Failed trials for central nervous system disorders do not necessarily invalidate preclinical models and drug targets
Anton Bespalov, Thomas Steckler, Bruce M. Altevogt, Elena Koustova, Phil Skolnick, Daniel R. Deaver, Mark John Millan, Jesper F. Bastlund, Darı́o Doller, Jeffrey M. Witkin, Paul C. Moser, Patricio O’Donnell, Ulrich Ebert, Mark A. Geyer, Eric P. M. Prinssen, Theresa M. Ballard, Malcolm Robert Macleod · Nature Reviews Drug Discovery · 2016
A recent article identified five key technical determinants that make substantial contributions to the outcome of drug R&D projects (Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework. Nat. Rev. Drug Discov . 13 , 419–431 (2014)) 1 . Careful consideration of such determinants might be particularly valuable in the fields of neurology and psychiatry, in which successful drug development has declined precipitously over the past decade. This decline has largely been fuelled by a high failure rate in the translation of preclinical efficacy findings, caused by multiple factors (see Supplementary information S1 (table) ), including limited training and poor protocol design, inadequate animal models, insufficiently validated therapeutic targets and problems with data handling and reporting.