title: Challenges in detecting disease modification in Parkinson's disease clinical trials.
abstract: Despite the wealth of encouraging data from numerous compounds that demonstrate "neuroprotection" in pre-clinical studies of Parkinson's disease, and despite numerous clinical trials, to date, no intervention has been demonstrated to able to modify the course of disease progression. While this "failure to translate" is likely due to numerous factors including our incomplete understanding of the pathogenic mechanisms underlying PD together with excessive reliance on data from the toxin-based animal models of PD, here we will discuss the "structural issues" pertaining to inadequate clinical trial design, selection of inappropriate endpoints and poor patient selection which are often not addressed following failed disease modification trials. Future directions to overcome these challenges such as reducing the heterogeneity of patient cohorts, identifying and utilising a pre-diagnostic population, embracing a personalised medicine approach and utilising novel trial designs may be required to ultimately fulfil the goal of conclusively demonstrating evidence of disease modification.
authors: Sobell Department of Motor Neuroscience, UCL Institute of Neurology & The National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United Kingdom. Electronic address: d.athauda@ucl.ac.uk.
authors: Dilan
authors: D
authors: Athauda
authors: Sobell Department of Motor Neuroscience, UCL Institute of Neurology & The National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, United Kingdom. Electronic address: t.foltynie@ucl.ac.uk.
authors: Thomas
authors: T
authors: Foltynie
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000209:etiology; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis* / Q000628:therapy*
chemical_list: D018696:Neuroprotective Agents