The Helping to End Addiction Long-term (HEAL) initiative was developed to identify scientific solutions to the national opioid public health crisis as quickly as possible. As part of this initiative, the NIH HEAL Pain Management Effectiveness Research Network (HEAL Pain ERN) will continue to use the infrastructure of the NCATS Trial Innovation Network to provide scientific guidance and coordination of the HEAL Pain ERN Trials. Specifically, the three Trial Innovation Centers (TICs) at Duke/Vanderbilt, University of Utah, and Johns Hopkins/Tufts will continue to provide integrated functions for the clinical resource coordinating center (CRCC), data coordination resource center (DCRC), and the statistical and safety resource center (SSRC) for the HEAL Pain ERN. Two additional HEAL Pain ERN trials will be selected which will require full support from the HEAL Pain ERN CCRC, DCRC, and SSRRC. In addition, five ongoing trials supported by the HEAL ERN will continue to receive dedicated support from the resource centers. The Duke/Vanderbilt Trial Innovation Center is poised to: Specific Aim 1. Provide clinical trial leadership and expertise, assistance in study and protocol design, study implementation, and management, in collaboration with the other HEAL ERN Resource Centers, for existing and new HEAL ERN trials. Specific Aim 2. Serve as the clinical coordinating resource center (CCRC) for existing and new HEAL ERN trials. Specific Aim 3. Provide single IRB support for HEAL ERN trials for existing and new HEAL ERN trials. Through completion of these specific aims, we will harmonize the HEAL studies to achieve major innovations in trial design and execution, including: combination and reuse of valuable data, efficiencies of implementation, shared pain expertise among investigative teams, and the integration of three TICs as a cohesive unit, poised for future trial implementation.