ABSTRACT 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 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 provide integrated functions for the clinical coordinating center (CCC), data coordinating center (DCC), and biostatistics core for the HEAL Pain ERN. Five HEAL Pain ERN trials will be selected which will require full support from the HEAL Pain ERN CCC, DCC, and biostatistics core. In addition, network-based HEAL initiative projects within the MFMU, NCORP, and PRISM will require partial select support from the HEAL Pain ERN CCC, DCC, and biostatistics core. 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 two Trial Innovation Centers. Specific Aim 2. Serve as the clinical coordinating center (CCC) for the HEAL Pain ERN trials. Specific Aim 3. Provide single IRB support for two HEAL Pain ERN trials. Specific Aim 4. Collaborate with the MFMU, PRISM, and NCORP HEAL initiative projects and provide specific assistance requested by the project investigators, NCATS, project coordinating centers, and the funding institute. 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.