Collaborative for REsearch to AdvanceTMD Evidence (CREATE)

Temporomandibular disorders (TMDs) involve complex and poorly understood pathophysiological processes, limiting prevention, diagnosis, prognosis and the development or application of effective, evidence-based treatments. The Collaborative for REsearch to Advance TMD Evidence (CREATE) aims to address these critical gaps through a bidirectional approach that integrates clinical and preclinical research to identify underlying mechanisms, develop personalized therapies, and improve patient outcomes. The Administrative Core (AC) will manage CREATE’s scientific, administrative, and operational functions, ensuring alignment with NIH goals, standardizing data collection across sites, and adhering to FAIR principles for data and biospecimen management. The Bioinformatics and Data Science Core (BDSC) will employ the latest AI and machine learning techniques to analyze multi-modal data, identify TMD subtypes, implicate therapeutic targets, and establish frameworks such as common data elements (CDEs) and ontologies to enhance data integration. The Outreach, Training, and Education Core (OTEC) will expand the TMD research and clinical workforce, foster collaboration with stakeholders, and organize biannual public workshops to disseminate findings and guide the Collaborative’s efforts. At the heart of CREATE is the Deep Pain Phenotyping Project, a large-scale longitudinal study involving 1,000 TMD patients and 300 age-matched controls across multiple US clinical centers, designed to enable identification of TMD subtypes through standardized assessments and mechanistic deep phenotyping. The identification of TMD subtypes with high reliability and selectivity will facilitate diagnosis and prognosis and future clinical trials, and may suggest more effective preventive and therapeutic strategies. The clinical dataset will also inform reverse translation to preclinical studies to further elucidate mechanisms and validate therapeutic targets. By leveraging the expertise of a diverse, multidisciplinary team, CREATE seeks to bridge the gap between clinical data and preclinical insights, paving the way for improved diagnostics, treatments, and patient care in TMDs.