Realizing that 60% to 80% of dopa- minergic nigrostriatal neurons are nonfunctional at the time of clinical diagnosis, there is an emerging consen- sus that disease-modifying treatments should be initi- ated in the earliest stages of Parkinson's disease (PD). To date, clinical trial designs and metrics in PD have been focused on motor symptoms as the core feature of the clinical disease. To identify earlier or ''pre-motor'' populations in PD, new markers have been proposed. We address the prerequisites needed to use these pre-motor markers in clinical trials for the selection of subjects, definition of populations, and monitoring of dis- ease progression. This may require the development of new diagnostic criteria potentially based on non-motor clinical signs, imaging techniques, or biological features, all requiring discussion in a regulatory framework. Ques- tions addressed include: Which steps must be taken to gain a broad consensus in the field from academic opin- ion leaders, patient advocacy groups, regulatory bodies, and industry? How do we prevent the selection of sub- groups, which may not be representative of the full dis- ease spectrum? Is there a way forward in personalized medicine? How do we balance risk and benefit in an at- risk population? While many tools are available, a con- certed effort is required to develop integrated data sets, as well as to achieve the necessary standardization for multicenter clinical trials. To this end, public-private con- sortia (including academic centers, patient advocacy groups, and industry) will be of crucial importance to prospectively investigate and define the best tools and treatment paradigms. V C 2012 Movement Disorder Society
