Natural History of Disorders Screenable in the Newborn Period (R01 Clinical Trial Optional)

The NIH's "Natural History of Disorders Screenable in the Newborn Period" (PAR-25-227) funding opportunity supports research to enhance understanding of the natural history of disorders identified through newborn screening or likely to benefit from future screening. This opportunity, reissued by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), aims to facilitate studies that characterize symptom progression, improve diagnosis, and inform intervention strategies for early-identified conditions. This knowledge is essential for refining clinical approaches, supporting families, and developing treatments that target specific stages of disease progression. Additionally, genotype-phenotype correlation studies and analyses of genetic or environmental factors can provide insights into clinical variability and improve individualized care strategies. Key goals include establishing comprehensive data on the development of disorders over time, identifying biological mechanisms, understanding genetic and clinical diversity, improving diagnostic precision, and enabling longitudinal studies to inform intervention timing and efficacy. Applicants may focus on a range of heritable disorders, such as metabolic and genetic syndromes, neuromuscular diseases, or immunodeficiencies. Multi-state research consortia are encouraged, and studies may include registries or data systems to track patient outcomes longitudinally. Eligible applicants include institutions of higher education, nonprofits, for-profit organizations, local and federal government entities, and foreign entities. The NIH anticipates making multiple awards, depending on appropriations and proposal quality, with budgets aligned with project needs and project periods extending up to five years. Applications can include clinical trials, but proposals should prioritize non-interventional, natural history study designs that address the specific aims of the NOFO. Applications must demonstrate how their research will improve clinical decision-making, particularly for conditions that vary in age of onset. Proposals should outline the research landscape, detail the rationale for the study, and explain the utility of natural history data in enhancing care. Projects focusing on innovative data collection methods, biomarkers, or techniques for addressing underserved populations are particularly encouraged. The research plan should incorporate standardized data collection strategies, potentially using NIH Common Data Elements, to enhance data integration and facilitate future collaborative research. Review criteria emphasize the significance, scientific rigor, and feasibility of the proposed studies. Reviewers will consider the innovation of study design, data collection systems, and the expertise of the investigative team. Proposals must include strategies to ensure adequate diversity in study populations and plans for managing data sharing per NIH's Data Management and Sharing Policy. Letters of intent are requested 30 days before submission, and deadlines follow NIH's standard cycles, with the earliest submission date being January 5, 2025. Applications exceeding $500,000 in direct costs per year require consultation with NIH program staff six weeks before submission.