constant life changes. Find out how counselors can help, and when they should intervene. Learn safety precautions that can protect you, your family and your loved one. All About Alzheimers will truly empower you.

Get My Free Ebook

Post a comment