PROJECT SUMMARY/ABSTRACT Bronchopulmonary dysplasia (BPD), a form of chronic lung disease following premature birth, affects more than 10,000 U.S. infants annually and leads to death, long-term respiratory dysfunction, growth failure and neurodevelopmental impairment, as well as substantial healthcare costs. Despite enormous efforts devoted to researching the prevention of BPD, there has been little improvement in BPD incidence during the last decade, with greater than one-third of very low birth weight infants affected. Vitamin A therapy is among the few therapies proven in large randomized clinical trials to reduce the incidence of BPD; the most recent Cochrane review of trials of vitamin A therapy (2016) showed that a meta-analysis of 10 trials supported its efficacy. However, clinical uptake of this therapy has been variable. Recent studies estimate that less than one-quarter of trial-eligible infants in the U.S. receive vitamin A therapy due to concerns about its cost and continued relevance two decades after the principal clinical trial, by the Eunice Kennedy Shriver NICHD Neonatal Research Network, was published. Neonatologists are faced with the daily question of whether to use vitamin A therapy yet lack evidence to support their decision-making. The proposed work will evaluate the cost- effectiveness of utilizing risk-targeted approaches to administer vitamin A therapy to infants most likely to benefit from it. We will use previously elaborated clinical trial interpretation methods based on multivariable risk prediction to evaluate for treatment effect heterogeneity in the NICHD Neonatal Research Network Vitamin A Trial, the largest clinical trial of vitamin A therapy. Using recent data from the same Network, we will evaluate how changes in the spectrum and incidence of BPD since the trial was performed affect interpretation of the trial results. We will compare the incremental costs and benefits of alternative risk-targeted applications of vitamin A therapy within the recent cohort. The overall goal of this research is to develop objective, evidence- based methods to guide optimal application of vitamin A therapy to reduce the clinical and public health burden of BPD. Methods explored in this work will also be applicable to clinical trial interpretation related to other clinical questions, with the objective to improve decision-making surrounding the clinical and public health impact of implementing clinical trial results in neonatology. Importantly, the research and training plan elaborated here, focused on collaborative interdisciplinary science and translation of methods from other fields to neonatology, will provide the applicant with a solid foundation to develop as a productive, independent clinician-scientist with skills to improve the interpretation of scientific evidence in clinical practice.