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

Phylinda L.S. Chan, John G. Nutt, Nicholas H.G. Holford

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Purpose. 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. Methods. 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. Results. The observed results of ELLDOPA were similar to the model predictions assuming levodopa slows disease progression and has a slow washout of symptomatic effect. Conclusions. 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.

Original languageEnglish (US)
Pages (from-to)791-802
Number of pages12
JournalPharmaceutical Research
Issue number4
StatePublished - Apr 2007


  • Clinical trial simulation
  • Disease progress model
  • Parkinson's disease
  • Protective treatment

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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