ABSTRACT The goal of this U24 application is to establish the Data Integration, Algorithm Development and Operations Management Center (DAC) for NIAMS' Back Pain Consortium (BACPAC) Research Program to ensure that the research objectives are met. The objectives of BACPAC include (i) discovery of lower back pain mechanisms through expert application of clinical and translational medicine methodologies; (ii) identification of new interventions targeted to individual patients through knowledge of established and newly discovered mechanisms; and (iii) evaluation of promising interventions to determine those that warrant further study, potentially leading to regulatory approval. A successful BACPAC research program will be based on cutting edge technologies and reflect the patient-centric focus that is critical to any investigation in this chronic and burdensome disease. Central to this success will be an innovative, forward-looking, and productive DAC that brings cohesion to research performed by the participating Mechanistic Research Centers, Technology Research Sites, and Phase 2 Clinical Trials Centers. DAC Investigators will share their vision and provide scientific leadership and organizational support to the BACPAC Consortium. Our research plan consists of designing and conducting clinical trials with precision interventions in stratified patient populations. Precision medicine interventions that focus on identifying the best treatments for individual patients, instead of the best treatments for the most patients, could improve overall outcomes among this heterogenous patient population. Key elements of the DAC that will enhance collaboration and research progress include experienced leadership, innovative design and analysis methodologies (e.g., sequential adaptive designs, machine learning, neural networks, Q-learning), comprehensive research operations support, a state-of-the-art data management and integration system, and superior administrative support. Our communications infrastructure will provide both public and private websites and a social media presence to effectively disseminate appropriate information to BACPAC investigators, participants, and the public. We will develop a secure, user- friendly advanced data management and integration system that includes web-based access for surveys, data entry, research management (including comprehensive reporting, biosample tracking and performance-based reimbursement tools), integration with external applications, and quality control. Our research operations and administration teams will provide a solid foundation to the BACPAC Research Program by facilitating meetings, collaborative document preparation, tracking of regulatory compliance, and support for abstract and publication preparation across the BACPAC Consortium. Together, this integrated structure will set the stage for technology assessments, solicitation of patient input and utilities, and the evaluation of high-impact interventions through the innovative design and sound execution of clinical trials, leading to effective personalized treatment approaches for patients with chronic lower back pain.

PROJECT NARRATIVE Chronic low back pain (cLBP) affects over 10% of adults in the US, contributing to the burden of disability and health care costs, and putting those suffering from cLBP at risk of opioid addiction or even overdose. The National Institutes of Health is funding a patient-centric research program to discover new low back pain mechanisms and develop improved diagnostic and treatment algorithms through extensive patient phenotyping and use of precision medicine approaches. Our proposal is to provide network leadership and operations support, state-of-the-art data integration and analytics infrastructure, and bioinformatics and statistical expertise to support the research goals of the BACPAC.