Abstract
Little formal research has been conducted on strategies to structure basic, preclinical, and clinical research to increase the likelihood of discovering efficacious interventions for patients with neurological diseases. How academic research is organized and funded by government agencies and foundations seems likely to affect the quality and rate of production of valued therapeutic agents. Few models for translational biomedical research, however, have been defined and no strategies have been compared. Given the narrow width of expertise and laboratory capacity of individual investigators, the complexity of identifying and manipulating mechanisms of disease components over time, and the demand for solutions from society, our continued reliance on funding therapeutic discovery through standalone investigators and projects seems counterproductive. Models are described for funding collaborations of basic and clinical scientists to work in iterative, adaptable, cross-disciplinary interactions around key progress-limiting questions. Problem-oriented collaborations require leadership, incentives, trust, ongoing assessment, and an efficient infrastructure that overcomes barriers. These models are as testable as the hypotheses that drive scientific research.