title: Minimal clinically important difference in Parkinson's disease as assessed in pivotal trials of pramipexole extended release.
abstract: Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson's Disease Rating Scale (UPDRS) scores in early Parkinson's disease (EPD) and for UPDRS scores and "OFF" time in advanced Parkinson's disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves "a little better" on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR) for UPDRS II were -1.8 and -2.0, for UPDRS III -6.2 and -6.1, and for UPDRS II + III -8.0 and -8.1. MCIDs in APD for UPDRS II were -1.8 and -2.3, for UPDRS III -5.2 and -6.5, and for UPDRS II + III -7.1 and -8.8. MCID for "OFF" time (pramipexole ER, pramipexole IR) was -1.0 and -1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.
authors.affiliation: University of South Florida, Parkinson's Disease and Movement Disorders Center, Byrd Institute, National Parkinson Foundation Center of Excellence, Tampa, FL 33613, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hauser
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT 06877, USA.
authors.forename: Mark Forrest
authors.initials: MF
authors.lastname: Gordon
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Werner
authors.identifier: 0000-0003-4367-0971
authors.initials: W
authors.lastname: Poewe
authors.affiliation: Center for Neurodegenerative Diseases, Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Barone
authors.affiliation: Department of Clinical Neurosciences, University College London Institute of Neurology, London, UK.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Schapira
authors.affiliation: Clinical Investigation Center, INSERM CIC-9302 and UMR-825 and Departments of Clinical Pharmacology and Neurosciences, Toulouse University Hospital, Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rascol
authors.affiliation: Boehringer Ingelheim France S.A.S., Reims, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Debieuvre
authors.affiliation: Boehringer Ingelheim Pharmaceuticals, GmbH & Co. KG, Ingelheim, Germany.
authors.forename: Mandy
authors.initials: M
authors.lastname: Fräßdorf