Endpoints and Analyses to Discern Disease-Modifying Drug Effects in Early Parkinson’s Disease
Parkinson’s disease is an age-related degenerative disorder of the central nervous system that often impairs the sufferer’s motor skills and speech, as well as other functions. Symptoms can include tremor, stiffness, slowness of movement, and impaired balance. An estimated four million people worldwide suffer from the disease, which usually affects people over the age of 60. Presently, there is no precedent for approving any drug as having a modifying effect (i.e., slowing or delaying) for disease progression of Parkinson’s disease. Clinical trial designs such as delayed start and withdrawal are being proposed to discern symptomatic and protective effects. The current work focused on understanding the features of delayed start design using prior knowledge from published and data submitted to US Food and Drug Administration (US FDA) as part of drug approval or protocol evaluation. Clinical trial simulations were conducted to evaluate the false-positive rate, power under a new statistical analysis methodology, and various scenarios leading to patient discontinuations from clinical trials. The outcome of this work is part of the ongoing discussion between the US FDA and the pharmaceutical industry on the standards required for demonstrating disease-modifying effect using delayed start design.
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- Endpoints and Analyses to Discern Disease-Modifying Drug Effects in Early Parkinson’s Disease
The AAPS Journal
Volume 11, Issue 3 , pp 456-464
- Cover Date
- Online ISSN
- Springer US
- Additional Links
- delayed start
- disease modification
- Parkinson’s disease
- randomized start
- Industry Sectors
- Author Affiliations
- 1. Pharmacometrics, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Avenue, Building 51, Rm. 3186, Silver Spring, Maryland, 20993-0002, USA
- 2. Division of Biometrics-I, Office of Biostatistics, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA
- 3. Office of New Drugs, Division of Neurology Drug Products, Center for Drug and Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA