Research Article

The AAPS Journal

, Volume 11, Issue 3, pp 456-464

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

  • Venkatesh Atul BhattaramAffiliated withPharmacometrics, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration
  • , Ohidul SiddiquiAffiliated withDivision of Biometrics-I, Office of Biostatistics, Center for Drug Evaluation and Research, US Food and Drug Administration
  • , Leonard P. KapcalaAffiliated withOffice of New Drugs, Division of Neurology Drug Products, Center for Drug and Evaluation and Research, US Food and Drug Administration
  • , Jogarao V. S. GobburuAffiliated withPharmacometrics, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration Email author 

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 start disease modification neuroprotection Parkinson’s disease randomized start