Levodopa slows progression of Parkinson's disease. External validation by clinical trial simulation

被引:48
作者
Chan, Phylinda L. S.
Nutt, John G.
Holford, Nicholas H. G.
机构
[1] Univ Auckland, Dept Pharmacol & Clin Pharmacol, Fac Med & Hlth Sci, Auckland 1, New Zealand
[2] Portland VA Med Ctr, Dept Neurol & Physiol & Pharmacol, Portland, OR USA
[3] Oregon Hlth & Sci Univ, Portland, OR 97201 USA
关键词
clinical trial simulation; DATATOP; disease progress model; ELLDOPA; Parkinson's disease; protective treatment;
D O I
10.1007/s11095-006-9202-3
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
To externally validate the model predictions of a DATATOP cohort analysis through application of clinical trial simulation with the study design of the ELLDOPA trial. The stochastic pharmacokinetic-pharmacodynamic and disease progress model was developed from the large DATATOP cohort of patients followed for 8 years. ELLDOPA was designed to detect a difference between placebo and levodopa treated arms in the total Unified Parkinson's Disease Rating Scale (UPDRS) taken at baseline and following 2 weeks levodopa washout after 40 weeks of treatment. The total UPDRS response was simulated with different assumptions on levodopa effect (symptomatic with/without disease modifying capability) and washout speed of symptomatic effect. The observed results of ELLDOPA were similar to the model predictions assuming levodopa slows disease progression and has a slow washout of symptomatic effect. This simulation work confirmed the conclusion of the DATATOP analysis finding that levodopa slows disease progression. The simulation results also showed that a dose-related increased rate of progression in Parkinson's disease, obscured by symptomatic benefit, is very unlikely. Finally, the simulation results also shown that 2 weeks washout period was not adequate to completely eliminate the symptomatic benefits of levodopa.
引用
收藏
页码:791 / 802
页数:12
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