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Scientific discovery and clinical investigation are critical for developing and evaluating new treatments and can have substantial public health benefits. A detailed analysis of clinical trials funded by the National Institute of Neurological Disorders and Stroke found that the public return on investment in clinical trials has been substantial. In addition to the inherent risks involved in clinical trials, the challenges of translating scientific advances into new therapeutic advances are increasing. Many of the challenges of drug development are particularly acute for treatments of neurological conditions. The scope of clinical trials for neurological conditions is rapidly expanding to address orphan indications, biologics, medical devices, surgeries, and comparative effectiveness studies. In addition to drugs, clinical trials frequently evaluate devices for neurological conditions. High quality data on surgical interventions, such as temporal lobe resections for epilepsy are critical to understanding their relative risks and benefits in the target populations.