The UNC Core Center for Clinical Research
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ABSTRACT – OVERALL The overall goal of the University of North Carolina at Chapel Hill (UNC) Core Center for Clinical Research (CCCR) is to enhance the design and conduct of clinical studies in Rheumatic and Musculoskeletal Diseases (RMDs) with a focus on osteoarthritis (OA), a particular strength of our research community. The pain and loss of function that results from arthritis, combined with its prevalence, make it a leading cause of disability. OA is the most common form of arthritis. Efforts are urgently needed to improve the management of people with OA, as well as the many other RMDs, to reduce pain, improve function and slow or stop disease progression. Like other chronic conditions, RMDs are not single diseases but rather heterogeneous conditions consisting of multiple phenotypes that differ in their underlying pathobiological mechanisms. If not taken into consideration, these phenotypic differences result in the testing of interventions designed to address specific mechanisms of action in the “wrong” patients. Therefore, successful treatments for RMDs need to be targeted to, and tested in, specific subgroups or subtypes that share distinct underlying pathobiological, psychosocial and pain mechanisms consistent with the goal of precision medicine. Understanding and incorporating information about these phenotypes in clinical observational studies and trials will be crucial to move the field forward and is a major goal of our CCCR. Importantly, this pursuit will address the NIAMS long- range plan for clinical research which emphasizes that, “clinical characterization of disease subtypes is critical to assessment of epidemiological data and efficient design of clinical trials in these disease areas.” The proposed UNC CCCR will build on our transformative Multidisciplinary Clinical Research Center (MCRC), Mitigating the Public Health Impact of OA. Although the CCCR will have a focus on OA, the analytical methods used for phenotyping and precision medicine will also be applied to other RMDs that are strengths within our research community including RA, lupus, and vasculitis. Our goal is to optimize the design, analysis and implementation of clinical studies and trials in OA and other RMDs to advance clinical care and public health efforts targeted toward individuals with these conditions through the following aims: 1) Administrative Core: Provide leadership, oversight, coordination, evaluation, and general administrative support for all CCCR activities; 2) Methodology Core: Provide a comprehensive and integrated set of RMD-focused services to optimize the quality, efficiency and innovation of the CCCR research community that includes local, national and international members; 3) Phenotyping and Precision Medicine Resource Core: Provide services that will add value to and optimize the design and implementation of clinical studies as well as develop innovative strategies to maximize the use and success of clinical phenotyping and precision medicine in RMDs, with a focus on OA.
ABSTRACT – RESOURCE CORE The overall goal of the UNC CCCR is to enhance the design and conduct of clinical studies in Rheumatic and Musculoskeletal Diseases (RMDs) with a focus on osteoarthritis (OA), a particular strength of our research community. The Phenotyping and Precision Medicine Resource Core will provide critical services to our research community that broadly include: 1) key scientific expertise and analytic resources needed for prognostic phenotyping (predicting outcomes by specific subgroups, e.g. “progressors” versus “non-progressors”) and prescriptive phenotyping (predicting response to specific interventions) using clinical datasets, and 2) guidance and advice to investigators on phenotypic considerations (such as choice of input and outcome variables) in order to enhance the design, implementation, and interpretation of new clinical studies and trials. Like many chronic conditions, RMDs, including OA, are not single diseases but rather heterogeneous conditions consisting of multiple phenotypes that differ in their underlying pathobiological mechanisms. If not taken into consideration, these differences result in the testing of interventions designed to address specific mechanisms of action in the “wrong” patients. Successful treatments for RMDs therefore need to be targeted to, and tested in, specific subgroups or subtypes that share distinct underlying pathobiological, psychosocial and pain mechanisms, consistent with the goal of precision medicine. The Phenotyping and Precision Medicine Resource Core will work in conjunction with the Methodology Core to provide services that will greatly enhance study design and add value to a wide spectrum of ongoing, completed, and planned clinical studies through the following aims: Aim 1. Provide consultative advice and analytical services for prognostic and prescriptive phenotyping for investigators interested in defining subgroups within new or ongoing clinical studies in OA or other RMDs, including ancillary studies and studies in the planning stages. Aim 2. Apply innovative strategies for phenotyping and precision medicine by leveraging data collected in selected clinical studies from our research community, adding value to those studies, facilitating external validation and informing future studies. Aim 3. Encourage broader implementation of phenotyping and precision medicine approaches for RMDs through education and dissemination of the methodologies to local, national, and international research communities. A resource core dedicated to phenotyping and precision medicine will greatly benefit the research community that will be supported by the CCCR, make a significant impact on the field of clinical RMD research, and ultimately on the lives of people suffering from these chronic and disabling conditions.
