Objective: To quantify the progression of Parkinson disease (PD) in patients receiving inactive control treatments in three Parkinson’s disease clinical trials.
Methods: Data from 1027 patients receiving pharmacologically inactive control treatments were obtained from 3 clinical trials (DATATOP, ELLDOPA,TEMPO (1-3)) and merged using SAS (9.1). Progression was modeled using a combination of a linear function and a Bateman function (4) with mixed effects non-linear regression. A mixture model was used to distinguish patients who improved and then relapsed (placebo responders) from those who worsened and then improved (nocebo responders). Efforts were made to find demographic covariates (sex, age, weight, fat free mass, BSA, menopausal status) which might predict progression or treatment response. The time for each patient to terminate from the trial was described by a constant baseline hazard with an exponential function of disease status score (UPDRS). Model selection was determined by evaluation of bootstrap confidence intervals of parameters and by visual predictive check.
Results: Population average baseline disease status,S0, is 23.1 UPDRS units and the disease worsen at 12.7 UPDRS units per year. The peak placebo response was -5.1 UPDRS units in 84% of patients while the peak nocebo response was 9.2 units in 16% of patients. The absorption half life was 204 days and the elimination half life was 0.81% longer than absorption. Age was associated with a 0.51% increase per year in baseline status. There were no effects of other covariates. The variability of the peak placebo/nocebo response in ELLDOPA and TEMPO was about 25% of that estimated in DATATOP. There were no other differences in the progress model parameters between the clinical trial populations. The baseline hazard for termination from TEMPO was 20 times greater than for DATATOP while the influence of increasing UPDRS on termination was similar for all 3 trials.
Conclusions: The time course of UPDRS response in clinical trials of Parkinson’s disease is very similar despite different designs and periods of follow up.
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