THE NEED FOR LEVODOPA AS AN END-POINT OF PARKINSONS-DISEASE PROGRESSION IN A CLINICAL-TRIAL OF SELEGILINE AND ALPHA-TOCOPHEROL

Progression of Parkinson's disease (PD) can be detected through change s in clinical ratings or disability assessments. A clinical trial, Dep renyl and Alpha-Tocopherol Antioxidative Therapy of Parkinsonism (DATA TOP), used a novel study end point: increase in parkinsonian disabilit y to the extent that investigators determined the need for treatment w ith levodopa. We analyzed DATATOP results to learn if this operational ly-defined end point could be reproduced from elements of the Unified PD Rating Scale (UPDRS) and other conventional clinical scales. Our an alysis involved UPDRS, Schwab and England Activities of Daily Living ( S-E ADL), and Hoehn and Yahr (H-Y) scores when DATATOP subjects reache d the study end point. Various UPDRS components were examined, includi ng subscores measuring severity of impaired ADL, bradykinesia, postura l instability and gait difficulty, tremor, and rigidity. Data from sub jects reaching the end point were com pared with assessments of those DATATOP subjects who did not, matched for the same duration of enrollm ent. All measures showed subjects who reached the end point had signif icantly greater mean impairment than did controls, although the two gr oups had substantial overlap. Multivariate analysis by using condition al logistic regression suggested that the end point was determined mor e by functional (S-E ADL and the UPDRS ADL scores) than by clinical ex amination criteria. The method of classification and regression trees suggested a simple decision tree splitting, respectively, on S-E ADL, UPDRS ADL, H-Y score, and UPDRS ADL again, with an estimated overall m isclassification probability of 18%. We conclude that the DATATOP end point cannot be fully reproduced from the traditional clinical measure s, although it can give results that are consistent with these scales in a well-designed clinical trial.