A ‘BOLD’ experiment in defining the utility of fMRI in drug development

According to the Federal Drug Agency (FDA), nine out of ten compounds fail in human studies and a z50% failure rate is found for drugs in late-stage Phase 3 clinical trials (Schachter and Ramoni, 2007); this may be worse in the case of CNS clinical phase development. Complex factors including scientific, business, regulatory and intellectual property issues (see US Government Accountability Office, Report to Congress, Nov 2006, http://www.gao.gov/new.items/d0749.pdf) may contribute to this high failure rate. In addition, drug registrations are the focus of political scrutiny (Kola and Landis, 2004). These pressures are contributing to the diminished pipelines for new drugs at large pharmaceutical companies (Cuatrecasas, 2006; Federsel, 2006). New approaches are needed to improve the success rates of CNS compounds selected for clinical trials that include an ability to predict dose, identify surrogate markers and assess tolerability. Interrogation of neural systems using a ‘systems biology’ approach (i.e., neural basis for behavioral changes), may offer solutions to help accelerate the drug discovery and development process, improve the success rate, and ultimately reduce costs. In recent years, the pharmaceutical industry has become very interested in the potential application of functional magnetic resonance imaging in drug development. While the