Novel Assays to Address Translational Gaps in Treatment Development (UG3/UH3 Clinical Trial Optional)

The National Institute of Mental Health (NIMH) invites applications for the phased cooperative agreement funding opportunity, "Novel Assays to Address Translational Gaps in Treatment Development." This initiative seeks to optimize and evaluate neurophysiological measures as pharmacodynamic (PD) assays in both healthy humans and relevant preclinical species. It aims to enhance translational science by identifying measures that reliably reflect neurophysiological processes disrupted in mental disorders and can be used in therapeutic development pipelines. The research will focus on in vivo measures that demonstrate coherence between preclinical species and humans, improving the predictive value of preclinical findings and identifying inconsistencies that limit speculative extrapolations. This opportunity consists of two phases: the UG3 phase for preparatory testing and prioritization and the UH3 phase for measure evaluation. The UG3 phase supports the optimization of translational assays in both species, including studies needed to align measures and pharmacologic manipulations. The UH3 phase evaluates optimized measures for reliability and coherence across species using dose-ranging pharmacokinetic/pharmacodynamic (PK/PD) studies. Applications must include detailed plans for both phases, including specific aims, experimental designs, and milestones. Both positive and negative results will provide valuable insights into the translational applicability of preclinical assays. Eligible measures include quantitative neurophysiological and behavioral assays targeting processes like vigilance, neural plasticity, reward processing, and cognitive or affective regulation. Examples include EEG or MEG spectral analyses, measures of sleep microstructure, and tasks assessing impulsivity or cognitive effort. Priority will be given to assays that integrate behavioral paradigms with physiological measures or novel techniques derived from cutting-edge tools like optogenetics. Mechanistic studies of brain systems or clinical testing of new therapeutics fall outside the scope of this initiative. Applications may be submitted by U.S. and non-U.S. entities, including higher education institutions, nonprofits, for-profit organizations, and other eligible groups. Budgets are not capped but must reflect project needs, with the UG3 phase lasting one to three years and the UH3 phase not exceeding three years. NIH will support travel costs for annual meetings to foster collaboration among funded investigators and ensure alignment with program goals. Key dates include the first application deadline on February 21, 2025, with subsequent deadlines on June 20, 2025. Letters of intent are recommended 30 days before the application deadline. Projects will be evaluated on their significance, innovation, rigor, feasibility, and relevance to the therapeutic development pipeline. Investigators must include detailed plans for data sharing, resource dissemination, and participant protection, ensuring transparency and reproducibility. Successful projects will significantly advance translational research by validating tools that bridge the gap between preclinical and clinical studies.