Food allergy (FA) affects up to 8% of young children and 3-6% of the entire U.S. population, and its prevalenceappears to have increased significantly over the past 15 to 20 years. The Consortium for Food Allergy Research(CoFAR) is a network of research sites tasked with advancing FA prevention and treatment through consortium-wide clinical trials. The next version of CoFAR will establish a national network of 6-7 Clinical Research Units(CRUs), with proven FA trial expertise, infrastructure and access to allergy populations. The CRUs, under thedirection of the CoFAR Leadership Center, will participate in collaborative multicenter trials of new FA therapies.The University of North Carolina Food Allergy Initiative (UNCFAI), a leader in FA clinical research, proposes toestablish a CRU, leveraging the expertise and experience of the PI, Dr Wesley Burks, a world class FA researchinfrastructure at UNC, and an innovative recruitment strategy covering a large and diverse regional FA patientpopulation. The specific aims are: Aim 1: Expand UNCFAI by the development of a dynamic, collaborative andsustainable CoFAR Clinical Research Unit to rapidly implement clinical trials in collaboration with the entireconsortium. Aim 2: Promote career development of young clinician-investigators in food allergy research Aim 3:Foster participation of researchers, physicians, patients and patient support groups in CoFAR clinical trials Aim4: Conduct an innovative clinical trial using a SMART framework. The UNC CRU has several assets that willbenefit CoFAR endeavors, including a state-of-the-art Clinical and Translational Research Center, a highcapacity Manufacturing Facility and advanced study design and biostatistics expertise. The UNC Divisions andAllergy and Immunology will recruit and train junior investigators interested in FA research, drawing on divisional,departmental and university-wide training programs. The CRU will draw on (i) local and regional health carenetworks, private allergy practices and patient support groups, (ii) large health care databases, like the CarolinaData Warehouse for Health, and (iii) NC TRaCS community outreach strategies, to inform the broad FApopulation of North Carolina about CRU activities and to recruit these patients into CoFAR trials. As part of theapplication the UNC CRU proposes a multicenter trial to investigate the relative efficacy of specific combinationsand sequences of high-, medium- and low-dose immunotherapies (oral, sublingual and epidermal, respectively)to establish and maintain peanut insensitivity with minimal allergic side effects and maximal compliance. Thestudy uses a sequential, multiple assignment, randomized (SMART) trial design, which is a significant advanceon traditional multi-arm and crossover studies, in that it allows simultaneous testing of multiple treatmentmodalities, combinations and sequences, while accounting for additive effects. The treatment and biomarkerdata generated from this trial will inform a larger comprehensive future study. The use of tailoring variables inthe trial design will allow us to explore the optimal individualized strategy for the treatment of peanut allergy.