The AAPS Journal

, 11:456

Endpoints and Analyses to Discern Disease-Modifying Drug Effects in Early Parkinson’s Disease

  • Venkatesh Atul Bhattaram
  • Ohidul Siddiqui
  • Leonard P. Kapcala
  • Jogarao V. S. Gobburu
Research Article

DOI: 10.1208/s12248-009-9123-2

Cite this article as:
Bhattaram, V.A., Siddiqui, O., Kapcala, L.P. et al. AAPS J (2009) 11: 456. doi:10.1208/s12248-009-9123-2

Abstract

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.

Key words

delayed startdisease modificationneuroprotectionParkinson’s diseaserandomized start

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Venkatesh Atul Bhattaram
    • 1
  • Ohidul Siddiqui
    • 2
  • Leonard P. Kapcala
    • 3
  • Jogarao V. S. Gobburu
    • 1
  1. 1.Pharmacometrics, Office of Clinical Pharmacology, Center for Drug Evaluation and ResearchUS Food and Drug AdministrationSilver SpringUSA
  2. 2.Division of Biometrics-I, Office of Biostatistics, Center for Drug Evaluation and ResearchUS Food and Drug AdministrationSilver SpringUSA
  3. 3.Office of New Drugs, Division of Neurology Drug Products, Center for Drug and Evaluation and ResearchUS Food and Drug AdministrationSilver SpringUSA